FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Xu, GG Spivak, G Mitchell, DL Mori, T McCarrey, JR McMahan, CA Walter, RB Hanawalt, PC Walter, CA AF Xu, GG Spivak, G Mitchell, DL Mori, T McCarrey, JR McMahan, CA Walter, RB Hanawalt, PC Walter, CA TI Nucleotide excision repair activity varies among murine spermatogenic cell types SO BIOLOGY OF REPRODUCTION LA English DT Article DE aging; gamete biology; gametogenesis; spermatogenesis ID CYCLOBUTANE PYRIMIDINE DIMERS; UNSCHEDULED DNA-SYNTHESIS; GENE-EXPRESSION; ESCHERICHIA-COLI; CHILDHOOD-CANCER; GERM-CELLS; DHFR GENE; OLD MICE; DAMAGE; TRANSCRIPTION AB Germ cells perform a unique and critical biological function: they propagate the DNA that will be used to direct development of the next generation. Genetic integrity of germ cell DNA is essential for producing healthy and reproductively fit offspring, and yet germ cell DNA is damaged by endogenous and exogenous agents. Nucleotide excision repair (NER) is an important mechanism for coping with a variety of DNA lesions. Little is known about NER activity in spermatogenic cells. We expected that germ cells would be more efficient at DNA repair than somatic cells, and that this efficiency may be reduced with age when the prevalence of spontaneous mutations increases. In the present study, NER was measured in defined spermatogenic cell types, including premeiotic cells (A and B type spermatogonia), meiotic cells (pachytene spermatocytes), and postmeiotic haploid cells (round spermatids) and compared with NER in keratinocytes. Global genome repair and transcription-coupled repair subpathways of NER were examined. All spermatogenic cell types from young mice displayed good repair of (6-4) pyrimidone photoproducts, although the repair rate was slower than in primary keratinocytes. In aged mice, repair of 6-4 pyrimidone photoproducts was depressed in postmeiotic cells. While repair of cyclobutane pyrimidine dimers was not detected in spermatogenic cells or in keratinocytes, the transcribed strands of active genes were repaired with greater efficiency than nontranscribed strands or inactive genes in keratinocytes and in meiotic and postmeiotic cells; spermatogonia displayed low to moderate ability to repair cyclobutane pyrimidine dimers on both DNA strands regardless of transcriptional status. Overall, the data suggest cell type-specific NER activity during murine spermatogenesis, and our results have possible implications for germ cell aging. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio Canc Inst, San Antonio, TX 78229 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX 78957 USA. Nara Med Univ, Radioisotope Ctr, Kashihara, Nara 6340821, Japan. Univ Texas, Dept Biol, San Antonio, TX 78249 USA. SW Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78201 USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walter@uthscsa.edu OI Spivak, Graciela/0000-0001-6093-5965 FU NIA NIH HHS [AG21163, AG19316, AG24364] NR 49 TC 37 Z9 39 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2005 VL 73 IS 1 BP 123 EP 130 DI 10.1095/biolreprod.104.039123 PG 8 WC Reproductive Biology SC Reproductive Biology GA 938CY UT WOS:000229978700015 PM 15758148 ER PT J AU Kaufman, LJ Brangwynne, CP Kasza, KE Filippidi, E Gordon, VD Deisboeck, TS Weitz, DA AF Kaufman, LJ Brangwynne, CP Kasza, KE Filippidi, E Gordon, VD Deisboeck, TS Weitz, DA TI Glioma expansion in collagen I matrices: Analyzing collagen concentration-dependent growth and motility patterns SO BIOPHYSICAL JOURNAL LA English DT Article ID STOKES-RAMAN SCATTERING; MULTICELLULAR TUMOR SPHEROIDS; EXTRACELLULAR-MATRIX; CELL-MIGRATION; TRACTION FORCES; FIBRILLAR COLLAGEN; DERMAL FIBROBLASTS; CONTACT GUIDANCE; MECHANICAL FORCE; LIGHT-SCATTERING AB We study the growth and invasion of glioblastoma multiforme (GBM) in three-dimensional collagen I matrices of varying collagen concentration. Phase-contrast microscopy studies of the entire GBM system show that invasiveness at early times is limited by available collagen fibers. At early times, high collagen concentration correlates with more effective invasion. Conversely, high collagen concentration correlates with inhibition in the growth of the central portion of GBM, the multicellular tumor spheroid. Analysis of confocal reflectance images of the collagen matrices quantifies how the collagen matrices differ as a function of concentration. Studying invasion on the length scale of individual invading cells with a combination of confocal and coherent anti-Stokes Raman scattering microscopy reveals that the invasive GBM cells rely heavily on cell-matrix interactions during invasion and remodeling. C1 Columbia Univ, Dept Chem, New York, NY 10027 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA. Harvard Univ, Ctr Imaging & Mesoscale Struct, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Charlestown, MA USA. RP Kaufman, LJ (reprint author), Columbia Univ, Dept Chem, New York, NY 10027 USA. EM kaufman@chem.columbia.edu OI Filippidi, Emmanouela/0000-0002-4044-0022; Gordon, Vernita/0000-0002-5989-9378 FU NCI NIH HHS [CA 085139, CA 113004, R01 CA085139, U56 CA113004] NR 70 TC 116 Z9 117 U1 2 U2 24 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 635 EP 650 DI 10.1529/biophysj.105.061994 PG 16 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500063 PM 15849239 ER PT J AU Corbin, AS Demehri, S Griswold, IJ Wang, YH Metcalf, CA Sundaramoorthi, R Shakespeare, WC Snodgrass, J Wardwell, S Dalgarno, D Iuliucci, J Sawyer, TK Heinrich, MC Druker, BJ Deininger, MWN AF Corbin, AS Demehri, S Griswold, IJ Wang, YH Metcalf, CA Sundaramoorthi, R Shakespeare, WC Snodgrass, J Wardwell, S Dalgarno, D Iuliucci, J Sawyer, TK Heinrich, MC Druker, BJ Deininger, MWN TI In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit SO BLOOD LA English DT Article ID RECEPTOR TYROSINE KINASE; ACUTE MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; MAST-CELL DISEASE; C-KIT; WILD-TYPE; SIGNAL-TRANSDUCTION; SYSTEMIC MASTOCYTOSIS; HEMATOPOIETIC-CELLS; IMATINIB MESYLATE AB Oncogenic mutations of the Kit receptor tyrosine kinase occur in several types of malignancy. Juxtamembrane domain mutations are common in gastrointestinal stromal tumors, whereas mutations in the kinase activation loop, most commonly D816V, are seen in systemic mastocytosis and acute myelogenous leukemia. Kit activation-loop mutants are insensitive to imatinib mesylate and have been largely resistant to targeted inhibition. We determined the sensitivities of both Kit mutant classes to the adenosine triphosphate (ATP)-based inhibitors AP23464 and AP23848. In cell lines expressing activation-loop mutants, low-nM concentrations of AP23464 inhibited phosphorylation of Kit and its downstream targets Akt and signal transducer and activator of transcription 3 (STAT3). This was associated with cell-cycle arrest and apoptosis. Wild-type Kit- and juxtamembrane-mutant-expressing cell lines required considerably higher concentrations for equivalent inhibition, suggesting a therapeutic window in which cells harboring D816V Kit could be eliminated without interfering with normal cellular function. Additionally, AP23464 did not disrupt normal hematopoietic progenitor-cell growth at concentrations that inhibited activationloop mutants of Kit. in a murine model, AP23848 inhibited activation-loop mutant Kit phosphorylation and tumor growth. Thus, AP23464 and AP23848 potently and selectively target activation-loop mutants of Kit in vitro and in vivo and could have therapeutic potential against D816V-expressing malignancies. C1 Oregon Hlth & Sci Univ, Inst Canc, BMT Leukemia Ctr, Portland, OR 97239 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Deininger, MWN (reprint author), Oregon Hlth & Sci Univ, Inst Canc, BMT Leukemia Ctr, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deininge@ohsu.edu NR 42 TC 43 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 JUL 1 PY 2005 VL 106 IS 1 BP 227 EP 234 DI 10.1182/blood-2004-12-4771 PG 8 WC Hematology SC Hematology GA 940PN UT WOS:000230156500039 PM 15746079 ER PT J AU Liu, XB Yang, FM Haile, DJ AF Liu, XB Yang, FM Haile, DJ TI Functional consequences of ferroportin 1 mutations SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE ferroportin 1; hemochromatosis; mutations ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; MEMBRANE-PROTEIN STRUCTURE; CELLULAR IRON EFFLUX; GENE SLC11A3; HEREDITARY HEMOCHROMATOSIS; JUVENILE HEMOCHROMATOSIS; STRUCTURE PREDICTION; AFRICAN-AMERICANS; COMMON MUTATION; OVERLOAD AB The cellular iron exporter ferroportin I is expressed in both the duodenum and in cells of the mononuclear phagocyte system. Expression of ferroportin I protein on the cell surface is regulated by the interaction of ferroportin I with hepcidin. Hepcidin treatment of cells results in internalization and lysosomal degradation of cell surface ferroportin 1. Recently, ferroportin I mutations leading to hemochromatosis (HFE4) have been identified. HFE4 differs from classical hemochromatosis in that there is a greater amount of macrophage iron sequestration. The data presented here demonstrate that HFE4 mutations are heterogeneous in their effects on protein function. Some mutations result in loss of function with partial protein sequestration in the ER. Others are indistinguishable from native ferroportin I and have a similar ability to deplete transfected cells of iron as evidenced by activation of the iron-response proteins and cellular ferritin depletion. Significantly, all mutants appear to be unresponsive to hepcidin and do not demonstrate the expected internalization on exposure to hepcidin. The clinical phenotypes observed in patients may be secondary to cell-type-specific defects in hepcidin-mediated inhibition of ferroportin I expression. Published by Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Vet Adm Hosp, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Haile, DJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Haile@uthscsa.edu FU NHLBI NIH HHS [R01HL68842]; NIDDK NIH HHS [R01DK53079] NR 34 TC 81 Z9 83 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2005 VL 35 IS 1 BP 33 EP 46 DI 10.1016/j.bcmd.2005.04.005 PG 14 WC Hematology SC Hematology GA 946PP UT WOS:000230584800006 PM 15935710 ER PT J AU Liu, XB Nguyen, NBH Marquess, KD Yang, FM Haile, DJ AF Liu, XB Nguyen, NBH Marquess, KD Yang, FM Haile, DJ TI Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE hepcidin; ferroportin; splenic macrophage; lipopolysaccharide ID ANTIMICROBIAL PEPTIDE HEPCIDIN; IRON OVERLOAD; INFLAMMATION; ANEMIA; MICE; PROTEIN; GENE; ERYTHROPHAGOCYTOSIS; TRANSCRIPTION; IL-6 AB Acute and chronic inflammatory states are associated with many changes in intracellular iron metabolism including sequestration of iron in the mononuclear-phagocyte system (NIPS) and a decline in serum iron. Previous work in rodent models of acute inflammation has demonstrated inflammation-induced downregulation of intestinal and MPS iron exporter, ferroportin 1, mRNA and protein. In addition, these models have also demonstrated hepatic induction of mRNA of the small 25 amino acid peptide hepcidin. Hepcidin has been hypothesized to be the mediator of iron- and inflammation-induced changes in iron metabolism. The molecular details of the connection between iron metabolism, hepcidin and inflammation have become clearer with the recent finding of hepcidin-induced internalization and degradation of FPN1. The work presented here demonstrates that the lipopolysaccharide-induced splenic macrophage FPN1 mRNA downregulation is not dependent upon the action of a single cytokine such as IL-6, IL-1 or TNF-alpha because mice deficient in these pathways downregulate FPN1 normally. Furthermore, hepcidin is also synthesized in the spleen of normal mice and induced by lipopolysaccharide. Additionally, in vitro, splenic adherent cells produce hepcidin in response to lipopolysaccharide in an IL-6-dependent manner. There appear to be both probable transcriptional and post-transcriptional control of FPN1 expression by lipopolysaccharide-induced inflammation. The former effect is on mRNA expression and is independent of hepcidin, whereas the latter is IL-6- and hepcidin-dependent. Published by Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Vet Adm Hosp, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Haile, DJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Haile@uthscsa.edu FU NHLBI NIH HHS [R01HL68842]; NIDDK NIH HHS [R01DK53079] NR 19 TC 77 Z9 83 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2005 VL 35 IS 1 BP 47 EP 56 DI 10.1016/j.bcmd.2005.04.006 PG 10 WC Hematology SC Hematology GA 946PP UT WOS:000230584800007 PM 15932798 ER PT J AU Clark, DG Charuvastra, A Miller, BL Shapira, JS Mendez, MF AF Clark, DG Charuvastra, A Miller, BL Shapira, JS Mendez, MF TI Fluent versus nonfluent primary progressive aphasia: A comparison of clinical and functional neuroimaging features SO BRAIN AND LANGUAGE LA English DT Article DE aphasia; primary progressive aphasia; PET; SPECT; functional imaging; dementia; frontotemporal dementia; semantic dementia; fluency ID TEMPORAL-LOBE ATROPHY; SEMANTIC DEMENTIA; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; NEURAL BASIS; ANATOMY; SPEECH; LANGUAGE; DEGENERATION; RETRIEVAL AB To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA (Mesulam, 2001), the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n = 21) and nonfluent (n = 26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobhev Sci, Los Angeles, CA USA. Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. RP Clark, DG (reprint author), Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,3 S Neurobehv Unit,116AF, Los Angeles, CA 90073 USA. EM dgclark@mednet.ucla.edu FU NIA NIH HHS [AG19724-01A1, P01 AG019724] NR 42 TC 33 Z9 39 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JUL PY 2005 VL 94 IS 1 BP 54 EP 60 DI 10.1016/j.bandl.2004.11.007 PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 933XV UT WOS:000229667100005 PM 15896383 ER PT J AU Campos-Neto, A AF Campos-Neto, A TI What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery? SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Review DE Leishmania; Th1/Th2 paradigm; infection; vaccine; antigen discovery; adjuvant ID CELL EXPRESSION CLONING; CD8(+) T-CELLS; MAJOR INFECTION; IMMUNE-RESPONSE; DEFICIENT MICE; TRANSGENIC MICE; ANTIGEN; SUSCEPTIBILITY; DISEASE; PROTECTION AB The T helper cell type 1 (Th1) response is essential to resist leishmaniasis, whereas the Th2 response favors the disease. However, many leishmanial antigens, which stimulate a Th1 immune response during the disease or even after the disease is cured, have been shown to have no protective action. Paradoxically, antigens associated with an early Th2 response have been found to be highly protective if the Th1 response to them is generated before infection. Therefore, finding. disease-associated Th2 antigens and inducing a Th1 immune response to them using defined vaccination protocols is an interesting unorthodox alternative approach to the discovery of a leishmania vaccine. C1 Forsyth Inst, Boston, MA 02115 USA. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org NR 39 TC 25 Z9 26 U1 0 U2 2 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JUL PY 2005 VL 38 IS 7 BP 979 EP 984 DI 10.1590/S0100-879X2005000700001 PG 6 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 950AL UT WOS:000230829900001 PM 16007269 ER PT J AU Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Garrido, L AF Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Garrido, L TI Physiologic changes in breast magnetic resonance imaging during the menstrual cycle: Perfusion imaging, signal enhancement, and influence of the T1 relaxation time of breast tissue SO BREAST JOURNAL LA English DT Article DE breast; menstrual cycle; MRI ID CONTRAST-MEDIUM ENHANCEMENT; GD-DTPA; AGE; DIFFERENTIATION; RECURRENCE; DOPPLER; VOLUME; PHASE AB This study was undertaken to determine the best time during the menstrual cycle to perform dynamic breast magnetic resonance imaging (MRI). The contralateral "normal" breast of 50 premenopausal women (mean age 40.4 +/- 6.4 years, range 30-52 years) were enrolled in a protocol designed to correlate an ipsilateral suspicious breast lesion with pathology. The contralateral breast in each patient was examined with palpation and mammography prior to MRI on a 1.5T scanner using gradient echo and dynamic contrast-enhanced echo-planar without and following gadolinium diethylenetriaminepentaacetic acid (GdDTPA) injection. Pre-contrast T1 relaxation times were measured before calculating extraction flow product (EFP) maps using a multicompartmental model. T1, EFP, and enhancement were measured in the control breast on four slices centered around the nipple and recorded as a function of the phases of the menstrual cycle. Lesions or areas with focal enhancement were excluded. Analysis of variance and Fisher's tests were performed. The cyclic changes in T1 relaxation time were not significant (p > 0.2). EFP and enhancement varied significantly during the cycle (p < 0.003 and p < 0.004, respectively), with low values during the first halt of the cycle and high values during the second half. The lowest values of EFP and enhancement (5.5 +/- 2.9 ml/100 g/min and 26 +/- 17%) were observed during the proliferative phase (days 3-7), and the highest values (17 +/- 10.2 ml/100 g/min and 104 +/-28%) were observed during the secretory phase (days 21-27) (p < 0.0006 and p < 0.0008, respectively). Dynamic breast MRI should be performed during first half of the menstrual cycle (days 3-14) in order to minimize interpretative difficulties related to the uptake of gadolinium in normal breast tissue due to hormonal fluctuations during the menstrual cycle. C1 Caritas St Elizabeths Med Ctr, Dept Radiol, Div Breast Imaging, Brighton, MA 02135 USA. Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Slanetz, PJ (reprint author), Caritas St Elizabeths Med Ctr, Dept Radiol, Div Breast Imaging, 736 Cambridge St, Brighton, MA 02135 USA. EM priscilla_slanetz@cchcs.org RI Garrido, Leoncio/K-3092-2014; OI Garrido, Leoncio/0000-0002-7587-1260; Slanetz, Priscilla/0000-0003-1248-5116 NR 26 TC 76 Z9 77 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD JUL-AUG PY 2005 VL 11 IS 4 BP 236 EP 241 DI 10.1111/j.1075-122X.2005.21499.x PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 014ON UT WOS:000235489600003 PM 15982388 ER PT J AU Gombos, EC Esserman, LE Odzer-Umlas, SL Weisberg, S Poppiti, RJ AF Gombos, EC Esserman, LE Odzer-Umlas, SL Weisberg, S Poppiti, RJ TI Collagen plug metallic marker clip: Mammographic and histopathologic appearance SO BREAST JOURNAL LA English DT Editorial Material C1 Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Med Ctr, Dept Pathol & Lab Med, Miami Beach, FL 33140 USA. Mt Sinai Med Ctr, Comprehens Breast Ctr, Miami Beach, FL 33140 USA. RP Gombos, EC (reprint author), Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD JUL-AUG PY 2005 VL 11 IS 4 BP 292 EP 293 DI 10.1111/j.1075-122x.2005.21557.x PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 014ON UT WOS:000235489600017 PM 15982402 ER PT J AU Young, HS Summers, AM Read, I Fairhurst, D Plant, D Campalani, E Smith, CH Barker, JNWN Detmar, MJ Brenchley, PEC Griffiths, CEM AF Young, HS Summers, AM Read, I Fairhurst, D Plant, D Campalani, E Smith, CH Barker, JNWN Detmar, MJ Brenchley, PEC Griffiths, CEM TI Retinoid pharmacogenetics and vascular endothelial growth factor in chronic plaque psoriasis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT 85th Annual Meeting of the British-Association-of-Dermatologists CY JUL 05-08, 2005 CL Glasgow, SCOTLAND SP British Assoc Dermatologists C1 Univ Manchester, Sch Med, Hope Hosp, Dermatol Ctr, Manchester M13 9PL, Lancs, England. Manchester Royal Infirm, Manchester Inst Nephrol & Transplantat, Manchester M13 9WL, Lancs, England. St Thomas Hosp, St Johns Inst Dermatol, London, England. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Brenchley, Paul/0000-0003-1290-9919 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2005 VL 153 SU 1 BP 9 EP 10 PG 2 WC Dermatology SC Dermatology GA 955HJ UT WOS:000231216300025 ER PT J AU Torelli, GF Guarini, A Porzia, A Chiaretti, S Tatarelli, C Diverio, D Maggio, R Vitale, A Ritz, J Foa, R AF Torelli, GF Guarini, A Porzia, A Chiaretti, S Tatarelli, C Diverio, D Maggio, R Vitale, A Ritz, J Foa, R TI FLT3 inhibition in t(4;11)+ adult acute lymphoid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE FLT3; acute lymphoid leukaemia; targeted therapy; kinase inhibition; signal transduction ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE INHIBITOR; MINIMAL-RESIDUAL-DISEASE; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; GENE-EXPRESSION PROFILE; PHASE-I; MUTATIONS; ASSOCIATION; RECEPTOR AB The present study was designed to investigate, in t(4;11)+ adult lymphoid leukaemia (ALL) blast cells, the pathogenetic role of the FLT3 protein, its level of mRNA and protein expression, the degree of constitutive phosphorylation, the possible presence of mutations of the sequence, the capacity of signal transduction and the potential therapeutic role of specific inhibitors. We evaluated nine adult ALL patients carrying this translocation. The increased FLT3 mRNA levels, determined by oligonucleotide microarray analysis, was in agreement with the increased protein expression evaluated by Western blot. The protein was constitutively phosphorylated in all cases analysed. Polymerase chain reaction detected no internal tandem duplication or point mutations. The signal transduction apparatus, after stimulation with the specific ligand, was preserved. We then investigated the effect of specific FLT3 inhibition on signal transduction and survival. The PKC412 inhibitor specifically inhibited ligand-induced phosphorylation; the same inhibitor reduced the survival of leukaemic cells when compared with untreated cells. These data indicate that the FLT3 protein might play a role in this subgroup of ALL with a particularly poor prognosis. Specific inhibition of the kinase receptor must be hypothesised as an innovative therapeutic tool for t(4;11)+ ALL patients. C1 Univ Roma La Sapienza, Dept Cellular Biotechnol & Haematol, Div Haematol, I-00161 Rome, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Foa, R (reprint author), Univ Roma La Sapienza, Dept Cellular Biotechnol & Haematol, Div Haematol, Via Benevento 6, I-00161 Rome, Italy. EM rfoa@bce.uniroma1.it RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 46 TC 15 Z9 15 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2005 VL 130 IS 1 BP 43 EP 50 DI 10.1111/j.1365-2141.2005.05556.x PG 8 WC Hematology SC Hematology GA 940AN UT WOS:000230116200005 PM 15982343 ER PT J AU Heinrichs, S Berman, JN Ortiz, TM Kornblau, SM Neuberg, DS Estey, EH Look, AT AF Heinrichs, S Berman, JN Ortiz, TM Kornblau, SM Neuberg, DS Estey, EH Look, AT TI CD34(+) cell selection is required to assess HOXA9 expression levels in patients with myelodysplastic syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplastic syndrome; CD34; HOX ID BONE-MARROW-CELLS; MYELOID-LEUKEMIA; GENE-EXPRESSION AB Overexpression of HOXA9 is linked to the molecular pathogenesis of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), conferring a poor prognosis. HOXA9 expression levels were analysed in the diagnostic bone marrow (BM) samples of 13 MDS patients. HOXA9 was expressed by CD34(+) BM cells at median levels 3.1-fold higher than in CD34(-) cells from the same patient and at median levels 4.3-fold higher than in CD34(+) cells from healthy donors. These results indicate that CD34(+) cell selection is required to accurately assess the expression levels of HOXA9 and related genes in the multipotential malignant progenitor cells of MDS patients. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU NICHD NIH HHS [K12-HD00850] NR 12 TC 7 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2005 VL 130 IS 1 BP 83 EP 86 DI 10.1111/j.1365-2141.2005.05555.x PG 4 WC Hematology SC Hematology GA 940AN UT WOS:000230116200010 PM 15982348 ER PT J AU Simon, B Lee, SJ Partridge, AH Runowicz, CD AF Simon, B Lee, SJ Partridge, AH Runowicz, CD TI Preserving fertility after cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID CRYOPRESERVED OVARIAN TISSUE; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ADENOCARCINOMA IN-SITU; STAGE CERVICAL-CANCER; LONG-TERM SURVIVORS; BREAST-CANCER; CHILDHOOD-CANCER; HODGKINS-DISEASE AB In this review, the reproductive impact of treatments for several common cancers and options to maintain fertility in women and men undergoing treatment for these cancers will be discussed. The options available to any particular cancer survivor will depend on her or his age at the time of diagnosis and treatment, cancer type and primary site, stage, and type of treatment. C1 Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Univ Hosp, New York, NY 10027 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Carole & Ray Neag Comprehens Canc Ctr, Farmington, CT USA. RP Simon, B (reprint author), Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Univ Hosp, New York, NY 10027 USA. NR 131 TC 45 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL-AUG PY 2005 VL 55 IS 4 BP 211 EP 228 PG 18 WC Oncology SC Oncology GA 958YO UT WOS:000231484300005 PM 16020423 ER PT J AU Panigrahy, D Huang, S Kieran, MW Kaipainen, A AF Panigrahy, D Huang, S Kieran, MW Kaipainen, A TI PPAR gamma as a therapeutic target for tumor angiogenesis and metastasis SO CANCER BIOLOGY & THERAPY LA English DT Review DE PPAR gamma ligand; PPAR gamma antagonist; angiogenesis; growth inhibition ID ACTIVATED-RECEPTOR-GAMMA; LIGAND 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOTHELIAL-CELL MIGRATION; HUMAN BREAST-CANCER; NITRIC-OXIDE; LUNG-CANCER; IN-VITRO; COLORECTAL-CANCER; THYROID-CARCINOMA AB Peroxisome proliferator activated receptors ( PPARs) are ligand-activated transcription factors with pleiotropic effects on cell fate and metabolism. Because of its anti- proliferative, pro-apoptotic and differentiation promoting activities, PPAR gamma has been intensively evaluated as a target for anti-cancer therapy in preclinical models. However, PPAR gamma has been reported to act both as a promoter and suppressor of neoplasia, and the role of PPAR gamma activating ligands as well as antagonists in therapy remains controversial. In the past decade a new picture of tumors as a disease that involves changes in the non-cancerous tumor bed, including angiogenesis, inflammation and other stromal changes has emerged. PPAR gamma has strong anti-inflammatory and anti-angiogenic effects, extending the repertoire of potential targets of PPAR gamma ligands beyond cell autonomous mechanisms of cancer. The heterogeneous cellular targets and the biphasic effects of PPAR gamma on various pro and antitumor processes may account for the apparent paradoxical effects of PPAR g agonists. Here we review the action of PPAR gamma agonists on angiogenesis and inflammation in the context of tumorigenesis as an integrated tissue process and discuss potential explanations for the conflicting effects of PPAR g agonists on tumor progression and metastasis. Sorting out the various modes of action and defining their relative contribution in the context of tumor and host tissue as a heterogeneous target will therefore be crucial to understand the multi facetted effects of PPAR gamma. This will be paramount if the potent biological activity of PPAR gamma agonists are to be harnessed for cancer therapy. C1 Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaipainen, A (reprint author), Childrens Hosp, Vasc Biol Program, 300 Longwood Ave,Karp Res Bldg,Floor 12, Boston, MA 02115 USA. EM arja.kaipainen@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 112 TC 87 Z9 95 U1 2 U2 8 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2005 VL 4 IS 7 BP 687 EP 693 PG 7 WC Oncology SC Oncology GA 022GG UT WOS:000236042800006 PM 16082179 ER PT J AU Wei, WY Jin, JP Schlisio, S Harper, JW Kaelin, WG AF Wei, WY Jin, JP Schlisio, S Harper, JW Kaelin, WG TI The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase SO CANCER CELL LA English DT Article ID CHICKEN-EMBRYO FIBROBLASTS; GLYCOGEN-SYNTHASE KINASE-3; MULTISITE PHOSPHORYLATION; DEPENDENT PHOSPHORYLATION; PROTEIN-DEGRADATION; CYCLIN-E; IN-VIVO; MYC; TUMORIGENESIS; PROTEOLYSIS AB The c-Jun and c-Myc oncogenic transcription factors are highly unstable proteins due to polyubiquitination. Similar to c-Myc, we report here that phosphorylation of c-Jun by GSK3 creates a high-affinity binding site for the E3 ligase Fbw7, which targets c-Jun for polyubiquitination and proteasomal degradation. In keeping with this, we found that c-Jun levels were inversely related to GSK3 activity in mammalian cells that had entered the cell cycle. Importantly, phosphorylation of c-Jun by GSK3 requires a priming phosphorylation event at Ser-243. Ser-243 is mutated to phenylalanine in v-Jun and allows it to escape recognition by Fbw7. These findings explain the enhanced stability and oncogenicity of v-Jun relative to its cellular counterpart and reveal that GSK3 and Fbw7 coordinately regulate c-Jun and c-Myc. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu OI Schlisio, Susanne/0000-0002-2605-3771 FU NCI NIH HHS [R01CA76120]; NIA NIH HHS [AG11085, R01 AG011085] NR 37 TC 227 Z9 234 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2005 VL 8 IS 1 BP 25 EP 33 DI 10.1016/j.ccr.2005.06.005 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 949UO UT WOS:000230813800006 PM 16023596 ER PT J AU Ma, DQ Nutt, CL Shanehsaz, P Peng, XJ Louis, DN Kaetzel, DM AF Ma, DQ Nutt, CL Shanehsaz, P Peng, XJ Louis, DN Kaetzel, DM TI Autocrine platelet-derived growth factor-dependent gene expression in glioblastoma cells is mediated largely by activation of the transcription factor sterol regulatory element binding protein and is associated with altered genotype and patient survival in human brain tumors SO CANCER RESEARCH LA English DT Article ID COA REDUCTASE INHIBITORS; MALIGNANT GLIOMA-CELLS; IN-VIVO; FACTOR PDGF; FACTOR RECEPTORS; TRANSFORMATION; MECHANISM; THROMBOSPONDIN-1; STIMULATION; APOPTOSIS AB A complex profile of gene expression elicited by autocrine platelet-derived growth factor (PDGF) signaling was identified in U87 MG glioblastoma cells by microarray analysis. The most striking pattern observed was a PDGF-dependent activation of at least 25 genes involved with biosynthesis and/or uptake of cholesterol and isoprenoids, including mevalonate pyrophosphate decarboxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and low-density Iipoprotein receptor. Activity of the EMG-CoA synthase promoter was induced by autocrine PDGF activity as indicated by significant reductions following forced expression of dominant-negative PDGF-A (88%) or treatment with the PDGF receptor antagonist CT52923 (50%). Induction of the HMG-CoA synthase promoter required a binding site for sterol regulatory element binding proteins (SRE-BP), consistent with a key role for these transcription factors in the induction of this gene network. Neither proteolytic activation nor nuclear localization of SRE-BP was affected by disruption of the PDGF autocrine loop, indicating that PDGF signaling is required for other signaling events involved in activation of SRE-BP target genes. Analysis of an expression databank derived from human glial tumors (n = 77) identified a subgroup exhibiting a profile consistent with PDGF dependence, including increased expression of SRE-BP target genes. This subgroup displayed an absence of epidermal growth factor receptor gene amplification, decreased incidence of alletic loss of 10q, increased frequency of TP53 mutations and allelic losses of 1p and 19q, and longer patient survival. This study identifies genes associated with oncogenic activity of PDGF and provides important insights into biomarkers and therapeutic targets in malignant gliomas. C1 Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. Univ Kentucky, Dept Stat, Lexington, KY USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Canc Ctr & Neurol Serv, Dept Pathol, Boston, MA 02114 USA. RP Kaetzel, DM (reprint author), Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, 800 Rose St, Lexington, KY 40536 USA. EM dmkaetz@uky.edu RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA 57683, CA 83237]; NHLBI NIH HHS [HL 62877]; NIA NIH HHS [AG 10836] NR 53 TC 22 Z9 23 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 JUL 1 PY 2005 VL 65 IS 13 BP 5523 EP 5534 DI 10.1158/0008-5472.CAN-04-2582 PG 12 WC Oncology SC Oncology GA 940SR UT WOS:000230165000010 PM 15994924 ER PT J AU Zhao, XJ Weir, BA LaFramboise, T Lin, M Beroukhim, R Garraway, L Beheshti, J Lee, JC Naoki, K Richards, WG Sugarbaker, D Chen, F Rubin, MA Janne, PA Girard, L Minna, J Christiani, D Li, C Sellers, WR Meyerson, M AF Zhao, XJ Weir, BA LaFramboise, T Lin, M Beroukhim, R Garraway, L Beheshti, J Lee, JC Naoki, K Richards, WG Sugarbaker, D Chen, F Rubin, MA Janne, PA Girard, L Minna, J Christiani, D Li, C Sellers, WR Meyerson, M TI Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; CANCER CELL-LINES; COMPARATIVE GENOMIC HYBRIDIZATION; HIGH-RESOLUTION ANALYSIS; KINASE-4 INHIBITOR GENE; COPY-NUMBER; HETEROZYGOSITY ANALYSIS; PROGNOSTIC-SIGNIFICANCE; ACTIVATING MUTATIONS; PROSTATE-CANCER AB Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing similar to 115,000 single nucleotide polyrnorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the PTPRD locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. Highlevel amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified highlevel amplification of EGFR in three NSCLC specimens, FGFR1 in two specimens and ERBB2 and MET in one specimen each. EGFR amplification was shown to be independent of kinase domain mutational status. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA USA. Yokohama Municipal Citizens Hosp, Dept Resp Med, Yokohama, Kanagawa, Japan. Univ Texas, SW Med Ctr, Dept Internal Med & Pharmacol, Dallas, TX USA. MIT, Cambridge, MA USA. Broad Inst, Cambridge, MA USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50CA70907, 2P30 CA06516-39, T32 CA009172] NR 55 TC 242 Z9 252 U1 0 U2 4 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 JUL 1 PY 2005 VL 65 IS 13 BP 5561 EP 5570 DI 10.1158/0008-5472.CAN-04-4603 PG 10 WC Oncology SC Oncology GA 940SR UT WOS:000230165000014 PM 15994928 ER PT J AU Demou, ZN Awad, M McKee, T Perentes, JY Wang, XY Munn, LL Jain, RK Boucher, Y AF Demou, ZN Awad, M McKee, T Perentes, JY Wang, XY Munn, LL Jain, RK Boucher, Y TI Lack of telopeptides in fibrillar collagen I promotes the invasion of a metastatic breast tumor cell line SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; CARBOXYTERMINAL TELOPEPTIDE; MATRIX-METALLOPROTEINASE; GENE-EXPRESSION; MELANOMA-CELLS; CROSS-LINKING; LYSYL OXIDASE; CATHEPSIN K; MIGRATION; VIVO AB Defective fibrillar collagen polymerization in primary tumors has been correlated with increased metastasis. However, it is unclear how collagen organization influences tumor invasion. In this study, we show that collagen I polymerized without telopeptides (the flanking regions of collagen molecules) can differentially affect the three-dimensional migration of mammary carcinoma cells. MDA-MB-231 cells capable of proteolytic degradation and mesenchymal motion, invaded telopeptide-intact and telopeptide-free collagen gels to the same extent. In contrast, MDA-MB-435S cells, with typical features of amoeboid cells (poor collagenolytic activity, rounded cell morphology), were 5-fold more invasive in telopeptide-free than telopeptide-intact collagen. A fraction of the MDA-MB-435S cells that invaded telopeptide-intact or telopeptide-free collagen had a rounded morphology; however, in telopeptide-free collagen, a significant fraction of the cells switched from a rounded to elongated morphology (protrusion formation). The dynamic changes in cellular shape facilitated MDA-MB-435S locomotion through the narrow interfiber gaps, which were smaller than cell diameters. Based on the spherical morphology of MDA-MB-435S cells, we tested if the changes in cell shape and invasion were related to RhoA-ROCK activity;, GTP-bound RhoA was measured in pull-down assays. RhoA activity was 1.8-fold higher for MDA-MB-435S cells seeded on telopeptide-free than telopeptide-intact collagen. Y27632 inhibition of ROCK, a Rho effector, significantly reduced the changes in cellular morphodynamics and the invasion of MDA-MB-435S cells but did not alter the invasion of MDA-MB-231 cells. Thus, the higher RhoA activity of MDA-MB-435S cells in telopeptide-free collagen enhances the changes in cellular morphodynamics associated with motility and invasion. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. CHU Vaudois, Univ Lausanne Hosp, Dept Thorac Surg, CH-1011 Lausanne, Switzerland. RP Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, COX-7,100 Blossom St, Boston, MA 02114 USA. EM yves@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [R24 CA-85146] NR 47 TC 28 Z9 30 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2005 VL 65 IS 13 BP 5674 EP 5682 DI 10.1158/0008-5472.CAN-04-1682 PG 9 WC Oncology SC Oncology GA 940SR UT WOS:000230165000027 PM 15994941 ER PT J AU Xu, L Tong, R Cochran, DM Jain, RK AF Xu, L Tong, R Cochran, DM Jain, RK TI Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model SO CANCER RESEARCH LA English DT Article ID HUMAN OVARIAN-CARCINOMA; PROTEASE-ACTIVATED LIGAND; PDGF-B; PERICYTE RECRUITMENT; KINASE INHIBITORS; ENDOTHELIAL-CELLS; VESSEL MATURATION; FACTOR EXPRESSION; ALPHA-RECEPTOR; STROMAL CELLS AB Renal cell carcinoma is a highly malignant and often fatal disease of the kidney. It is difficult to treat, often because metastases are common at the time of presentation. platelet-derived growth factor-D (PDGF-D) is a newly discovered member of the PDGF family; its function in tumor progression is largely unknown. Here, we examined the expression level of PDGF-D in human renal cell carcinoma by immunohistochemical staining using tissue arrays. We showed that human renal cell carcinoma expresses high levels of PDGF-D protein. The human renal cell carcinoma cell line SN12-C was stably transfected with pdgf-d cDNA. Overexpression of PDGF-D in SN12-C cells promoted tumor growth, angiogenesis, and metastasis of human renal cell carcinoma in an orthotopic severe combined immunodeficient (SCID) mouse model. PDGF-D overproduction in SN12-C cells increased the proliferation and migration of mural cells in vitro and improved perivascular cell coverage in vivo. Overexpression of PDGF-D led to increased expression of angiopoietin-1 and matrix metalloproteinase-9 in tumor tissues. ShRNAi and Gleevec were used to block PDGF-D expression and PDGF receptor beta (PDGFR beta) signaling. Inhibition of PDGF-D expression by short hairpin RNA interference (shRNAi) and blockage of PDGFR beta signaling by Gleevec inhibited the growth and lung metastasis of SN12-C cells grown orthotopically in SCID mice. Thus, PDGF-D is a potential candidate for controlling the progression of metastatic renal cell carcinoma. This opens up an avenue of investigation into novel therapeutic strategies for the treatment of renal cell carcinoma, including the use of recently developed tyrosine kinase inhibitors, such as Gleevec, which inhibit PDGF activity through inhibition of its receptor tyrosine kinase. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Xu, L (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,Cox-7, Boston, MA 02114 USA. EM lei@steele.mgh.harvard.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU NCI NIH HHS [P01 CA80124, R24-CA85140] NR 54 TC 70 Z9 76 U1 0 U2 4 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 JUL 1 PY 2005 VL 65 IS 13 BP 5711 EP 5719 DI 10.1158/0008-5472.CAN-04-4313 PG 9 WC Oncology SC Oncology GA 940SR UT WOS:000230165000032 PM 15994946 ER PT J AU di Tomaso, E Capen, D Haskell, A Hart, J Logie, JJ Jain, RK McDonald, DM Jones, R Munn, LL AF di Tomaso, E Capen, D Haskell, A Hart, J Logie, JJ Jain, RK McDonald, DM Jones, R Munn, LL TI Mosaic tumor vessels: Cellular basis and ultrastructure of focal regions lacking endothelial cell markers SO CANCER RESEARCH LA English DT Article ID ADHESION MOLECULE EXPRESSION; BLOOD-VESSELS; VASCULAR-PERMEABILITY; BASEMENT-MEMBRANE; GROWTH-FACTOR; THERAPY; CANCER; ABNORMALITIES; REGRESSION; VEGF AB Endothelial cells of blood vessels in tumors may be thin, fragile, and defective in barrier function. We found previously that the endothelium of vessels in human colon carcinoma xenografts in mice is a mosaic structure. Approximately 85% of tumor vessels have uniform CD31 and/or CD105 immunoreactivity, but the remainder have focal regions that lack these common endothelial markers. The present study assessed the ultrastructure of the vessel lining and the integrity of the basement membrane in these regions. Using immunolabeling and confocal microscopy, we identified blood vessels that lacked CD31 and CD105 immunoreactivity and then analyzed the ultrastructure of these vessels by transmission electron microscopy. Eleven percent of vessels in orthotopic tumors and 24% of vessels in ectopic tumors had defects in CD31 and CD105 staining measuring on average 10.8 mu m (range, 1-41.2 mu m). Ultrastructural studies identified endothelial cells at 92% of CD31- and CD105-negative sites in orthotopic tumors and 70% of the sites in ectopic tumors. Thus, most regions of tumor vessels that lack CD31 and CD105 immunoreactivity represent attenuated endothelial cells with abnormal expression of endothelial cell markers, but some are gaps between endothelial cells. More than 80% of the defects lacked immunoreactivity for multiple basement membrane proteins. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Munn, LL (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, 100 Blossom St,Cox-7, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R01-CA82923, P01-CA80124, P50-CA90270]; NHLBI NIH HHS [P01-HL24136, R01-HL59157] NR 36 TC 57 Z9 60 U1 0 U2 4 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 JUL 1 PY 2005 VL 65 IS 13 BP 5740 EP 5749 DI 10.1158/0008-5472.CAN-04-4552 PG 10 WC Oncology SC Oncology GA 940SR UT WOS:000230165000035 PM 15994949 ER PT J AU Hanley, WD Burdick, MM Konstantopoulos, K Sackstein, R AF Hanley, WD Burdick, MM Konstantopoulos, K Sackstein, R TI CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity SO CANCER RESEARCH LA English DT Article ID P-SELECTIN; ADHESION; CANCER; METASTASIS; BINDING; VARIANT; FLOW; GLYCOPROTEINS; HYALURONAN; EXPRESSION AB Metastasis of circulating tumor cells requires a multistep cascade of events initiated by adhesion of tumor cells to the vascular endothelium of involved tissues. This process occurs under the forces of blood flow and is promoted by adhesion molecules specialized to interact under shear conditions. The endothelial molecule E-selectin is a major mediator of these adhesive events, and there is strong evidence that E-selectin receptor-ligand interactions contribute to the formation of metastasis. However, little is known about the identity of E-selectin ligand(s) expressed on cancer cells. To address this issue, we did SDS-PAGE analysis of membrane proteins, metabolic inhibition studies, and blot rolling assays of LS174T, a colon carcinoma cell line known to interact with E-selectin under physiologic flow conditions. Our studies show that LS174T cells express the hematopoictic cell E/L-selectin (HCELL) glycoform of CD44, which functions as a high-affinity E-selectin glycoprotein ligand on these cells. However, in contrast to the HCELL glycoform on human hematopoietic progenitor cells, which expresses carbohydrate-binding determinant(s) for E-selectin primarily on N-glycans of standard CD44, the relevant determinant(s) on LS174T cells is expressed on O-glycans and is predominantly found on variant isoforms of CD44 (CD44v). Our finding that tumor-associated CD44 splice variant(s) express E-selectin ligand activity provides novel perspectives on the biology of CD44 in cancer metastasis. C1 Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr,Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr,Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM kkonsta1@jhu.edu RI Konstantopoulos, Konstantinos/A-7045-2011 FU NCI NIH HHS [R01 CA 101135]; NHLBI NIH HHS [R01 HL073714, R01 HL60528] NR 34 TC 67 Z9 71 U1 0 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 JUL 1 PY 2005 VL 65 IS 13 BP 5812 EP 5817 DI 10.1158/0008-5472.CAN-04-4557 PG 6 WC Oncology SC Oncology GA 940SR UT WOS:000230165000043 PM 15994957 ER PT J AU Detwiller, KY Fernando, NT Segal, NH Ryeom, SW D'Amore, PA Yoon, SS AF Detwiller, KY Fernando, NT Segal, NH Ryeom, SW D'Amore, PA Yoon, SS TI Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMAS; TUMOR ANGIOGENESIS; VEGF; SIRNA; CLASSIFICATION; MUTATIONS; STABILITY; PATTERNS; THERAPY; SUBTYPE AB Vascular endothelial cell growth factor A (VEGF-A) and hypoxia play important roles in tumor angiogenesis. VEGF-A gene expression is up-regulated in tumors under hypoxic conditions, yet it is unclear how such up-regulation will affect the efficacy of RNA interference strategies targeting VEGF-A. Four potential short interfering RNA (siRNA) sequences for the VEGF-A gene were cloned into expression plasmids and transfected into HT1080 human fibrosarcoma cells. Stable transfection of these plasmids decreased VEGF-A mRNA levels and protein secretion by up to 99%. Our analysis of > 100 hypoxia-related genes using oligonucleotide microarrays of 38 human sarcoma samples and 14 normal tissues identified distinctly different patterns of expression between sarcomas and normal tissues as assessed by hierarchical clustering analysis. Numerous hypoxia-related genes were significantly up-regulated in sarcomas including hypoxia-inducible factor 1 alpha- (HIF-1 alpha). Exposure of wild-type HT1080 cells to 1% hypnxia resulted in HIF-1 alpha up-regulation and a 74% increase in VEGF-A secretion as compared with secretion under normoxic conditions. Surprisingly, stable cell lines expressing VEGF-A siRNAs silenced VEGF-A expression equally well in hypoxia and normoxia. S.c. injection of cells with VEGF-A siRNAs into athymic nude mice led to slower-growing tumors, decreased blood vessel density, and greater apoptosis when compared with controls. Immunofluorescence analysis of tumor sections revealed areas of HIF-1 alpha nuclear expression, suggesting areas of hypoxia, in both control tumors and VEGF-suppressed tumors. We conclude that hypoxia plays an important role in human sarcomas but hypoxic up-regulation of VEGF-A expression does not attenuate the efficacy of VEGF-A RNA interference. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. Boston Childrens Hosp, Dept Surg, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org FU NCI NIH HHS [5 K12 CA 87723-03] NR 38 TC 90 Z9 96 U1 0 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 JUL 1 PY 2005 VL 65 IS 13 BP 5881 EP 5889 DI 10.1158/0008-5472.CAN-04-4078 PG 9 WC Oncology SC Oncology GA 940SR UT WOS:000230165000052 PM 15994966 ER PT J AU Tai, YT Li, XF Tong, X Santos, D Otsuki, T Catley, L Tournilhac, O Podar, K Hideshima, T Schlossman, R Richardson, P Munshi, NC Luqman, M Anderson, KC AF Tai, YT Li, XF Tong, X Santos, D Otsuki, T Catley, L Tournilhac, O Podar, K Hideshima, T Schlossman, R Richardson, P Munshi, NC Luqman, M Anderson, KC TI Human anti-CD40 antagonist antibody triggers significant antitumor activity against human multiple myeloma SO CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; GROWTH-FACTOR SECRETION; MARROW STROMAL CELLS; MONOCLONAL-ANTIBODY; PLASMA-CELLS; THERAPEUTIC APPLICATIONS; PHASE-II; IN-VITRO; B-CELLS; RITUXIMAB AB Monoclonal antibodies (mAb) directed against lineage-specific B-cell antigens have provided clinical benefit for patients with hematologic malignancies, but to date no antibody-mediated immunotherapy is available for multiple myeloma. In the present study, we assessed the efficacy of a fully human antiCD40 mAb CHIR-12.12 against human multiple myeloma cells. CHIR-12.12, generated in XenoMouse mice, binds to CD138-expressing multiple myeloma lines and freshly purified CD138-expressing cells from > 80% multiple mycloma patients, as assessed by flow cytometry. Importantly, CHIR-12.12 abrogates CD40L-induced growth and survival of CD40-expressing patient multiple mycloma cells in the presence or absence of bone marrow stromal cells (BMSC), without altering constitutive multiple myeloma cell proliferation. Immunoblotting analysis specifically showed that PI3-K/AKT, nuclear factor-KB (NF-KB), and extracellular signal-regulated kinase activation induced by CD40L (5 mu g/mL) was inhibited by CHIR-12.12 (5 mu g/mL). Because CD40 activation induces multiple myeloma cell adhesion to both fibronectin and BMSCs, we next determined whether CHIR-12.12 inhibits this process. CHIR-12.12 decreased CD40L-induced multiple myeloma cell adhesion to fibronectin and BMSCs, whereas control human IgG1 did not. Adhesion of multiple myeloma cells to BMSCs induces interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, and treatment of multiple mycloma cells with CD40L further enhanced adhesion-induced cytokine secretion; conversely, CHIR-12.12 blocks CD40L-enhanced IL-6 and VEGF secretion in cocultures of multiple myeloma cells with BMSCs. Finally, CHIR-12.12 triggered lysis of multiple myeloma cells via antibody-dependent cellular cytotoxicity (ADCC) but did not induce ADCC against CD40-negative multiple myeloma cells, confirming specificity against CD40-expressing multiple myeloma cells. These results provide the preclinical rationale for clinical trials of CHIR-12.12 to improve patient outcome in multiple myeloma. C1 Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst,Jerome Lipper Multiple Myel, Boston, MA 02115 USA. Kawasaki Med Univ, Dept Hyg, Okayama, Japan. Chiron Corp, Emeryville, CA 94608 USA. RP Anderson, KC (reprint author), Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst,Jerome Lipper Multiple Myel, M557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [P01-78378, R0-1 50947] NR 36 TC 99 Z9 106 U1 0 U2 4 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 JUL 1 PY 2005 VL 65 IS 13 BP 5898 EP 5906 DI 10.1158/0008-5472.CAN-04-4125 PG 9 WC Oncology SC Oncology GA 940SR UT WOS:000230165000054 PM 15994968 ER PT J AU vanSonnenberg, E Goodacre, BW Wittich, GR Ali, S Silverman, SG Shankar, S Tuncali, K AF vanSonnenberg, E Goodacre, BW Wittich, GR Ali, S Silverman, SG Shankar, S Tuncali, K TI Interventional radiology strategies in the treatment of pseudomyxoma peritonei SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE pseudomyxoma peritonei; interventional radiology; catheters; abscess, treatment; ascites; ovarian carcinoma ID MANAGEMENT AB Purpose: To describe percutaneous maneuvers to treat the unusual entity symptomatic pseudomyxoma peritonei (PMP). Methods: Four patients with PMP were treated by interventional radiology techniques that included large catheters (2030 Fr) alone (n = 3), multiple catheters (n = 4), and dextran sulfate as a catalytic agent through smaller catheters (n = 1). The causes of the PMP were tumors in the ovary (2 patients), appendix (I patient), and colon (I patient). Each patient previously had undergone at least two operations to remove the PMP, and all patients had symptomatic recurrence. An in vitro analysis of catalytic agents also was performed. Results: All four patients improved symptomatically. Followup CT scans demonstrated marked reduction of PMP material in all cases. One patient underwent another interventional radiology session 5 months after the first; the other three patients had no recurrence of symptoms. One patient had reversible hypotension 2 hr after the procedure. The amount of material removed varied from 3 to 6 L. Conclusion: These interventional radiology techniques were effective and safe for PMP and suggest options for this difficult medical and surgical problem. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Victoria Gen Hosp, Dept Radiol, Victoria, BC V8Z 6R5, Canada. Bayshore Med, Alliance Radiol Consultants, Pasadena, TX 77504 USA. Univ Texas, Med Branch, Dept Radiol, Galveston, TX 77755 USA. Univ Massachusetts, Dept Radiol, Worcester, MA 01655 USA. RP vanSonnenberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. EM ericvansonnenberg@yahoo.com NR 13 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUL-AUG PY 2005 VL 28 IS 4 BP 490 EP 494 DI 10.1007/s00270-003-4084-9 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 956KC UT WOS:000231297600016 PM 16034657 ER PT J AU Hayase, M Kawase, Y Yoneyama, R Hoshino, K McGregor, J MacNeill, BD Lowe, HC Burkhoff, D Boekstegers, P Hajjar, RJ AF Hayase, M Kawase, Y Yoneyama, R Hoshino, K McGregor, J MacNeill, BD Lowe, HC Burkhoff, D Boekstegers, P Hajjar, RJ TI Catheter-based ventricle-coronary vein bypass SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Review DE coronary vein; left ventricle; coronary bypass; catheterization ID UTILIZING RADIOACTIVE MICROSPHERES; SELECTIVE ARTERIALIZATION; MYOCARDIAL-ISCHEMIA; VENOUS SYSTEM; BLOOD-FLOW; PERFUSION; ANATOMY AB The goal of this study was to investigate the feasibility of a catheter-based ventricle-tocoronary vein bypass (VPASS) in order to achieve retrograde myocardial perfusion by a conduit (VSTENT) from the left ventricle (LV) to the anterior interventricular vein (AIV). Percutaneous coronary venous arterialization has been proposed as a potential treatment strategy for otherwise untreatable coronary artery disease. In an acute setting, the VSTENT implant was deployed percutaneously using the VPASS procedure in five swine. Coronary venous flow and pressure patterns were measured before and after VSTENT implant deployment with and without AIV and left anterior descending artery (LAD) occlusion. In a separate chronic pilot study, the VPASS procedure was completed on two animals that had a mid-LAD occlusion or LAD stenosis. At day 30 post-VPASS procedure, left ventriculography and magnetic resonance imaging (MRI) were performed to assess the patency and myocardial viability of the VSTENT implants. Pre-VSTENT implantation, the mid-AIV systolic wedge pressure was significantly lower than LV systolic pressure during AIV blockage (46 +/- 19 vs. 90 +/- 16 mm Hg; P < 0.01). The VSTENT implant deployment was performed without complication and achieved equalization of the AIV and LV systolic pressures and creation of retrograde flow in the distal AIV (maximal flow velocity: 37 +/- 7 cm/sec). At day 30 post-VPASS procedure, left ventriculography showed VSTENT implant patency. MRI perfusion images demonstrated myocardial viability even with an LAD occlusion. Coronary retrograde perfusion using the VPASS procedure is feasible and may represent a potential technique for end-stage myocardial ischemia. Catheter (c) 2005Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Lab Integrat Physiol & Imaging,Div Cardio, Boston, MA 02114 USA. Columbia Univ, Dept Med & Surg, New York, NY USA. Grosshadern Univ Hosp, Dept Internal Med 1, Munich, Germany. RP Hayase, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Lab Integrat Physiol & Imaging,Div Cardio, 55 Fruit St,Bulfinch 161, Boston, MA 02114 USA. EM mhayase@partners.org RI Burkhoff, Daniel/D-7674-2011 NR 17 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL PY 2005 VL 65 IS 3 BP 394 EP 404 DI 10.1002/ccd.20312 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 940HE UT WOS:000230133500013 PM 15822113 ER PT J AU Wagers, AJ AF Wagers, AJ TI Stem cell grand SLAM SO CELL LA English DT Editorial Material ID BONE-MARROW NICHE; HEMATOPOIETIC STEM; SIZE AB Stem cells in both embryonic and adult tissues are defined by their unique ability to balance self-renewal and differentiation such that mature cells necessary for tissue function can be generated and replaced without depletion of the stem cell pool. In this issue of Cell, Kiel et al. (2005) report a major step forward for studying the mechanisms and regulation of such stem cell fate decisions in the blood-forming (hematopoietic) system by providing a simple and broadly applicable method to isolate these cells and to visualize them in their normal environment. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 13 TC 15 Z9 15 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 1 PY 2005 VL 121 IS 7 BP 967 EP 970 DI 10.1016/j.cell.2005.06.017 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 944RZ UT WOS:000230448000003 PM 15989946 ER PT J AU Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, MR Stokes, N Murphy, MM Appella, E Alt, FW AF Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, MR Stokes, N Murphy, MM Appella, E Alt, FW TI Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress SO CELL METABOLISM LA English DT Article ID ARF TUMOR-SUPPRESSOR; DOUBLE-STRAND BREAKS; CELLULAR SENESCENCE; TRANSCRIPTION FACTORS; PREMATURE SENESCENCE; CALORIE RESTRICTION; ONCOGENIC RAS; GENE-PRODUCT; G(1) CONTROL; INK4A LOCUS AB The Saccharomyces cerevisiae chromatin silencing factor Sir2 suppresses genomic instability and extends replicative life span. In contrast, we find that mouse embryonic fibroblasts (MEFs) deficient for SIRT1, a mammalian Sir2 homolog, have dramatically increased resistance to replicative senescence. Extended replicative life span of SIRT1-deficient MEFs correlates with enhanced proliferative capacity under conditions of chronic, sublethal oxidative stress. In this context, SIRT1-deficient cells fail to normally upregulate either the p19(ARF) senescence regulator or its downstream target p53. However, upon acute DNA damage or oncogene expression, SIRT1-deficient cells show normal p19(ARF) induction and cell cycle arrest. Together, our findings demonstrate an unexpected SIRT1 function in promoting replicative senescence in response to chronic cellular stress and implicate p19(ARF) as a downstream effector in this pathway. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 64 TC 172 Z9 188 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2005 VL 2 IS 1 BP 67 EP 76 DI 10.1016/j.cmet.2005.06.007 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 949EJ UT WOS:000230767400010 PM 16054100 ER PT J AU Mularski, RA Heine, CE Osborne, ML Ganzini, L Curtis, JR AF Mularski, RA Heine, CE Osborne, ML Ganzini, L Curtis, JR TI Quality of dying in the ICU - Ratings by family members SO CHEST LA English DT Article DE critical care; death; end-of-life care; ethics; intensive care; outcome and process assessment (health care); quality of health care; rating; research, clinical; terminal care ID END-OF-LIFE; ILL HOSPITALIZED-PATIENTS; INTENSIVE-CARE-UNIT; OUTCOMES; DEATH; PREFERENCES; EXPERIENCE; SUPPORT; SYSTEM; OLDER AB Study objectives: To explore the quality of the dying experience and associations to higher quality ratings for people who died in an ICU. Design: Retrospective study using medical record review and surveys of family members with the Quality of Dying and Death (QODD) instrument. Setting: Four ICUs affiliated with a university and a Veterans Affairs Medical Center. Participants: Ninety-four family members of 38 ICU decedents. Measurements and results: We explored associations between components of the ICU experience and the overall rating of the quality of the dying experience. Overall, family members reported that symptoms were poorly controlled: pain under control most or all of the time in 47%, and breathing comfortably most or all of the time in 3% of patients. Families expressed a moderate and variable view of the quality of dying resulting in an overall ICU QODD score of 60 +/- 14 (on a scale of 0 to 100) [mean +/- SD]. Higher ICU QODD scores were associated with control of pain (r = 0.42, p = 0.009), control of events (r = 0.62, p < 0.001), a "preparation for death" aspect of the dying experience-feeling at peace with dying (r = 0.69, p < 0.001), and a "whole-person concern- keeping one's dignity and self-respect (r = 0.50, p < 0.001). Conclusions: After adjusting for symptom and personal care scores, certain whole-person and preparation-for-death aspects of the dying process, and not aggressiveness of end-of-life care, remained the most associated to quality ratings. While future research should explore the important predictors of quality of dying in the ICU, this study suggests that care at the end of life in the ICU include not only managing pain, but also supporting dignity, respect, and peace, and maximizing patient control. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Virginia Hlth SYst, Dept Emergency Med, Charlottesville, VA USA. Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR USA. Portland Vet Affairs Med Ctr, Dept Psychiat, Portland, OR USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Harborview Med Ctr, Seattle, WA USA. RP Mularski, RA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Mailcode 111G, Los Angeles, CA 90073 USA. EM Richard.Mularski@med.va.gov FU NCRR NIH HHS [5M01 RR 00334] NR 29 TC 77 Z9 84 U1 4 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2005 VL 128 IS 1 BP 280 EP 287 DI 10.1378/chest.128.1.280 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 945VN UT WOS:000230530500045 PM 16002947 ER PT J AU Beresin, EV Olson, CK AF Beresin, EV Olson, CK TI Child psychiatry and the media - Preface SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mental Hlth & Media,Dept Psychiat, Waltham, MA 02452 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang 812,15 Parkman St, Boston, MA 02114 USA. EM eberesin@partners.org; colson@hms.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP XVII EP XIX DI 10.1016/j.chc.2005.03.002 PG 3 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500002 ER PT J AU Fremont, WP Pataki, C Beresin, EV AF Fremont, WP Pataki, C Beresin, EV TI The impact of terrorism on children and adolescents: Terror in the skies, terror on television SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; ABUSED PRESCHOOL-CHILDREN; SCHOOL-AGE-CHILDREN; NATURAL DISASTER; MENTAL-HEALTH; FOLLOW-UP; TRAUMATIC EVENTS; REFUGEE CHILDREN; RISK-FACTORS; PSYCHOLOGICAL REACTIONS AB Terrorist attacks and their aftermath have had a powerful impact on children and their families. Media and television exposure of terrorist events throughout the world has increased during the past few years. There is increasing concern about the effects of this exposure on children who witness these violent images. To develop a proactive and strategic response to reactions of fear, clinicians, educators, and policy makers must understand the psychologic effects of media coverage of terrorism on children. Previous research has focused on media coverage of criminal violence and war. Recent studies have examined the effect of remote exposure of terrorist attacks and have shown a significant clinical impact on children and families. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, McLean Hosp, Dept Psychiat, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mental Hlth & Media, Boston, MA 02114 USA. RP Fremont, WP (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM fremontw@upstate.edu NR 128 TC 13 Z9 13 U1 9 U2 21 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 429 EP + DI 10.1016/j.chc.2005.02.001 PG 24 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500006 PM 15936667 ER PT J AU Wiseman, CV Sunday, SR Becker, AE AF Wiseman, CV Sunday, SR Becker, AE TI Impact of the media on adolescent body image SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID DISORDER PREVENTION PROGRAMS; MEXICAN-AMERICAN WOMEN; EATING DISTURBANCE; SELF-ESTEEM; CULTURAL EXPECTATIONS; BULIMIC SYMPTOMS; AFRICAN-AMERICAN; HEALTH-EDUCATION; UNITED-STATES; RISK-FACTORS AB The mass media have become a powerful force throughout the world and strongly influence how people see themselves and others. This is particularly true for adolescents. This article discusses how the media affect body image and self-esteem and why the media seem to have such strong effects on adolescents. The differences in responses to the media in adolescents of different ethnic, racial, and cultural backgrounds are discussed. Although this article focuses primarily on teenage girls, the data for adolescent boys is reviewed as well. Finally, this article discusses possible ways to help adolescents become more active viewers of the media and help prevent the decrease in body esteem that so often occurs during adolescence. C1 Trinity Coll, Dept Psychol, Hartford, CT 06106 USA. N Shore Univ Hosp, Dept Psychiat, Manhasset, NY 11030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02114 USA. RP Wiseman, CV (reprint author), Trinity Coll, Dept Psychol, 300 Summit St, Hartford, CT 06106 USA. EM Claire.wiseman@trincoll.edu FU CMHS SAMHSA HHS [U79 SM54251]; NIMH NIH HHS [5K23MH068575-02, R01MH602642] NR 129 TC 11 Z9 13 U1 10 U2 41 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 453 EP + DI 10.1016/j.chc.2005.02.008 PG 21 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500007 PM 15936668 ER PT J AU Gelfond, HS Salonius-Pasternak, DE AF Gelfond, HS Salonius-Pasternak, DE TI The play's the thing: A clinical-developmental perspective on video games SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PROSOCIAL BEHAVIOR; REAL-LIFE; AGGRESSION; CHEMOTHERAPY; ADOLESCENTS; CHILDREN; VIOLENCE; DISTRACTION; DIMENSIONS; CHILDHOOD AB In this article, computer and video games are discussed as electronic play. Major perspectives on play and salient developmental issues are presented, along with similarities and differences between electronic play and other types of play. The authors consider possible benefits and risks associated with this type of play, with particular attention paid to cognitive and socioemotional development. Recommendations for clinicians in their work with children, adolescents, and parents are discussed, as are future directions for research. C1 Harvard Univ, Sch Med, Ctr Mental Hlth & Media, Waltham, MA 02452 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Salonius-Pasternak, DE (reprint author), Harvard Univ, Sch Med, Ctr Mental Hlth & Media, 271 Waverley Oaks Rd, Waltham, MA 02452 USA. EM dsaloniuspasternak@partners.org NR 73 TC 7 Z9 7 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 491 EP + DI 10.1016/j.chc.2005.02.010 PG 19 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500009 PM 15936670 ER PT J AU Villani, VS Olson, CK Jellinek, MS AF Villani, VS Olson, CK Jellinek, MS TI Media literacy for clinicians and parents SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID REDUCING CHILDRENS TELEVISION; RANDOMIZED CONTROLLED-TRIAL; VIOLENT VIDEO GAMES; AGGRESSIVE-BEHAVIOR; PRESCHOOL-CHILDREN; COMPUTER USE; ADOLESCENTS; EXPOSURE; RATINGS; YOUTH AB Families and children are in the midst of a media revolution. Television, Internet access, instant messaging, cell phones, and interactive video games are delivering more information for more hours than ever in history. Exposure is occurring at younger and younger ages, often without parental oversight or interpretation. The impact on children is just beginning to be studied. Does media exposure prepare children for the world in which they live or deprive them of critical developmental opportunities? Does the steady display of violence contribute to violent behavior? This article presents a developmental context, discusses the research conducted to date, reviews the recommendations of major organizations, and tries to take a balanced perspective in the midst of a rising tide of media, technology; commercialism, and controversy. C1 Johns Hopkins Univ, Sch Programs, Kennedy Krieger Inst, Sch Med,Dept Psychiat, Baltimore, MD 21231 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mental Hlth & Media,Dept Psychiat, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Villani, VS (reprint author), Johns Hopkins Univ, Sch Programs, Kennedy Krieger Inst, Sch Med,Dept Psychiat, 1750 E Fairmount Ave, Baltimore, MD 21231 USA. EM villani@kennedykrieger.org NR 77 TC 9 Z9 9 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 523 EP + DI 10.1016/j.chc.2005.03.001 PG 32 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500011 PM 15936672 ER PT J AU Falzone, RL Hall, S Beresin, EV AF Falzone, RL Hall, S Beresin, EV TI How and why for the camera-shy: Using digital video in psychiatry SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PSYCHOTHERAPY; COMPETENCES; FEEDBACK AB Videotaping and digital editing (desktop video) provide a therapist with compelling material that can be used for therapy with patients, for teaching and professional presentation, and for therapist development. Despite these advantages, many clinicians are reluctant to record their work for reasons that include self-consciousness on the part of the therapist or patient, concerns about negative effects of videotaping on the session, concerns about confidentiality and legal liability, and lack of familiarity with the process of videotaping and the equipment involved. Understanding the benefits, concerns, and basic process involved in video recording and editing should reduce clinician apprehension and encourage more widespread use of this powerful clinical medium. C1 Massachusetts Gen Hosp, McLean Hosp, Dept Psychiat, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mental Hlth & Media, Boston, MA 02114 USA. RP Falzone, RL (reprint author), Massachusetts Gen Hosp, McLean Hosp, Dept Psychiat, Div Child & Adolescent Psychiat, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM mail@rfalzone.info NR 15 TC 4 Z9 4 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 603 EP + DI 10.1016/j.chc.2005.02.006 PG 11 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500015 PM 15936676 ER PT J AU Olson, CK Kutner, LA AF Olson, CK Kutner, LA TI Media outreach for child psychiatrists SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DEFEAT DEPRESSION CAMPAIGN; MENTAL-ILLNESS; DISORDERS; ATTITUDES; PEOPLE AB Psychiatrists have mixed feelings about working with the mass media. There are many reasons to respond to reporters or proactively reach out to the media, including reducing stigma and other barriers to seeking and complying with treatment, and counteracting media misinformation and distortion. This article addresses ways to increase positive outcomes when psychiatrists respond to calls from reporters, make proactive efforts to influence behaviors or policies, or take advantage of breaking news to educate reporters and the public. The article also reviews examples of planned media campaigns. C1 Harvard Univ, Sch Med, Ctr Mental Hlth & Media, Massachusetts Gen Hosp,Dept Psychiat, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Olson, CK (reprint author), Harvard Univ, Sch Med, Ctr Mental Hlth & Media, 271 Waverley Oaks Rd,Suite 204, Waltham, MA 02452 USA. EM colson@hms.harvard.edu NR 34 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2005 VL 14 IS 3 BP 613 EP + DI 10.1016/j.chc.2005.02.011 PG 12 WC Psychiatry SC Psychiatry GA 939TO UT WOS:000230095500016 PM 15936677 ER PT J AU Howe, N Petrakos, H Rinaldi, CM LeFebvre, R AF Howe, N Petrakos, H Rinaldi, CM LeFebvre, R TI "This is a bad dog, you know...": Constructing shared meanings during sibling pretend play SO CHILD DEVELOPMENT LA English DT Article ID INTERNAL STATE LANGUAGE; INDIVIDUAL-DIFFERENCES; CONFLICT; FRIENDS; PERSPECTIVE; CHILDHOOD; FEELINGS; CHILDREN; BELIEFS; QUALITY AB The construction of shared meanings in play, pretense enactment, internal state language, and sibling relationship quality were investigated in 40 kindergarteners with an older (M age = 7.10 years) or younger ( M age = 3.6 years) sibling. Dyadic strategies to construct shared meanings ( e. g., extensions, building on) were positively associated with frequency of pretense and internal state language. Developmental differences indicated that older dyads used more shared meaning strategies, whereas younger dyads engaged in nonmaintenance behaviors (i. e., disruptions to flow of play). Furthermore, firstborn kindergarteners used more nonmaintenance behaviors, whereas second-born kindergarteners extended partner's ideas. Findings highlight the sibling relationship as a context for illuminating social understanding and relationship dynamics during pretend play. C1 Concordia Univ, Dept Educ, Montreal, PQ H3G 1M8, Canada. Univ Alberta, Edmonton, AB T6G 2M7, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Howe, N (reprint author), Concordia Univ, Dept Educ, 1455 Maisonneuve W, Montreal, PQ H3G 1M8, Canada. EM nina.howe@education.concordia.ca NR 48 TC 21 Z9 22 U1 9 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JUL-AUG PY 2005 VL 76 IS 4 BP 783 EP 794 DI 10.1111/j.1467-8624.2005.00877.x PG 12 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 945HK UT WOS:000230493400002 PM 16026496 ER PT J AU Starren, J Tsai, C Bakken, S Aidala, A Morin, PC Hilliman, C Weinstock, RS Goland, R Teresi, J Shea, S AF Starren, J Tsai, C Bakken, S Aidala, A Morin, PC Hilliman, C Weinstock, RS Goland, R Teresi, J Shea, S CA IDEATel Consortium TI The role of nurses in installing telehealth technology in the home SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE telemedicine; nursing; medical informatics; technology ID TELEMEDICINE; INFORMATICS; IMPACT AB Home telehealth involves the use of video conferencing or remote monitoring equipment in patients' homes. The installation of hardware and training of patients has historically been performed by nurses, typically RNs. This article examines the experience of RNs as telehealth installers in the Informatics for Diabetes Education and Telemedicine (IDEATel) project, where RNs were responsible for the installation of the Home Telemedicine Units (HTUs) and for training patients in the use of the HTUs, blood pressure cuffs, and fingerstick glucose meters. Average installation and training time was 166 minutes (SD 51 min). Structured interviews with RN installers revealed that patient education and training accounted for roughly two thirds of the in-home time. Technology-related problems, especially those related to telecommunications, were the primary cause of installation difficulties. Thematic analysis of installer interviews identified eight major themes and confirmed the importance of both clinical and technical knowledge during the telehealth installation process. C1 Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. VA Med Ctr, Syracuse, NY USA. Naomi Berrie Diabet Ctr, New York, NY USA. Hebrew Home Aged, Riverdale, NY USA. New York Psychiat Inst, New York, NY USA. RP Starren, J (reprint author), Columbia Univ, Dept Biomed Informat, 622W 168th St, New York, NY 10032 USA. EM starren@dbmi.columbia.edu NR 32 TC 12 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD JUL-AUG PY 2005 VL 23 IS 4 BP 181 EP 189 DI 10.1097/00024665-200507000-00004 PG 9 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 948WF UT WOS:000230745700001 PM 16027532 ER PT J AU Bertagnolli, MM AF Bertagnolli, MM TI Radioimmunotherapy for colorectal cancer SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID FRACTIONATED RADIOIMMUNOTHERAPY; TRIAL C1 Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. Womens Hosp Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 6 Z9 6 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 JUL 1 PY 2005 VL 11 IS 13 BP 4637 EP 4638 DI 10.1158/1078-0432.CCR-05-0485 PG 2 WC Oncology SC Oncology GA 944BQ UT WOS:000230400300001 PM 16000553 ER PT J AU Ozen, M Ittmann, M AF Ozen, M Ittmann, M TI Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID 14-3-3 PROTEIN-BINDING; DIFFERENTIAL EXPRESSION; OVEREXPRESSION; KINASE; PHOSPHORYLATION; CELLS; CHK1; PROGRESSION; ACTIVATION AB Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G(2)-M transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25 C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Ittmann, M (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Serv, 2002 Holocombe Blve, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU NCI NIH HHS [P50CA058204] NR 32 TC 37 Z9 41 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 JUL 1 PY 2005 VL 11 IS 13 BP 4701 EP 4706 DI 10.1158/1078-0432.CCR-04-2551 PG 6 WC Oncology SC Oncology GA 944BQ UT WOS:000230400300012 PM 16000564 ER PT J AU Golemovic, M Verstovsek, S Giles, F Cortes, J Manshouri, T Manley, PW Mestan, J Dugan, M Alland, L Griffin, JD Arlinghaus, RB Sun, T Kantarjian, H Beran, M AF Golemovic, M Verstovsek, S Giles, F Cortes, J Manshouri, T Manley, PW Mestan, J Dugan, M Alland, L Griffin, JD Arlinghaus, RB Sun, T Kantarjian, H Beran, M TI AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; IMMUNODEFICIENT MOUSE MODEL; TYROSINE KINASE; CYTOGENETIC RESPONSES; MESYLATE THERAPY; CELL-LINES; STI571 RESISTANCE; SCID MICE; PHASE AB Resistance to or intolerance of imatinib in patients with Philadelphia chromosome - positive chronic myelogenous leukemia (CML) has encouraged the development of more potent Bcr-Abl inhibitors. AMN107 is a novel, orally bioavailable ATP-competitive inhibitor of Bcr-Abl. The effects of AMN107 were compared with those of imatinib on imatinib-sensitive (KBM5 and KBM7) and imatinib-resistant CML cell lines (KBM5-ST1571(R1.0) and KBM7-ST1571(R1.0)). Compared with the antiproliferative activity of imatinib, AMN107 was 43 times more potent in KBM5 (IC50 of 11.3 versus 480.5 nmol/L) and 60 times more potent in KBM7 (IC50 of 4.3 versus 259.0 nmol/L) cells, IC50 for AMN107 and imatinib were 2,418.3 and 6,361.4 nmol/L, respectively, in KBM5-ST1571(R1.0), and 97.2 and 2,497.3 nmol/L, respectively, in KBM7-ST1571R(1.0) cells. AMN107 inhibited autophosphorylation of Bcr-Abl kinase more effectively than imatinib in all cell lines. They had similar effects on cell cycle progression and apoptotic response in these cell lines. Among severe combined immunodeficient mice bearing KBM5 cells, mean survival times of groups treated with 10, 20, and 30 mg/kg/d of AMN107, starting day 20 after leukemic cell grafting and continuing for 20 days, were 144%, 159%, and 182%, respectively, compared with controls. These results strongly support investigation of the clinical efficacy of AMN107 in patients with CML. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. Novartis Inst Biomed Res, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Beran, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM mberan@mdanderson.org NR 39 TC 148 Z9 162 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 JUL 1 PY 2005 VL 11 IS 13 BP 4941 EP 4947 DI 10.1158/1078-0432.CCR-04-2601 PG 7 WC Oncology SC Oncology GA 944BQ UT WOS:000230400300041 PM 16000593 ER PT J AU Lynch, TJ Bogart, JA Curran, WJ DeCamp, MM Gandara, DR Goss, G Henschke, CI Jett Jr Johnson, BE Kelly, KL Le Chevalier, T Mulshine, JL Scagliotti, GV Schiller, JH Shaw, A Thatcher, N Vokes, EE Wood, DE Hart, C AF Lynch, TJ Bogart, JA Curran, WJ DeCamp, MM Gandara, DR Goss, G Henschke, CI Jett, JR Johnson, BE Kelly, KL Le Chevalier, T Mulshine, JL Scagliotti, GV Schiller, JH Shaw, A Thatcher, N Vokes, EE Wood, DE Hart, C TI Early stage lung cancer - New approaches to evaluation and treatment: Conference summary statement SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Thorac Surg Sect, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Radiat Oncol, Syracuse, NY USA. Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA USA. Ottawa Reg Canc Ctr, Ctr Canc Therapeut, Ottawa, ON K1Y 4K7, Canada. Cornell Univ, Weill Med Coll, Dept Radiol, New York, NY USA. Mayo Clin Rochester, Thorac Dis & Med Oncol, Rochester, MN USA. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80262 USA. Inst Gustave Roussy, Dept Med, Villejuif, France. NCI, Canc Res Ctr, Cell & Biol Branch, Expt Intervent Sect, Bethesda, MD 20892 USA. Univ Turin, Dept Clin & Biol Sci, S Luigi Gonzaga Hosp, Turin, Italy. Univ Wisconsin, Sch Med, Madison, WI USA. Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Washington, Div Cardiothorac Surg, Seattle, WA USA. InforMed, Narberth, PA USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 210, Boston, MA 02114 USA. EM tlynch@partners.org NR 0 TC 5 Z9 5 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 JUL 1 PY 2005 VL 11 IS 13 SU S BP 4981S EP 4983S DI 10.1158/1078-0432.CCR-05-9015 PG 3 WC Oncology SC Oncology GA 945JB UT WOS:000230497700001 PM 16000599 ER PT J AU Shaw, AT Kirsch, DG Jacks, T AF Shaw, AT Kirsch, DG Jacks, T TI Future of early detection of lung cancer: The role of mouse models SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Early Stage Lung Cancer CY OCT 01-02, 2004 CL Cambridge, MA ID COMPUTED-TOMOGRAPHY; OVARIAN-CANCER; MICE; IDENTIFICATION; BIOMARKER; SERUM; RAS AB Early detection represents one of the most promising approaches to improving lung cancer survival. To date, no screening strategies have been shown to decrease mortality from the disease. Furthermore, no reliable circulating biomarkers of lung cancer have been identified that allow early diagnosis. With the advent of gene targeting technology, new genetically engineered mouse models of lung cancer closely recapitulate the pathobiology of human disease. These mouse models have enabled novel approaches to early detection, including the identification of cancer-associated serum markers using proteomic technologies and the development of new molecular imaging tools. The application of innovative technologies to accurate mouse models promises to accelerate the discovery of new molecular targets and imaging biomarkers for the early detection of lung cancer. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Shaw, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners Canc Care, 100 Blossom St,Cox 809, Boston, MA 02114 USA. EM ashaw1@partners.org NR 29 TC 12 Z9 13 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 JUL 1 PY 2005 VL 11 IS 13 SU S BP 4999S EP 5003S DI 10.1158/1078-0432.CCR-05-9005 PG 5 WC Oncology SC Oncology GA 945JB UT WOS:000230497700005 PM 16000603 ER PT J AU Johnson, BE Rabin, MS AF Johnson, BE Rabin, MS TI Patient subsets benefiting from adjuvant therapy following surgical resection of non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Early Stage Lung Cancer CY OCT 01-02, 2004 CL Cambridge, MA ID RANDOMIZED-TRIAL; STAGE-II; CHEMOTHERAPY AB Adjuvant chemotherapy is the standard of therapy for some patients with stages I, II, and III breast and colon cancer. The therapeutic efficacy of adjuvant chemotherapy following surgical resection of early stage non-small cell lung cancer (NSCLC) has been less clear. A meta-analysis was reported in 1995 of patients who underwent surgical resection for early stage NSCILC and were then randomized to either observation or chemotherapy. This meta-analysis showed a 13% reduction in the hazard ratio of death, leading to a 5% absolute improvement in survival 5 years after the start of adjuvant cisplatin-based chemotherapy treatment compared with observation only. Multiple prospective randomized trials for patients with NSCLC were planned and undertaken to attempt to validate the observations of the meta-analysis. Six trials with >= 150 patients with early stage NSCLC (stages I-IIIA) on each arm have been reported in the last 2 years. Four of the six trials show a survival advantage for the patients with early stage NSCLC treated with adjuvant chemotherapy compared with those who underwent observation. The survival benefit in these four studies varies from a 4% to a 16% survival advantage at 4 to 5 years after the start of chemotherapy. The hazard ratio of death for the patients treated with chemotherapy ranged from 0.61 to 0.86 compared with patients on observation. Thus, the information available at the current time supports the administration of chemotherapy for patients with stages 113 and 11 NSCLC. Further research will be needed to define the role of adjuvant chemotherapy and its use in conjunction with chest radiotherapy for the treatment of patients with resected stages IA and IIIA NSCLC. C1 Dana Farber Canc Inst, Dept Med Oncol, Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org NR 8 TC 10 Z9 11 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 JUL 1 PY 2005 VL 11 IS 13 SU S BP 5022S EP 5026S DI 10.1158/1078-0432.CCR-05-9001 PG 5 WC Oncology SC Oncology GA 945JB UT WOS:000230497700009 PM 16000607 ER PT J AU Marty, FM Lowry, CM Rodriguez, M Milner, DA Pieciak, WS Sinha, A Fleckenstein, L Baden, LR AF Marty, FM Lowry, CM Rodriguez, M Milner, DA Pieciak, WS Sinha, A Fleckenstein, L Baden, LR TI Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID STERCORALIS; HYPERINFECTION; PLASMA AB There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Iowa, Coll Pharm, Div Clin & Adm Pharm, Iowa City, IA 52242 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org NR 19 TC 37 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2005 VL 41 IS 1 BP E5 EP E8 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932BY UT WOS:000229530400033 PM 15937753 ER PT J AU Chung, RT AF Chung, RT TI Acute hepatitis C virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PERSISTENCE AB Acute infection with hepatitis C virus (HCV) is a frequent but underrecognized problem among substance users, because it produces few symptoms. Despite this fact, a good deal has been learned recently from studies of cohorts of persons with acute HCV infection. Intensive study of these cohorts has suggested that there is a higher frequency of spontaneous clearance among persons with symptomatic infection and persons with vigorous adaptive immune responses. Similarly, polymorphisms for genes involved in innate immunity also appear to influence the outcome of acute HCV infection. Data on injection drug users with repeated exposures to HCV reveal the presence of partially protective immunity, which suggests that vaccine-based approaches may be feasible. Finally, antiviral therapy with interferon-based regimens for acute HCV infection produces significantly higher sustained virological responses than observed for chronic infection. Further work is needed to develop more-accurate assays for acute HCV infection, to define host and viral factors that predict outcome and to define the optimal duration and regimen of therapy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Liver Transplant Program, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [DK-57857] NR 15 TC 22 Z9 25 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2005 VL 41 SU 1 BP S14 EP S17 DI 10.1086/429490 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932CB UT WOS:000229530700003 PM 16265608 ER PT J AU Hilsabeck, RC Castellon, SA Hinkin, CH AF Hilsabeck, RC Castellon, SA Hinkin, CH TI Neuropsychological aspects of coinfection with HIV and hepatitis C virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-ALPHA; NEUROPSYCHIATRIC SYMPTOMS; TEST-PERFORMANCE; DRUG-USERS; INFECTION; IMPAIRMENT; DISORDERS; BRAIN; AIDS AB Infection with hepatitis C virus (HCV) is commonly seen in persons with human immunodeficiency virus (HIV) infection, because the viruses share risk factors for transmission; coinfection is a leading cause of morbidity and mortality among HIV-infected persons. Neuropsychological consequences of HIV infection are well established, and studies of HCV-infected persons have revealed neuropsychiatric dysfunction in this population as well. Investigators now are focusing on neuropsychological sequelae of coinfection with HIV and HCV, and preliminary results suggest that coinfection has a possible deleterious effect on global cognitive functioning consistent with frontal-subcortical dysfunction. Data on neuropsychiatric symptoms in coinfected persons are inconclusive at this time and are complicated by important differences in study populations (e. g., injection drug use and disease severity). This review summarizes what is known about neuropsychological aspects of monoinfection with HIV and HCV, as well as coinfection, discusses implications of these findings, and suggests future directions for this research area. C1 S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Robin.Hilsabeck@med.va.gov FU NIDA NIH HHS [R01 DA013799-01A1, R01 DA013799, DA-13799]; NIMH NIH HHS [R01 MH058552-02, T32 MH019535, R01 MH058552, MH-58552] NR 48 TC 34 Z9 35 U1 0 U2 2 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 JUL 1 PY 2005 VL 41 SU 1 BP S38 EP S44 DI 10.1086/429494 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932CB UT WOS:000229530700007 PM 16265612 ER PT J AU Mao, JT Cui, XY Reckamp, K Liu, M Krysan, K Dalwadi, H Sharma, S Hazra, S Strieter, R Gardner, B Dubinett, SM AF Mao, Jenny T. Cui, Xiaoyan Reckamp, Karen Liu, Ming Krysan, Kostyantyn Dalwadi, Harnisha Sharma, Sherven Hazra, Saswati Strieter, Robert Gardner, Brian Dubinett, Steven M. TI Chemoprevention strategies with cyclooxygenase-2 inhibitors for lung cancer SO CLINICAL LUNG CANCER LA English DT Review DE angiogenesis; arachidonic acid cascade; celecoxib; fluorescence bronchoscopy; invasion; prostaglandin E-2 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOTHELIAL GROWTH-FACTOR; DENDRITIC CELL-DIFFERENTIATION; LAMININ-5 GAMMA-2 CHAIN; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; PROSTAGLANDIN E-2; COLORECTAL-CANCER; PROSTATE-CANCER; FACTOR RECEPTOR AB Clinical lung cancer is the ultimate event resulting from a series of genetic and epigenetic alterations in the respiratory epithelium at risk. According to the "field carcinogenesis" theory, these alterations can occur throughout the entire lung. In individuals with a genetic predisposition combined with a sufficient amount of procarcinogenic environmental influences, a few of these sites may eventually progress to malignancies. Recent advances in the understanding of tumor biology have identified new therapeutic targets for lung cancer chemoprevention, among which is cyclooxgygenase (COX)-2. Ample preclinical data suggest that the COX-2/prostaglandin E-2 (PGE(2)) Signaling pathway plays a pivotal role in conferring the malignant phenotype. Produced primarily by the action of COX on the free arachidonic acid liberated from membrane phospholipids, overproduction of PGE(2), which is predominantly generated by upregulation of COX-2, is associated with a variety of mechanisms known to facilitate tumorigenesis. These mechanisms include abnormal expression of epithelial growth factors, epithelial and microvascular proliferation, resistance to apoptosis, and suppression of antitumor immunity. The lung is one of the major sites of PGE(2) production, and previous studies have shown elevated PGE(2) levels in bronchoalveolar lavage fluid of patients with bronchogenic carcinoma. In animal models, inhibition of COX-2 and PGE(2) synthesis suppresses lung tumorigenesis. These preclinical data suggesting the antineoplastic effect of COX-2 inhibitors provide the basis for several ongoing pilot clinical trials to determine the feasibility of COX-2 inhibition in chemoprevention of bronchogenic carcinoma. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med,Lung Canc Chemoprevent P, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Mao, JT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med,Lung Canc Chemoprevent P, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jmao@mednet.ucla.edu OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [K23 CA 88068, P50 CA 90388, U01 CA 96134-01] NR 141 TC 34 Z9 35 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JUL PY 2005 VL 7 IS 1 BP 30 EP 39 DI 10.3816/CLC.2005.n.019 PG 10 WC Oncology SC Oncology GA 113LZ UT WOS:000242600700005 PM 16098242 ER PT J AU Janne, PA Wozniak, AJ Belani, CP Keohan, ML Ross, HJ Polikoff, JA Mintzer, DM Taylor, L Ashland, J Ye, ZS Monberg, MJ Obasaju, CK AF Jaenne, Pasi A. Wozniak, Antoinette J. Belani, Chandra P. Keohan, Mary-Louise Ross, Helen J. Polikoff, Jonathan A. Mintzer, David M. Taylor, Loretta Ashland, Joseph Ye, Zhishen Monberg, Matthew J. Obasaju, Coleman K. TI Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: Outcomes of an expanded access program SO CLINICAL LUNG CANCER LA English DT Article DE chemotherapy-naive disease; compassionate-use program; efficacy; toxicity ID MULTITARGETED ANTIFOLATE; PHASE-III; CANCER; LY231514; MTA AB BACKGROUND: To date, few large studies have been reported of patients with peritoneal mesothelioma, and treatment of this disease has been largely extrapolated from the treatment of pleural disease. Hence, it was considered important to study and report on this specific patient population. Before the regulatory approval of pemetrexed, an expanded access program (EAP) provided access to eligible patients with malignant pleural or peritoneal mesothelioma. PATIENTS AND METHODS: Patients received pemetrexed 500 mg/m(2) alone or in combination with cisplatin 75 mg/m(2) once every 21 days for >= 6 cycles. All patients received folic acid, vitamin B-12, and steroid prophylaxis. Serious adverse events (SAEs) were compiled in a pharmacovigilance database, which included all patients in the EAP with pleural or peritoneal mesothelioma. From June 12, 2002 to February 18, 2004, 1056 patients with malignant mesothelioma were enrolled and received >= 1 dose of treatment at 462 sites in the United States. Of these patients, 98 (9.3%) had peritoneal mesothelioma (57 previously treated, 38 chemotherapy-naive, and 3 with missing data). RESULTS: Response data were available for 73 patients (43 previously treated, 28 chemotherapy-naive, and 2 not classified), indicating response rates of 23.3% for previously treated patients (0 complete responses [CRs], 10 partial responses [PRs], 21 cases of stable disease [SDs], 12 cases of progressive disease [PDs]) and 25% for chemotherapy-naive patients (3 CRs, 4 PRs, 12 SDs, and 9 PDs). Median survival was 13.1 months for previously treated patients and has not been reached for chemotherapy-naive patients. The most commonly reported SAEs for the total EAP were dehydration (7.2%), nausea (5.2%), and vomiting (4.9%). CONCLUSION: Pemetrexed with or without cisplatin had a favorable safety profile, and the disease control rate (CR + PR + SD) of 71.2% in the subset of patients with peritoneal mesothelioma indicated activity in this patient population. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Wayne State Univ, Karmanos Canc Inst, Dept Internal Med, Detroit, MI USA. Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Pittsburgh, PA 15260 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. Kaiser Hosp, Dept Hematol Oncol, San Diego, CA USA. Penn Hosp, Hematol Oncol Sect, Philadelphia, PA 19107 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St,Dana 1234, Boston, MA 02115 USA. NR 16 TC 63 Z9 69 U1 2 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JUL PY 2005 VL 7 IS 1 BP 40 EP 46 DI 10.3816/CLC.2005.n.020 PG 7 WC Oncology SC Oncology GA 113LZ UT WOS:000242600700006 PM 16098243 ER PT J AU Farabaugh, A Fava, M Mischoulon, D Sklarsky, K Petersen, T Alpert, J AF Farabaugh, A Fava, M Mischoulon, D Sklarsky, K Petersen, T Alpert, J TI Relationships between major depressive disorder and comorbid anxiety and personality disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PANIC DISORDER; TEMPERAMENT; DIMENSIONS; FEATURES AB Objective: The aim of the study was to examine whether comorbid anxiety disorders influence depressed patients' likelihood of meeting criteria for a personality disorder (PD) and whether comorbid anxiety disorders influence the stability of the PDs in patients with remitted depression. Methods: The initial sample consisted of 373 outpatients who met criteria for major depressive disorder (MDD) (by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition - Patient Edition) and who were enrolled in the 8-week acute treatment phase of a study of fluoxetine for MDD. Sixty-four subjects who responded to fluoxetine treatment in the acute phase met criteria for remission throughout a 26-week continuation phase during which they remained on fluoxetine with or without cognitive behavioral therapy. Stability of PDs was defined as meeting criteria for a PD at both beginning and end point of the continuation treatment phase. Results: Before fluoxetine treatment, anxious depressed patients (defined as meeting criteria for MDD as well as at least one comorbid anxiety disorder) were significantly more likely to meet criteria for any comorbid PD diagnosis compared with depressed patients without comorbid anxiety disorders. In particular, there was a significant relationship between the presence of Cluster A and C PDs and the presence of anxious depression at baseline before antidepressant treatment. After successful treatment of MDD, we found a significant relationship between anxious depression diagnosed at baseline and the stability of a Cluster C PD diagnosis. Conclusion: Anxious depression may place patients at greater risk of having a PD diagnosis, especially one from Cluster A or C. Once the depression remits, patients who initially met criteria for anxious depression may be more likely to maintain a Cluster C PD diagnosis compared with patients initially diagnosed with MDD alone. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Farabaugh, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. EM afarabaugh@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [5R01MH56057-02] NR 28 TC 16 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2005 VL 46 IS 4 BP 266 EP 271 DI 10.1016/j.comppsych.2004.10.005 PG 6 WC Psychiatry SC Psychiatry GA 942QB UT WOS:000230295800005 PM 16175757 ER PT J AU Caramez, MP Borges, JB Tucci, MR Okamoto, VN Carvalho, CRR Kacmarek, RM Malhotra, A Velasco, IT Amato, MBP AF Caramez, MP Borges, JB Tucci, MR Okamoto, VN Carvalho, CRR Kacmarek, RM Malhotra, A Velasco, IT Amato, MBP TI Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE intrinsic positive end-expiratory pressure; applied positive end-expiratory pressure; mechanical ventilation; obstructive pulmonary disease; waterfall effect; negative effort dependence ID CONTROLLED MECHANICAL VENTILATION; FLOW LIMITATION; PULMONARY-DISEASE; SEVERE ASTHMA; DYNAMIC HYPERINFLATION; COPD PATIENTS; PEEP; FAILURE; VALIDATION; COLLAPSE AB Objective: To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical veDesign: External-PEEP was applied stepwise (2 cm H2O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (V-T: 6 and 9 mL/kg), were tested.ntilation. The controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized. Setting: A hospital intensive care unit. Patients: Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, > 20 cm H2O/L per sec) and the presence of intrinsic-PEEP (>= 5 cm H2O) despite the use of very low minute ventilation. Interventions: All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography. Measurements and Main Results. Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern. Conclusions. External-PEEP application may relieve overinflation in selected patients with airway obstruction during controlled mechanical ventilation. No a priori information about disease, mechanics, or ventilatory settings was predictive of the response. An empirical PEEP trial investigating plateau pressure response in these patients appears to be a reasonable strategy with minimal side effects. C1 Univ Sao Paulo, Sch Med, Emergency Dept, Resp & Emergency Intens Care Unit, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Div Pulm, Resp Intens Care Unit, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Hosp Clin, BR-05508 Sao Paulo, Brazil. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Caramez, MP (reprint author), Univ Sao Paulo, Sch Med, Emergency Dept, Resp & Emergency Intens Care Unit, BR-05508 Sao Paulo, Brazil. RI Carvalho, Carlos/H-2161-2011 FU NHLBI NIH HHS [R01 HL073146-02, R01 HL073146]; NIA NIH HHS [K23 AG024837-02, K23 AG024837] NR 44 TC 45 Z9 56 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2005 VL 33 IS 7 BP 1519 EP 1528 DI 10.1097/01.CCM.0000168044.98844.30 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 947GB UT WOS:000230630300007 PM 16003057 ER PT J AU Badjatia, N Topcuoglu, MA Buonanno, FS Smith, EE Nogueira, RG Rordorf, GA Carter, BS Ogilvy, CS Singhal, AB AF Badjatia, N Topcuoglu, MA Buonanno, FS Smith, EE Nogueira, RG Rordorf, GA Carter, BS Ogilvy, CS Singhal, AB TI Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage SO CRITICAL CARE MEDICINE LA English DT Article DE symptomatic vasospasm; aneurysmal subarachnoid hemorrhage; blood glucose level; hyperglycemia ID INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; POOR-GRADE PATIENTS; CEREBRAL VASOSPASM; TRANSCRANIAL DOPPLER; DIABETES-MELLITUS; INFARCT SIZE; POSTSTROKE HYPERGLYCEMIA; PLASMA-GLUCOSE; BLOOD-GLUCOSE AB Objective: To determine the relationship between blood glucose levels (mg/dL) and occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal subarachnoid hemorrhage. Design: Retrospective observational study of 352 patients with subarachnoid hemorrhage admitted within 48 hirs of ictus between January 1995 and June 2002. Setting: Neurointensive care unit. Patients: Adult patients admitted after subarachnoid hemorrhage. Interventions: None. Measurements and Main Results. Variables included age; Hunt-Hess classification score; Fisher group; insulin use; infectious disease status; history of diabetes mellitus; and blood glucose values. Poor clinical outcome was defined by a modified Rankin score >= 3, and hyperglycemia was defined by a blood glucose level > 140 mg/dL. Mean daily blood glucose values were assessed from admission to development of VSP or day 14. Mean admission blood glucose value, mean inpatient blood glucose value, insulin use, infectious disease status, Hunt-Hess classification score, Fisher group, and history of diabetes mellitus were entered in a Cox proportional hazards model. VSP occurred in 103 (29.2%) of 352 patients. Mean admission blood glucose values (176.6 +/- 40.3 mg/dL vs. 162.3 +/- 47.8 mg/dL; p = .01) and mean inpatient blood glucose values (166.2 +/- 24.7 mg/dL vs. 155.8 +/- 29.7 mg/dL; p = .001) were significantly higher in patients with VSP. Mean inpatient blood glucose value (relative risk, 1.01; 95% confidence interval, 1.0-1.03; p = .04), Hunt-Hess classification score >= 3 (relative risk, 2.23; 95% confidence interval, 1.21-3.99; p = .02), and Fisher group score of 3 (relative risk, 1.28; 95% confidence interval, 1.15-3.1; p = .05) increased the risk for VSP. Hyperglycemia was associated with longer length of stay in the neurointensive care unit (14.5 +/- 7.1 days vs. 11.6 +/- 5.4 days; p < .001) and poor outcome at discharge (modified Rankin score >= 3: 58.9% vs. 18.8%; p < .001). Conclusions. Mean inpatient blood glucose value is associated with the development of VSP and may represent a target for therapy to prevent VSP and improve clinical outcomes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. Akdeniz Univ Hosp Neurosonol Res Lab, Antalya, Turkey. Massachusetts Gen Hosp, Neurosci Intens Care Unit, Boston, MA 02115 USA. RP Badjatia, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. OI Smith, Eric/0000-0003-3956-1668 NR 57 TC 72 Z9 74 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2005 VL 33 IS 7 BP 1603 EP 1609 DI 10.1097/01.CCM.0000168054.60538.2B PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 947GB UT WOS:000230630300019 PM 16003069 ER PT J AU Dai, YM Ma, E Tang, E Zhang, J Li, ZJ Huang, XD Yao, YG AF Dai, YM Ma, E Tang, E Zhang, J Li, ZJ Huang, XD Yao, YG TI Paratactic assembly of two distinct units into a unique 3D architecture SO CRYSTAL GROWTH & DESIGN LA English DT Article ID COORDINATION POLYMERS; HYDROGEN-BOND; CRYSTAL; TRANSITION; COMPLEXES; NETWORKS; LIGANDS; CHAIN AB The hydrothermal reaction of zinc acetate with isophthalate (ip) and 4,4-bipyridine (4,4-bipy) in alkaline solution yielded a novel coordination polymer [Zn(ip)(4,4-bipy)(2)] [Zn(ip)(4,4-bipy)] center dot 0.25H(2)O, whose three-dimensional network was constructed by the paratactic assembly of two distinct units in an ABCD array. C1 Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350002, Fujian, Peoples R China. Fujian Normal Univ, Coll Chem & Mat Sci, Fuzhou 350007, Peoples R China. Fuzhou Univ, Coll Chem & Chem Engn, Fuzhou 350002, Peoples R China. Massachusetts Gen Hosp, Massachusetts Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Yao, YG (reprint author), Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350002, Fujian, Peoples R China. EM yyg@fjirsm.ac.cn RI Zhang, Jian/B-5056-2011 OI Zhang, Jian/0000-0003-3373-9621 NR 21 TC 61 Z9 65 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1528-7483 J9 CRYST GROWTH DES JI Cryst. Growth Des. PD JUL-AUG PY 2005 VL 5 IS 4 BP 1313 EP 1315 DI 10.1021/cg0500425 PG 3 WC Chemistry, Multidisciplinary; Crystallography; Materials Science, Multidisciplinary SC Chemistry; Crystallography; Materials Science GA 944HY UT WOS:000230419200002 ER PT J AU Dean, BB Dylan, M Gano, A Knight, K Ofman, JJ Levine, BS AF Dean, BB Dylan, M Gano, A Knight, K Ofman, JJ Levine, BS TI Erythropoiesis-stimulating protein therapy and the decline of renal function: a retrospective analysis of patients with chronic kidney disease SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE chronic kidney disease; disease progression; erythropoiesis-stimulating protein; renal function ID INTRAVENOUS IRON; SERUM CREATININE; HEART-FAILURE; UNITED-STATES; PROGRESSION; ANEMIA; CARE; INSUFFICIENCY; NEPHROPATHY; PREVALENCE AB Background/Aims: Previous studies have hinted at possible associations between anemia and progression of renal disease. The study objective was to determine whether treatment with erythropoiesis-stimulating proteins (ESPs) can curb the rate of decline in renal function in pre-dialysis patients with chronic kidney disease (CKD). Methods: Observational, before/after analysis using electronic medical records from the Veterans Administration (VA). Included patients had at least two measurements of serum creatinine levels before and after ESP treatment initiation. The Cockcroft-Gault formula was used to derive estimates of glomerular filtration rate (GFR). Rate of renal function decline prior to and following initiation of therapy were compared. Results: One hundred and twenty two patients with renal impairment levels of Stage 3 (moderate) or Stage 4 (severe) at ESP treatment initiation were identified. Over 80% of patients initiated therapy with either Grade 1 or Grade 2 anemia. The rate of renal function decline was calculated as the slope of the least-squares linear regression line of the inverse serum creatinine over time during the pre-treatment initiation and post-treatment initiation time periods. Overall, patients experienced a slowing in the rate of renal function decline after treatment was initiated (mean pretreatment initiation rate of -0.094 dL/mg/yr versus mean post-treatment initiation rate of -0.057 dL/mg/yr). Conclusion: Renal function declined at a slower rate following ESP initiation. Results are consistent with prior studies indicating delayed dialysis initiation in patients treated with ESPs. Analyses were limited by the observational study design and lack of information regarding some potential confounders. Longer-term, prospective trials are needed to determine whether ESPs slow progression of renal disease and the potential magnitude of such an effect. C1 Cerner Hlth Insights, Beverly Hills, CA 90212 USA. Cedars Sinai Dept Med, Los Angeles, CA USA. Cedars Sinai Dept Hlth Serv Res, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Gano, A (reprint author), Cerner Hlth Insights, 9100 wilshire Blvd,Suite 655,E Tower, Beverly Hills, CA 90212 USA. EM agano@cerner.com NR 23 TC 30 Z9 33 U1 0 U2 0 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, 26-32 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUL PY 2005 VL 21 IS 7 BP 981 EP 987 DI 10.1185/030079905X49644 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 946HF UT WOS:000230562300001 PM 16004664 ER PT J AU Mueller, T Podolsky, DK AF Mueller, T Podolsky, DK TI Nucleotide-binding-oligomerization domain proteins and toll-like receptors: sensors of the inflammatory bowel diseases' microbial environment SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE immune tolerance; inflammatory bowel disease; intestinal epithelial cell monolayer; intestinal microflora; intestinal mucosa; nuclear factor-kappa B; nucleotide-binding-oligomerization domain protein; toll-like receptor ID INTESTINAL EPITHELIAL-CELLS; REGULATORY T-CELLS; NF-KAPPA-B; ADAPTIVE IMMUNE-RESPONSES; CROHNS-DISEASE; MURAMYL DIPEPTIDE; BACTERIAL PEPTIDOGLYCAN; NOD2/CARD15 GENOTYPE; DIAMINOPIMELIC ACID; ULCERATIVE-COLITIS AB Purpose of review Chronic inflammatory bowel diseases appear to result from inappropriate immune responses driven by apparently normal intestinal microflora in genetically susceptible hosts. This review focuses on recently described mechanisms balancing toll-like receptor and nucleotide-binding-oligomerization domain activation in the face of ubiquitous enteric flora. Recent findings Toll-like receptor and nucleotide-binding-oligomerization domain signaling plays an integral role in the close collaboration between the intestinal epithelial cell monolayer and adjacent mucosal immune cells. Pathways activated by functional cytosolic nucleotide-binding-oligomerization domain proteins appear to interact with those mediated by membrane-associated toll-like receptors in the innate and adaptive immune defense against intra- and extracellular pathogens. Nucleotide-binding-oligomerization domain-mediated signaling may also control toll-like receptor-induced proinflammatory pathways. Summary Intersections between toll-like receptor and nucleotide-binding-oligomerization domain pathways may exist to refine the host immune response to pathogens and prevent undesired immune stimulation driven by the intestinal microbiota. Deficient toll-like receptor and nucleotide-binding-oligomerization domain function due to genetic variability is associated with an increased susceptibility to the development of inflammatory bowel disease. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org NR 78 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 2005 VL 21 IS 4 BP 419 EP 425 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 947QN UT WOS:000230661300005 PM 15930981 ER PT J AU Keith, RL Miller, YE AF Keith, RL Miller, YE TI Lung cancer: genetics of risk and advances in chemoprevention SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE chemoprevention; genetic susceptibility; lung cancer; prostacyclin; retinoids ID SQUAMOUS-CELL CARCINOMA; AIR-FLOW OBSTRUCTION; 2ND PRIMARY TUMORS; PHASE IIB TRIAL; BETA-CAROTENE; VITAMIN-A; BRONCHIAL EPITHELIUM; RANDOMIZED-TRIAL; DIETARY MYOINOSITOL; NECK-CANCER AB Purpose of review The current article reviews recent advances in genetic susceptibility and chemoprevention of lung cancer. Recent findings Linkage analysis has identified a locus on chromosome 6q23-25 that determines susceptibility to lung cancer in families with multiple members with cancer of the lung, throat, and larynx. Obligate gene carriers are sensitive to even small tobacco smoke exposure in terms of increased lung cancer risk. Variation in other genes, particularly those regulating the activation or inactivation of carcinogens, has been implicated in determining lung cancer risk. Epidemiologic and preclinical studies suggest that chemoprevention of lung cancer is an achievable goal. Early trials with beta-carotene supplementation, however, have revealed a harmful effect. Promising new agents must be evaluated in both preclinical models and in intermediate end point biomarker trials before being taken to large primary prevention trials, and lung cancer chemoprevention should only be attempted within controlled clinical trials. Summary We are poised to learn a great deal about the genetic susceptibility to lung cancer, which will not only allow definition of groups with extremely high risk, but may also yield new insights into processes that determine innate susceptibility or resistance to lung carcinogenesis, Chemoprevention of lung cancer is not yet ready for clinical application. As a result of the large number of lung cancer deaths and the large number of at-risk individuals, even modestly effective chemoprevention could save many lives. C1 Univ Colorado, Denver Vet Affairs Med Ctr, Ctr Canc,Pulm Sect, Pulm Sci & Crit Care Med Div,Tobacco Related Mali, Denver, CO 80220 USA. RP Miller, YE (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Ctr Canc,Pulm Sect, Pulm Sci & Crit Care Med Div,Tobacco Related Mali, 1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu FU NCI NIH HHS [P30 CA46934, P50 CA58187] NR 70 TC 20 Z9 20 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD JUL PY 2005 VL 11 IS 4 BP 265 EP 271 DI 10.1097/01.mcp.0000166493.77412.2d PG 7 WC Respiratory System SC Respiratory System GA 938QC UT WOS:000230016900001 PM 15928489 ER PT J AU Kelliher, AS Parent, DW Anderson, DC Dorn, ME Hahn, JL Eapen, S Preffer, FI AF Kelliher, AS Parent, DW Anderson, DC Dorn, ME Hahn, JL Eapen, S Preffer, FI TI Novel use of the BD FACS (TM) SPA to automate custom monoclonal antibody panel preparations for immunophenotyping SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE flow cytometry; immunophenotyping; robotics; staining techniques; SPA; automation ID FLOW-CYTOMETRY; HEMATOLOGIC MALIGNANCY AB Background: The effective and accurate diagnosis of hematologic malignancies relies on flow cytometric immunophenotyping. Selected combinations of monoclonal antibodies (mAbs) arranged in multicolor panels allow for the accurate definition of normal and abnormal hematologic cell populations. The most time-consuming and crucial step in the staining process involves dispensing combinations of multiple mAbs into their appropriate staining tubes. This step is prone to error, requires concentration and accuracy, and is dependent on technologist experience. The Becton Dickinson BioScience (BD) FACS (TM) Sample Prep Assistant (SPA) is touted as a breakthrough in automated in vitro diagnostic sample preparation. The SPA is designed to automate BD MultiTEST (TM) and BD TriTest lyse/no-wash assays. However, because most cases in our laboratory require tedious application of unique four-color mAb cocktails for leukemia and lymphoma testing, we wondered whether the SPA would be helpful in accurately dispensing these mixtures. Methods: The mAb panels were prepared by the SPA in two separate timed runs and an separate days. Eleven specimens (nine from patients and two from normal volunteers) were split and stained with four-color cocktails created by the SPA or manually. The percentage of positive (%P) cells and mean fluorescent intensity for each mAb pair were determined. These values were plotted against each other and correlation values were calculated. To quantitate timesaving in the laboratory, two technologists prepared individually the same mAb panels and were timed. Results: The correlation between the two methods was high; r(2) was 0.988 for 158 %P antigen pairs; no bias between the manual and robotic methods was detected with the Wilcoxon rank test. Bland-Altman analysis indicated no obvious relation between the difference and the mean of %P cells, suggesting that the SPA successfully dispensed antibodies for leukemia/lymphoma panels. The two methods may be interchangeable, although the limited sample size prohibits this conclusion from Bland-Altman statistics alone. In addition, one possible error was detected in the SPA-prepared panels. The SPA averaged 65 min/run, the experienced technologist 12.95 min/run, and the inexperienced technologist 54.9 min/run. Conclusions: SPA dispensing time was twice the average manual dispensing time; however, SPA use was completely automated and freed the technologist to perform other tasks. SPA use permitted preemptive preparation of mAb panels and thus streamlined processing; however, the cost of the assay and the amount of reagent waste increased. It is certain that software modifications by BD could decrease the SPA reagent dispense time and decrease the cost associated with reagent waste when the SPA is used in this novel fashion. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA USA. RP Kelliher, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, BA Warren Bldg Room 112, Boston, MA 02114 USA. EM asallen@partners.org NR 8 TC 2 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2005 VL 66B IS 1 BP 40 EP 45 DI 10.1002/cyto.b.20055 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 937LA UT WOS:000229924400006 PM 15918157 ER PT J AU Kobayashi, T Kronenberg, HM Foley, J AF Kobayashi, T Kronenberg, HM Foley, J TI Reduced expression of the PTH/PTHrP receptor during development of the mammary gland influences the function of the nipple during lactation SO DEVELOPMENTAL DYNAMICS LA English DT Article DE nipple; PTHrP; PTH/PTHrP receptor; mammary gland development; smooth muscle ID HORMONE-RELATED PROTEIN; VASCULAR SMOOTH-MUSCLE; PARATHYROID-HORMONE; MATRIX METALLOPROTEINASE-2; REPRODUCTIVE-CYCLE; CONNECTIVE-TISSUE; RELAXIN; GROWTH; MICE; OVEREXPRESSION AB Signaling by the parathyroid hormone/parathyroid hormone-related protein receptor (Ppr) is necessary for mammary gland development beyond the early induction stage in mice. We used a series of murine models of reduced Ppr expression to determine how diminished receptor signaling influences mammary development. Reduction of Ppr expression to very low levels prevented mammary gland development. A less-severe reduction in Ppr expression permitted progression of mammary gland development beyond the induction stage, but the nipples of these mice were dramatically smaller than those of controls, with altered epidermis and connective tissue. Mothers with reduced expression of Ppr could not successfully nurse pups; however, the lactating glands did produce milk but could not efficiently deliver it. This finding was associated with reduced levels of matrix metalloproteinase-2 and an absence of pregnancy-associated remodeling of connective tissue matrix in the nipple. Reduced smooth muscle appears to underlie the majority of nipple deficiencies in mice with lower levels of the Ppr expression. (c) 2005 Wiley-Liss, Inc. C1 Indiana Univ, Sch Med, Dept Dermatol, Bloomington, IN 47405 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Foley, J (reprint author), Indiana Univ, Sch Med, Dept Dermatol, Jordan Hall, Bloomington, IN 47405 USA. EM jgfoley@indiana.edu FU NIAMS NIH HHS [AR45585, AR44855]; NIDDK NIH HHS [DK56246] NR 36 TC 16 Z9 16 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 2005 VL 233 IS 3 BP 794 EP 803 DI 10.1002/dvdy.20406 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 936YS UT WOS:000229892100009 PM 15880431 ER PT J AU Aiello, LP AF Aiello, LP CA PKC-DRS Study Grp TI The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy initial - Results of the protein kinase C beta inhibitor diabetic retinopathy study (PKC-DRS) multicenter randomized clinical trial SO DIABETES LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; BLOOD-RETINAL BARRIER; MACULAR EDEMA; SELECTIVE INHIBITOR; CELL GROWTH; ACTIVATION; LY333531; NEOVASCULARIZATION; COMPLICATIONS AB The purpose of this study was to evaluate the safety and efficacy of the orally administered protein kinase C (PKC) P isoform-selective inhibitor ruboxistaurin (RBX) in subjects with moderately severe to very severe nonproliferative diabetic retinopathy (NPDR). In this multicenter, double-masked, randomized, placebo-controlled study, 252 subjects received placebo or RBX (8, 16, or 32 mg/day) for 36-46 months. Patients had an Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy severity level between 47B and 53E inclusive, an ETDRS visual acuity of 20/125 or better, and no history of scatter (pan-retinal) photocoagulation. Efficacy measures included progression of DR, moderate visual loss (MVL) (doubling of the visual angle), and sustained MVL (SMVL). RBX was well tolerated without significant adverse effects but had no significant effect on the progression of DR Compared with placebo, 32 mg/day RBX was associated with a delayed occurrence of MVL (log rank, P = 0.038) and of SMVL (P = 0.226). RBX reduction of SMVL was evident only in eyes with definite diabetic macular edema at baseline (10% 32 mg/day RBX vs. 25% placebo, P = 0.017). In multivariable Cox proportional hazard analysis, 32 mg/ day RBX significantly reduced the risk of MVL compared with placebo (hazard ratio 0.37 [95% Cl 0.17-0.801, P = 0.012). In this clinical trial, RBX was well tolerated and reduced the risk of visual loss but did not prevent DR progression. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 46 TC 135 Z9 141 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2005 VL 54 IS 7 BP 2188 EP 2197 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SI UT WOS:000230164000034 ER PT J AU Hull, RL Shen, ZP Watts, MR Kodama, K Carr, DB Utzschneider, KM Zraika, S Wang, F Kahn, SE AF Hull, RL Shen, ZP Watts, MR Kodama, K Carr, DB Utzschneider, KM Zraika, S Wang, F Kahn, SE TI Long-term treatment with rosiglitazone and metformin reduces the extent of, but does not prevent, islet antyloid deposition in mice expressing the gene for human islet antyloid polypeptide SO DIABETES LA English DT Article ID BETA-CELL APOPTOSIS; TYPE-2 DIABETES-MELLITUS; AMYLOID FIBRIL FORMATION; FREE FATTY-ACID; IMPAIRED GLUCOSE-TOLERANCE; HUMAN PANCREATIC-ISLETS; INSULIN SENSITIVITY; TRANSGENIC MICE; MOUSE MODEL; PHARMACOLOGICAL-TREATMENT AB Islet amyloid deposition in type 2 diabetes is associated with reduced beta-cell mass. Therefore, interventions aimed at reducing islet amyloid formation may help preserve P-cell mass in type 2 diabetes. Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce P-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits. We hypothesized that this reduced P-cell secretory demand would lead to reduced islet amyloid formation. Human IAPP (MAPP) transgenic mice, a model of islet amyloid, were treated for 12 months with rosiglitazone (1.5 mg (.) kg(-1) (.) day(-1), n = 19), metformin (1 g (.) kg(-1) (.) day(-1), n = 18), or control (n = 17). At the end of the study, islet amyloid prevalence (percent islets containing amyloid) and severity (percent islet area occupied by amyloid), islet mass, P-cell mass, and insulin release were determined. Islet amyloid prevalence (44 8, 13 4, and 11 3% for control, metformin-, and rosiglitazone-treated mice, respectively) and severity (9.2 +/- 3.0, 0.22 +/- 0.11, and 0.10 +/- 0.05% for control, metformin-, and rosiglitazone-treated mice, respectively) were markedly reduced with both rosiglitazone (P < 0.001 for both measures) and metformin treatment (P < 0.001 for both measures). Both treatments were associated with reduced insulin release assessed as the acute insulin response to intravenous glucose (2,189 857, 621 256, and 14 158 pmol/l for control, metformin-, and rosiglitazone-treated mice, respectively; P < 0.05 for metformin vs. control and P < 0.005 for rosiglitazone vs. control), consistent with reduced secretory demand. Similarly, islet mass (33.4 +/- 7.0, 16.6 +/- 3.6, and 12.2 +/- 2.1 mg for control, metformin-, and rosiglitazone-treated mice, respectively) was not different with metformin treatment (P = 0.06 vs. control) but was significantly lower with rosiglitazone treatment (P < 0.05 vs. control). When the decreased islet mass was accounted for, the islet amyloid-related decrease in beta-cell mass (percent P-cell mass/islet mass) was ameliorated in both rosiglitazone and metformin-treated animals (57.9 +/- 3.1, 64.7 +/- 1.4, and 66.1 +/- 1.6% for control, metformin-, and rosiglitazone-treated mice, respectively; P < 0.05 for metformin or rosiglitazone vs. control). In summary, rosiglitazone and metformin protect beta-cells from the deleterious effects of islet amyloid, and this effect may contribute to the ability of these treatments to alleviate the progressive loss of beta-cell mass and function in type 2 diabetes. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98108 USA. RP Hull, RL (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Hull, Rebecca/0000-0001-9690-4087 FU NCRR NIH HHS [RR16066] NR 50 TC 49 Z9 54 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2005 VL 54 IS 7 BP 2235 EP 2244 DI 10.2337/diabetes.54.7.2235 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SI UT WOS:000230164000040 PM 15983227 ER PT J AU Russell, LB Valiyeva, E Roman, SH Pogach, LM Suh, DC Safford, MM AF Russell, LB Valiyeva, E Roman, SH Pogach, LM Suh, DC Safford, MM TI Hospitalizations, nursing home admissions, and deaths attributable to diabetes SO DIABETES CARE LA English DT Article ID MANAGED-CARE POPULATION; LIFE-STYLE; MEDICAL-CARE; COMPLICATIONS; MELLITUS; COSTS; INTERVENTION; MORTALITY; RISK; REDUCTION AB OBJECTIVE - To estimate all-cause hospitalizations, nursing home admissions, and deaths attributable to diabetes using a new methodology based on longitudinal data for a representative sample of older U.S. adults. RESEARCH DESIGN AND METHODS - A simulation model, based on data from the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Followup Study was used to represent the natural history of diabetes and control for a variety of baseline rise factors. The model was applied to 6,265 NHANES III adults aged 45-74 years. The prevalence of risk factors in NHANES III, fielded in 1988-1994, better represents today's adults. RESULTS - For all NHANES III adults aged 45-74 years, a diagnosis of diabetes accounted for 8.6% of hospitalizations, 12.3% of nursing home admissions, and 10.3% of deaths in 1988-1994. For people with diabetes, diabetes alone was responsible for 43.4% of hospitalizations, 52.1% of nursing home admissions, and 47% of deaths. Adjusting for related cardiovascular conditions, which may provide more accurate estimates of attributable risks for people with diabetes, increased these estimates to 51.4, 57.1, and 56.8%, respectively. CONCLUSIONS - Risks of institutionalization and death attributable to diabetes are large. Efforts to translate recent trials of primary prevention into practice and continued efforts to prevent complications of diabetes could have a substantial impact on hospitalizations, nursing home admissions, and deaths and their societal costs. C1 Rutgers State Univ, Inst Hlth, New Brunswick, NJ 08901 USA. Rutgers State Univ, Dept Econ, New Brunswick, NJ 08901 USA. Rutgers State Univ, Ernest Mario Sch Pharm, New Brunswick, NJ 08901 USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ 08854 USA. New Jersey Vet Adm Hlth Care Syst, E Orange, NJ USA. Univ Alabama, Deep S Ctr Effectivesness, Birmingham VA Med Ctr, Birmingham, AL USA. RP Russell, LB (reprint author), Rutgers State Univ, Inst Hlth, 30 Coll Ave, New Brunswick, NJ 08901 USA. EM lrussell@rci.rutgers.edu NR 26 TC 25 Z9 26 U1 0 U2 2 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 JUL PY 2005 VL 28 IS 7 BP 1611 EP 1617 DI 10.2337/diacare.28.7.1611 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800011 PM 15983309 ER PT J AU McMahon, GT Gomes, HE Hohne, SH Hu, TMJ Levine, BA Conlin, PR AF McMahon, GT Gomes, HE Hohne, SH Hu, TMJ Levine, BA Conlin, PR TI Web-based care management in patients with poorly controlled diabetes SO DIABETES CARE LA English DT Article ID RANDOMIZED-TRIAL; MEDICAL INFORMATION; IMPROVE OUTCOMES; GLYCEMIC CONTROL; SELF-MANAGEMENT; INTERNET; QUALITY; SYSTEM; EDUCATION; PROGRAM AB OBJECTIVE - To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS - For this study, 104 patients with diabetes and HbA(1c) (A1C) >= 9.0% who received their care at a Department of Veterans Affairs medical center were recruited. All participants completed a diabetes education class and were randomized to continue with their usual care (n = 52) or receive web-based care management (n = 52), The web-based group received a notebook computer, glucose and blood pressure monitoring devices, and access to a care management website. The website provided educational modules, accepted uploads from monitoring devices, and had an internal messaging system for patients to communicate with the care manager. RESULTS - Participants receiving web-based care management had to lower A1C over 12 months (P < 0.05) when compared with education and usual care. Persistent website users had greater improvement in A1C when compared with intermittent users (-1.9 vs. -1.2%; P = 0.051) or education and usual care (-1.4%; P < 0.05). A larger number of website data uploads was associated with a larger decline in A1C (highest tertile - 2.1% lowest tertile - 1.0%: P < 0.02). Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure (P < 0.01). HDL cholesterol rose and triglycerides fell in the web-based group (P < 0.05). CONCLUSIONS - Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes. C1 VA Boston Healthcare Syst, Med Serv, Boston, MA 02130 USA. Brigham & Womens Hosp, Div Endocrinol, Diabet & Hypertens Div, Boston, MA 02115 USA. Georgetown Univ, Med Ctr, Imaging Sci & Informat Syst Ctr, Washington, DC 20007 USA. RP Conlin, PR (reprint author), VA Boston Healthcare Syst, Med Serv, 150 S Huntington Ave, Boston, MA 02130 USA. EM paul.conlin@med.va.gov RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 FU NIDDK NIH HHS [K24 DK063214, K24-DK06321] NR 26 TC 138 Z9 140 U1 0 U2 9 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 JUL PY 2005 VL 28 IS 7 BP 1624 EP 1629 DI 10.2337/diacare.28.7.1624 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800013 PM 15983311 ER PT J AU Skyler, JS Weinstock, RS Raskin, P Yale, JF Barrett, E Gerich, JE Gerstein, HC AF Skyler, JS Weinstock, RS Raskin, P Yale, JF Barrett, E Gerich, JE Gerstein, HC CA Inhaled Insul Diabetes Study Grp TI Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects - A 16-month, randomized, comparative trial SO DIABETES CARE LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Diabetes-Association CY JUN 14-18, 2002 CL SAN FRANCISCO, CA SP Amer Diabet Assoc ID MICROVASCULAR COMPLICATIONS; GLYCEMIC CONTROL; MELLITUS; THERAPY; INJECTION; EFFICACY; EXUBERA; 6-MONTH; SAFETY AB OBJECTIVE - Despite the demonstrated benefits of glycemic control, patient acceptance of basal/bolus insulin therapy for type 1 diabetes has been slow. We Investigated whether basal/bolus insulin regimen involving rapid-acting, dry powder, inhaled insulin Could provide glycemic control comparable with a basal/bolus subcutaneous regimen. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (ages 12-65 years) received twice-daily subcutaneous NPH insulin and were randomized to premeal inhaled insulin (n = 163) or subcutaneous regular insulin (n = 165) for 6 months. RESULTS - Mean glucosylated hemoglobin (A1C) decreased comparably from baseline in the inhaled and subcutaneous insulin groups (-0.3 and -0.1%, respcctively adjusted difference -0.16% [CI -0.34 to 0.01]), with a similar percentage of subjects achieving A1C < 7%. Although 2-h postprandial glucose reductions were comparable between the groups, fasting plasma glucose levels declined more in the inhaled than in the subcutaneous insulin group (adjusted difference -39.5 mg/dl [CI -57.5 to -21.6]). Inhaled insulin was associated with a lower overall hypoglycemia rate but higher severe hypoglycemia rate. The overall hypoglycemia rate (episodes/patient-month) was 9.3 (inhaled) vs. 9.9 (subcutaneous) (risk ratio [RR] 0.94 [CI 0.91-0.97]), and the severe hypoglycemia rate (episodes/100 patient-months) was 6.5 vs 3.3 (RR 2.00 [CI 1.28-3.12]). Increased insulin antibody serum binding without associated clinical manifestations occurred in the inhaled insulin group. Pulmonary function between the groups was comparable, except for a decline in carbon monoxide-diffusing capacity in the inhaled insulin group without any clinical correlates. CONCLUSIONS - Inhaled insulin may provide an alternative for the management of type 1 diabetes as part of a basal/bolus strategy in patient, who are unwilling or unable to use preprandial insulin injections. C1 Univ Miami, Sch Med, Miami, FL 33136 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. Vet Affairs Med Ctr, Syracuse, NY USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Royal Victoria Hosp, McGill Nutr & Food Sci Ctr, Montreal, PQ H3A 1A1, Canada. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Univ Rochester, Sch Med, Rochester, NY USA. McMaster Univ, Div Endocrinol & Metab, Hamilton, ON L8S 4L8, Canada. RP Skyler, JS (reprint author), Univ Miami, Sch Med, 1450 NW 10th Ave,Suite 3054, Miami, FL 33136 USA. EM jskyler@miami.edu RI Skyler, Jay/F-4211-2016 NR 26 TC 123 Z9 130 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2005 VL 28 IS 7 BP 1630 EP 1635 DI 10.2337/diacare.28.7.1630 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800014 PM 15983312 ER PT J AU Pitteloud, N Mootha, VK Dwyer, AA Hardin, M Lee, H Eriksson, KF Tripathy, DJ Yialamas, M Groop, L Elahi, D Hayes, FJ AF Pitteloud, N Mootha, VK Dwyer, AA Hardin, M Lee, H Eriksson, KF Tripathy, DJ Yialamas, M Groop, L Elahi, D Hayes, FJ TI Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men SO DIABETES CARE LA English DT Article ID HORMONE-BINDING GLOBULIN; MIDDLE-AGED MEN; DEPENDENT DIABETES-MELLITUS; BODY-FAT DISTRIBUTION; HEALTHY ADULT MEN; SEX-HORMONES; SERUM TESTOSTERONE; OLDER MEN; ANDROGEN DEFICIENCY; ARTERIAL STIFFNESS AB OBJECTIVE - The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men, RESEARCH DESIGN AND METHODS - A total of 60 men (mean age 60.5 +/- 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured Using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (Vo(2max)) and expression of oxidative phosphorylation gene,, in skeletal muscle, RESULTS - A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI > 25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50) this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with (Vo(2max),11 0 = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). CONCLUSIONS - These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Lund Univ, Univ Hosp MAS, Wallenberg Lab, Dept Endocrinol, Malmo, Sweden. Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA 01605 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM fhayes@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [K23 DK 02858-04, R03 DK064276-01] NR 55 TC 202 Z9 209 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 JUL PY 2005 VL 28 IS 7 BP 1636 EP 1642 DI 10.2337/diacare.28.7.1636 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800015 PM 15983313 ER PT J AU Jackson, SL Scholes, D Boyko, EJ Abraham, L Fihn, SD AF Jackson, SL Scholes, D Boyko, EJ Abraham, L Fihn, SD TI Urinary incontinence and diabetes in postmenopausal women SO DIABETES CARE LA English DT Article ID NORWEGIAN EPINCONT; TRACT-INFECTION; BLADDER DYSFUNCTION; RESIDUAL URINE; RISK-FACTORS; HEALTH; IMPACT; AGE; EPIDEMIOLOGY; ASSOCIATION AB OBJECTIVE- This study evaluates diabetes characteristics and other risk factors for urinary incontinence among community-dwelling post menopausal women. RESEARCH DESIGN AND METHODS - We performed a cross-sectional analyst of a population-based study of 1,017 postmenopausal women (218 with diabetes), aged 55-75 years, enrolled from a health maintenance organization, Outcomes included any incontinence and severe incontinence in the prior month, RESULTS - Overall, 60% of women had any incontinence in the prior month and 8% had severe incontinence. parity and postvoid residual bladder volume were not associated with Incontinence, Oral estrogen and vaginal estrogen use were positively associated with a report of any incontinence but not severe incontinence, A history of urinary tract infection (UTI) and measures of general health were associated with both outcomes. Women with diabetes reported disproportionately more severe incontinence, difficulty controlling urination, mixed (stress and urge) incontinence, use of pads, inability to Completely empty the bladder, being unaware of leakage, and discomfort with urination (P <= 0.06). Diabetes duration, treatment type peripheral neuropathy, and retinopathy were significantly associated with severe incontinence in multiple regression models adjusted for age, education, and history of UTI (P = 0.01-0.06) ; however additional adjustment for BMI diminished the strength of association (P = 0.17-0.52). CONCLUSIONS- Urinary incontinence is highly prevalent among postmenopausal women. Women with diabetes are more likely to experience severe and symptomatic urinary incontinence. UTI history is a major risk factor, postvoid residual bladder volume plaids no demonstrable role, and BMI confounds the relationship between diabetes and incontinence among healthy postmenopausal women. C1 Univ Washington, Dept Med, VA Puget Sound, NW Hlth Serv Res Dev Program, Seattle, WA 98103 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Jackson, SL (reprint author), Univ Washington, Dept Med, VA Puget Sound, NW Hlth Serv Res Dev Program, 1825 N 52nd St, Seattle, WA 98103 USA. EM sljack@u.washington.edu FU NIDDK NIH HHS [R01 DK43134] NR 35 TC 57 Z9 60 U1 0 U2 2 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 JUL PY 2005 VL 28 IS 7 BP 1730 EP 1738 DI 10.2337/diacare.28.7.1730 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800029 PM 15983327 ER PT J AU Weinger, K McMurrich, SJ Yi, JP Lin, S Rodriguez, M AF Weinger, K McMurrich, SJ Yi, JP Lin, S Rodriguez, M TI Psychological characteristics of frequent short-notice cancellers of diabetes medical and education appointments SO DIABETES CARE LA English DT Article ID GLYCEMIC CONTROL; NON-ATTENDANCE; MISSED APPOINTMENTS; GENERAL-PRACTICE; PATIENT C1 Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, 1 Joslin Pl, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK060115]; PHS HHS [R01-60115] NR 25 TC 12 Z9 12 U1 1 U2 3 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 JUL PY 2005 VL 28 IS 7 BP 1791 EP 1793 DI 10.2337/diacare.28.7.1791 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SG UT WOS:000230163800039 PM 15983337 ER PT J AU Rodacki, M Zajdenverg, L Tortora, RP Reis, FA Albernaz, MS Goncalves, MRB Milech, A de Oliveira, JEP AF Rodacki, M Zajdenverg, L Tortora, RP Reis, FA Albernaz, MS Goncalves, MRB Milech, A de Oliveira, JEP TI Characteristics of childhood and adult-onset type 1 diabetes in a multi-ethnic population SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE type 1 diabetes; GADA; HLA DR antigens; adult ID AGE-AT-ONSET; C-PEPTIDE; HLA-DR; MELLITUS; INSULIN; AUTOIMMUNE; IDDM; SUSCEPTIBILITY; ASSOCIATION; AUTOANTIBODIES AB Objective: To compare patients with classic type I diabetes (T1D) diagnosed in childhood and adulthood regarding clinical presentation, GADA and HLA DR B1*03/04 prevalence in a multi-ethnic population. Methods: We studied 83 Brazilian patients with classic T1D divided in 2 groups: (1) diagnosed before 20 years old (n = 42); (2) diagnosed at age 20 and up (n = 4 1). All were interviewed and blood was sampled for GADA measurement and HLA DR B1 typing. Results: The study population comprised 52 women and 31 men, 52 white and 31 non-white individuals with mean age of 29.94 (+/- 10.95) years and mean disease duration of 10.37 (+/- 7.37) years. The mean age at onset in groups I and 2 were, respectively, 11.48 and 27.2 years old. There were no significant differences between groups regarding diabetic ketoacidosis at presentation. A longer symptomatic period preceding the diagnosis was observed in group 2 (p = 0.039). The prevalence of GADA and HLA DR B1*03/04 was similar between groups. HLA DR B1*13 was significantly more common in the group 1 (p = 0.024). GADA was more prevalent among patients with HLA DR B1*03 (p = 0.02). Conclusion: In this study, T1D diagnosed in adulthood was associated with longer symptomatic period preceding diagnosis and lower prevalence of HLA DR B1*13, but there were no differences regarding ketoacidosis as a form of disease presentation, GADA (+) or HLA DR B1*03/04. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Fed Univ Rio De Janeiro, Diabet & Immunol Sect, Rio De Janeiro, Brazil. Joslin Diabet Ctr, Boston, MA 02215 USA. Diabet Sect, Stat Inst Diabet & Endocrinol, Rio De Janeiro, Brazil. RP Rodacki, M (reprint author), Fed Univ Rio De Janeiro, Diabet & Immunol Sect, Rio De Janeiro, Brazil. EM melanie.rodacki@joslin.harvard.edu NR 36 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JUL PY 2005 VL 69 IS 1 BP 22 EP 28 DI 10.1016/j.diabres.2004.11.006 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FG UT WOS:000230337300004 PM 15955384 ER PT J AU Jones, RN Craig, WA Ambrose, PG Dudley, MN Pottumarthy, S AF Jones, RN Craig, WA Ambrose, PG Dudley, MN Pottumarthy, S TI Reevaluation of Enterobacteriaceae MIC/disk diffusion zone diameter regression scattergrams for 9 beta-lactams: adjustments of breakpoints for strains producing extended spectrum beta-lactamases SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Enterobacteriaceae; beta-lactams; extended spectrum beta-lactamases ID BLOOD-STREAM INFECTIONS; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; SUSCEPTIBILITY; CEPHALOSPORIN; EPIDEMIOLOGY; BACTERIA AB Validity of the Current susceptibility breakpoint criteria for 9 beta-lactam antimicrobials and performance of proposed alternative breakpoints to improve prediction of clinical outcomes were analyzed by testing a contemporary collection of 350 Enterobacteriaceae, enriched for an overrepresentative collection of 70 (20.0%) strains producing extended-spectrum beta-lactamases (ESBLs). The majority of the strains were isolated from bloodstream infections (83.7% of the entire collection and 85.7% of the ESBL subset). The 9 beta-lactam antimicrobials analyzed were aztreonam, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and cefuroxime. Reference broth microdilution MIC results were compared with those zone diameters obtained by the standardized disk diffusion test. The correlation coefficient (r) was acceptable for all antimicrobials, ranging from 0.87 (cefotetan) to 0.97 (aztreonam, cefotaxime, and ceflazidime). Using the current susceptible breakpoint criteria for Enterobacteriaceae, the intermethod categorical agreement ranged from 90.6% (cefotaxime) to 98.0% (ceftazidime). Very major (false-susceptible by disk test) and major errors (false-resistant) were nil (0.0%) for 6 of the 9 beta-lactams. Minor error rates ranged from only 0.9% (cefotetan) to 9.4% (cefotaxime). The proposed MIC breakpoint criteria (generally lower) adjusted to levels to accurately detect ESBL-producing strains and better predict clinical outcomes, also had acceptable intermethod concordance ranging from 90.6% (cefotetan) to 100.0% (ceftazidime). Remarkably, an improvement in the intermethod categorical agreement ranging from + 1.7% to + 8.3% was observed for 7 of the 9 antimicrobials, including the ESBL index or screening compounds (aztreonam, ceftazidime, cefotaxime, and ceftriaxone). No change in the breakpoint criteria, with removal of the intermediate category was tentatively proposed for cefoxitin and cefuroxime, resulting in an increase of the serious intermethod errors (very major and major), but the absolute intermethod agreement remained highly acceptable at 90.6% to 93.4%. Although the current breakpoint criteria remain acceptable in minimizing intermethod discords, the alternative susceptible breakpoint criteria proposed by combining pharmacokinetic/pharmacodynamic (PK/PD), microbiology MIC population analyses, and clinical success parameters possess improved intermethod agreement for the ESBL screening drugs and 5 other broad-spectrum beta-lactani compounds. The Clinical Laboratory Standards Institute (formerly, the National Committee for Clinical Laboratory Standards) should consider these changes to facilitate the detection of all Enterobacteriaceae with low PK/PD target attainment rates, therefore having the potential for suboptimal responses with usual therapeutic dosing. (c) 2005 Elsevier Inc. All rights reserved. C1 JMI Labs, Beaver Kreek Ctr 345, N Liberty, IA 52317 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Inst Clin Pharmacodynam Ordway, Albany, NY USA. Diversa Pharmaceut, San Diego, CA USA. RP Jones, RN (reprint author), JMI Labs, Beaver Kreek Ctr 345, Suite A, N Liberty, IA 52317 USA. EM ronald-jones@jmilabs.com NR 23 TC 17 Z9 19 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 2005 VL 52 IS 3 BP 235 EP 246 DI 10.1016/j.diagmicrobio.2005.02.006 PG 12 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 969LW UT WOS:000232236700011 PM 16105568 ER PT J AU Sonntag, WE Carter, CS Ikeno, Y Ekenstedt, K Carlson, CS Loeser, RF Chakrabarty, S Lee, S Bennett, C Ingram, R Moore, T Ramsey, M AF Sonntag, WE Carter, CS Ikeno, Y Ekenstedt, K Carlson, CS Loeser, RF Chakrabarty, S Lee, S Bennett, C Ingram, R Moore, T Ramsey, M TI Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span SO ENDOCRINOLOGY LA English DT Article ID MALE FISCHER-344 RATS; DIETARY RESTRICTION; DWARF MICE; LONG-TERM; SPATIAL MEMORY; IGF-1; LONGEVITY; MOUSE; EXPRESSION; IMMUNE AB Disruption of the insulin/IGF-I pathway increases life span in invertebrates. However, effects of decreased IGF-I signaling in mammalian models remain controversial. Using a rodent model with a specific and limited deficiency of GH and IGF-I, we report that GH and IGF-I deficiency throughout life [ GH deficiency (GHD)] has no effect on life span compared with normal, heterozygous animals. However, treatment of GHD animals with GH from 4 - 14 wk of age [adult-onset (AO) GHD] increased median and maximal life span by 14% and 12%, respectively. Analysis of end-of-life pathology indicated that deficiency of these hormones decreased tumor incidence in GHD and AO-GHD animals ( 18 and 30%, respectively) compared with heterozygous animals and decreased the severity of, and eliminated deaths from, chronic nephropathy. Total disease burden was reduced by 24% in GHD and 16% in AO-GHD animals. Interestingly, the incidence of intracranial hemorrhage increased by 154 and 198% in GHD and AO-GHD animals, respectively, compared with heterozygous animals. Deaths from intracranial hemorrhage in AO-GHD animals were delayed by 14 wk accounting for the increased life span compared with GHD animals. The presence of GH and IGF-I was necessary to maximize reproductive fitness and growth of offspring early in life and to maintain cognitive function and prevent cartilage degeneration later in life. The diverse effects of GH and IGF-I are consistent with a model of antagonistic pleiotropy and suggest that, in response to a deficiency of these hormones, increased life span is derived at the risk of functional impairments and tissue degeneration. C1 Wake Forest Univ Hlth Sci, Dept Physiol, Winston Salem, NC 27012 USA. Wake Forest Univ Hlth Sci, Dept Pharmacol, Winston Salem, NC 27012 USA. Wake Forest Univ Hlth Sci, Sticht Ctr Aging, Winston Salem, NC 27012 USA. Wake Forest Univ Hlth Sci, Roena Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27012 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res Serv, San Antonio, TX 78229 USA. Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USA. Rush Med Coll, Dept Med, Chicago, IL 60612 USA. Rush Med Coll, Dept Biochem, Chicago, IL 60612 USA. Univ Texas, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. RP Sonntag, WE (reprint author), Wake Forest Univ Hlth Sci, Dept Physiol & Pharmacol, 1 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM wsonntag@wfubmc.edu RI Carter, Christy/A-6828-2011; Carter, Christy/E-6630-2011 FU NIA NIH HHS [R01AG19392, 5P60AG10484, P01 AG011370, P01AG11370, R01 AG019392] NR 67 TC 78 Z9 78 U1 1 U2 4 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 JUL PY 2005 VL 146 IS 7 BP 2920 EP 2932 DI 10.1210/en.2005-0058 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935HZ UT WOS:000229772700008 PM 15790724 ER PT J AU Kogai, T Kanamoto, Y Li, AI Che, LH Ohashi, E Taki, K Chandraratna, RA Saito, T Brent, GA AF Kogai, T Kanamoto, Y Li, AI Che, LH Ohashi, E Taki, K Chandraratna, RA Saito, T Brent, GA TI Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells SO ENDOCRINOLOGY LA English DT Article ID TRANS-RETINOIC ACID; SODIUM-IODIDE SYMPORTER; RAT-THYROID CELLS; MESSENGER-RNA; RADIOIODIDE UPTAKE; FRTL-5 CELLS; 13-CIS-RETINOIC ACID; INDUCE APOPTOSIS; CARCINOMA-CELLS; MAMMARY-GLAND AB The sodium/iodide symporter (NIS) mediates iodide uptake in lactating breast tissue and is expressed in some breast cancers. We have previously demonstrated that all-trans retinoic acid (tRA) stimulates NIS gene expression and the selective cytotoxic effect of beta-emitting radioiodide-131 (I-131) in both in vitro and in vivo MCF-7 breast cancer cell systems. We studied the ability of natural and synthetic retinoids, in combination with other nuclear receptor ligands, to achieve greater and more sustained induction of NIS in MCF-7 cells and enhance I-131-mediated cytotoxicity. Selective stimulation of retinoic acid receptor (RAR) beta/gamma produced marked NIS induction; and selective stimulation of RAR alpha, RAR gamma, or retinoid X receptor produced more modest induction. Maximal NIS induction was seen with 9-cis retinoic acid and AGN190168, a RAR beta/gamma-agonist. Dexamethasone (Dex), but not the other nuclear receptor ligands, in combination with tRA synergistically induced iodide uptake and NIS mRNA expression, predominantly by prolonging NIS mRNA half-life. The addition of Dex reduced the EC50 of tRA for NIS stimulation to approximately 7%, such that 10(-7) M tRA with addition of Dex enhanced iodide uptake and selective cytotoxicity of I-131 greater than 10(-6) M tRA alone. AGN190168 combined with Dex synergistically increased iodide uptake and significantly prolonged induction (5 d) of iodide uptake compared with that induced by the combination of tRA/Dex or 9-cis retinoic acid/Dex. The addition of Dex reduced the effective dose of retinoid and prolonged the induction of NIS, especially with AGN190168, suggesting higher efficacy of I-131 after combination treatment. C1 Univ Calif Los Angeles, David Geffen Sch med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Physiol,Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Vitae Pharmaceut, Irvine, CA 92618 USA. Univ Yamanashi, Dept Med 3, Yamanashi 4093898, Japan. RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NCI NIH HHS [CA89364] NR 62 TC 37 Z9 37 U1 1 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 JUL PY 2005 VL 146 IS 7 BP 3059 EP 3069 DI 10.1210/en.2004-1334 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935HZ UT WOS:000229772700024 PM 15817668 ER PT J AU Rosner, BA Colditz, GA Webb, PM Hankinson, SE AF Rosner, BA Colditz, GA Webb, PM Hankinson, SE TI Mathematical models of ovarian cancer incidence SO EPIDEMIOLOGY LA English DT Article ID NATIONAL DEATH INDEX; BREAST-CANCER; RISK-FACTORS; REPRODUCTIVE FACTORS; AGE; PROGESTERONE; MENOPAUSE; PREGNANCY; OVULATION; WOMEN AB Background: Pike has proposed "protected time" as one summary method for modeling reproductive risk factors in relation to ovarian cancer incidence. We evaluate this and other approaches to summarizing risk for ovarian cancer. Methods: We identified 472 incident cases of ovarian cancer during 2,298,068 person-years of follow-up of 24- to 55-year-old premenopausal women at cohort inception. Reproductive exposures, use of oral contraceptives, and history of tubal ligation were evaluated. Results: Age at menopause is directly related to cumulative risk of ovarian cancer up to age 70 years (age 55 vs. age 45, risk increase = 62%; 95% confidence interval = 36 to 96%) and age at menarche is inversely related to risk (age 15 vs. 11, risk reduction = 3 1 %; 27-34%). Use of oral contraceptives for 5 years before age 30 decreases risk of ovarian cancer to age 70 by 37% (32 to 41%). Tubal ligation reduces risk up to age 70 by 21% (-2 to 38%). Parity reduces risk, independent of age at first birth and age at last birth. A model summarizing years of ovulation offers a fit comparable to a more complex modeling of reproductive variables. The model fit is good, with a concordance statistic of 0.60 (0.57 to 0.62) indicating reasonable ability to differentiate those who will develop ovarian cancer from those who will remain disease free. Conclusion: This model may be applied in the identification of women at high risk for ovarian cancer, for example, in selecting candidates for prevention trials. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. RP Rosner, BA (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM Bemard.Rosner@channing.harvard.edu RI Webb, Penelope/D-5736-2013; Colditz, Graham/A-3963-2009 OI Webb, Penelope/0000-0003-0733-5930; Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385, CA87969] NR 32 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 508 EP 515 DI 10.1097/01.ede.0000164557.81694.63 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000012 PM 15951669 ER PT J AU de Vries, P Humphrey, A McCartney, D Prather, P Bolton, P Hunt, A AF de Vries, P Humphrey, A McCartney, D Prather, P Bolton, P Hunt, A CA TSC Behaviour Consensus Panel TI Consensus clinical guidelines for the assessment of cognitive and behavioural problems in Tuberous Sclerosis SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Tuberous Sclerosis; clinical guidelines; cognition behaviour ID LEARNING-DISABILITY; ATTENTION DEFICITS; CHILDREN; COMPLEX; DISORDERS; EPILEPSY; AUTISM; HEALTH AB Tuberous Sclerosis (TSC) is a genetic disorder characterised by abnormal growths in a wide range of organs. In the brain, abnormalities of differentiation, proliferation and migration can produce a range of neuropsychiatric features such as mental retardation, autism and ADHD. Although these manifestations are not diagnostic of the disorder, cognitive and behavioural features are often of greatest concern to families yet limited clinical assessment and interventions are currently offered. A consensus panel at a TSC Brain/Behaviour workshop recommended that the cognitive and behavioural profiles of individuals with TSC should be assessed at regular intervals in a planned fashion in accordance with the difficulties associated with the disorder. Evaluations should include the use of standardised neuropsychological and behavioural tools as appropriate to the age and developmental level of the individual assessed. These cognitive and behavioural profiles should be incorporated in the overall formulation of the needs of the person with TSC to plan educational, social and clinical management strategies. Assessments should be documented so that individual longitudinal progress can be monitored. The paper outlines the problems associated with TSC, the purpose of recommended assessments, developmentally appropriate stages for assessment, and identifies specific areas that should be targeted for assessment. C1 TB Sclerosis Assoc, N Leigh OX29 6TX, Witney, England. Inst Psychiat, Child & Adolescent Psychiat Dept, London, England. Inst Psychiat, MRC, Ctr Social Genet & Dev Psychiat, London, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Cambridge, Dev Psychiat Sect, Cambridge, England. RP Hunt, A (reprint author), TB Sclerosis Assoc, Church Farm House,Church Rd, N Leigh OX29 6TX, Witney, England. EM research@tuberous-sclerosis.org RI Bolton, Patrick/E-8501-2010 OI Bolton, Patrick/0000-0002-5270-6262 NR 41 TC 40 Z9 42 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD JUL PY 2005 VL 14 IS 4 BP 183 EP 190 DI 10.1007/s00787-005-0443-1 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 943ZU UT WOS:000230395500001 PM 15981129 ER PT J AU Mauch, P Ng, A Aleman, B Carde, P Constine, L Diehl, V Dinshaw, K Gospodarowicz, M Hancock, S Hodgson, D Hoppe, R Liang, R Loeffler, M Specht, L Travis, LB Wirth, A Yahalom, J AF Mauch, P Ng, A Aleman, B Carde, P Constine, L Diehl, V Dinshaw, K Gospodarowicz, M Hancock, S Hodgson, D Hoppe, R Liang, R Loeffler, M Specht, L Travis, LB Wirth, A Yahalom, J TI Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Hodgkins Disease CY SEP 18-21, 2004 CL Cologne, GERMANY SP German Hodgkin Study Grp DE Hodgkin's disease; cancer survivors; complications ID ESTROGEN PLUS PROGESTIN; MEDIASTINAL RADIATION-THERAPY; HEALTHY POSTMENOPAUSAL WOMEN; BREAST-CANCER; PNEUMOCOCCAL VACCINE; ANTIBODY-RESPONSES; CARDIAC TOXICITY; CHEMOTHERAPY; RADIOTHERAPY; TRIAL AB A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Inst Gustave Roussy, Villejuif, France. Univ Rochester, Rochester, NY USA. Univ Cologne, Cologne, Germany. Tata Mem Hosp, Bombay, Maharashtra, India. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Stanford Univ, Palo Alto, CA 94304 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Univ Leipzig, D-7010 Leipzig, Germany. Univ Copenhagen, DK-1168 Copenhagen, Denmark. NIH, Rockville, MD USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mauch, P (reprint author), 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 47 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 2005 VL 75 SU 66 BP 68 EP 76 PG 9 WC Hematology SC Hematology GA 932YT UT WOS:000229591400012 ER PT J AU Canellos, GP AF Canellos, GP TI Clinical trials in North America SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Hodgkins Disease CY SEP 18-21, 2004 CL Cologne, GERMANY SP German Hodgkin Study Grp DE Hodgkin Lymphoma trials; intergroup trials; salvage therapy; new drugs ID ANTI-CD30 MONOCLONAL-ANTIBODY; RELAPSED HODGKINS-DISEASE; STEM-CELL TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; LONG-TERM SURVIVORS; BEACOPP CHEMOTHERAPY; 2ND MALIGNANCY; FOLLOW-UP; PHASE-II; LYMPHOMA AB Majority of patients with Hodgkin lymphoma are cured with current therapy. The short and long-term toxicity of therapy is a current issue, most especially the radiation-induced second tumors and cardiac abnormalities. Optimal therapy of advanced disease is being compared to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). More intensive chemotherapy may result in higher response but greater toxicity. Regimens requiring radiotherapy are also at risk of long-term toxicity. New targeted biologic therapy is under current investigation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 24 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 2005 VL 75 SU 66 BP 121 EP 124 PG 4 WC Hematology SC Hematology GA 932YT UT WOS:000229591400020 ER PT J AU Brun, ACM Miyake, N Magnusson, M Miyake, K Scadden, DT Karlsson, S AF Brun, ACM Miyake, N Magnusson, M Miyake, K Scadden, DT Karlsson, S TI HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Univ Lund Hosp, Lund Stem Cell Ctr, S-22185 Lund, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr AIDS Res, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 15 BP 41 EP 41 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100012 ER PT J AU Zorn, E Kim, HT Lee, SJ Floyd, BH Litsa, D Arumugarajah, S Bellucci, R Antin, JH Soiffer, RJ Ritz, J AF Zorn, E Kim, HT Lee, SJ Floyd, BH Litsa, D Arumugarajah, S Bellucci, R Antin, JH Soiffer, RJ Ritz, J TI Chronic graft-versus-host disease correlates with reduced frequency of FOXP3+CD4+CD25+regulatory T cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 41 BP 47 EP 48 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100035 ER PT J AU Wagers, A AF Wagers, A TI Hematopoietic and myogenic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 66 BP 54 EP 54 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100060 ER PT J AU Lee, J Fukumoto, H Orne, J Klucken, J Raju, S Vanderburg, CR Irizarry, MC Hyman, BT Ingelsson, M AF Lee, J Fukumoto, H Orne, J Klucken, J Raju, S Vanderburg, CR Irizarry, MC Hyman, BT Ingelsson, M TI Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms SO EXPERIMENTAL NEUROLOGY LA English DT Article DE BDNF; Alzheimer's disease; ELISA; gene polymorphisms; association studies; synaptophysin ID NEUROTROPHIC FACTOR BDNF; ACTIVITY-DEPENDENT SECRETION; FACTOR GENETIC-POLYMORPHISM; VAL66MET POLYMORPHISM; BIPOLAR DISORDER; HUMAN-MEMORY; BRAIN; DISEASE; ASSOCIATION; ONSET AB Levels of brain-derived neurotrophic factor (BDNF) are reduced in specific brain regions in Alzheimer's disease (AD) and BDNF gene polymorphisms have been suggested to influence AD risk, hippocampal function, and memory. We investigated whether the polymorphisms at the BDNF 196 and 270 loci were associated with AD in a clinical and neuropathological cohort of 116 AD cases and 77 control subjects. To determine how BDNF protein levels relate to BDNF polymorphisms and AD pathology, we also measured BDNF in temporal association cortex, frontal association cortex, and cerebellum in 57 of the AD and 21 control cases. BDNF protein levels in temporal neocortex of the AD brains were reduced by 33% compared to control brains, whereas levels were unchanged in frontal and cerebellar cortex. The BDNF genotypes were not significantly associated with a diagnosis of AD, although the BDNF 270 C allele was slightly overrepresented among carriers of the APOE epsilon 4 allele. Moreover, BDNF protein levels did not differ between the various BDNF genotypes and alleles. Neuropathologically, the loss of BDNF in AD showed a weak correlation with accumulation of neuritic amyloid plaques and loss of the neuronal/synaptic marker synaptophysin. The results suggest that the investigated BDNF polymorphisms are neither robust genetic risk factors nor determinants of BDNF protein levels in AD. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 114 16th St, Charlestown, MA 02129 USA. EM BHyman@partners.org FU NIA NIH HHS [AG 05134] NR 25 TC 56 Z9 61 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2005 VL 194 IS 1 BP 91 EP 96 DI 10.1016/j.expneurol.2005.01.026 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 929ZI UT WOS:000229385000008 PM 15899246 ER PT J AU Lee, JM Li, J Johnson, DA Stein, TD Kraft, AD Calkins, MJ Jakel, RJ Johnson, JA AF Lee, JM Li, J Johnson, DA Stein, TD Kraft, AD Calkins, MJ Jakel, RJ Johnson, JA TI Nrf2, a multi-organ protector? SO FASEB JOURNAL LA English DT Article DE Nrf2; ARE; multi-organ protection ID ANTIOXIDANT RESPONSE ELEMENT; PROTEIN-KINASE-C; YA-SUBUNIT GENE; OXIDATIVE STRESS; INDUCIBLE EXPRESSION; NF-E2-RELATED FACTOR-2; TRANSCRIPTION FACTOR; MICROARRAY ANALYSIS; OLIGONUCLEOTIDE MICROARRAY; OXIDOREDUCTASE-1 GENE AB NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that binds to the promoter sequence "antioxidant responsive element (ARE)" leading to coordinated up-regulation of ARE-driven detoxification and antioxidant genes. Since the expression of a wide array of antioxidant and detoxification genes are positively regulated by the ARE sequence, Nrf2 may serve as a master regulator of the ARE-driven cellular defense system against oxidative stress. In support of this, numerous studies have shown that Nrf2 protects many cell types and organ systems from a broad spectrum of toxic insults and disease pathogenesis. This Nrf2-conferred, multi-organ protection phenomenon raises an interesting question about how a single protein can protect many different organs from various toxic insults. A possible molecular mechanism explaining this phenomenon is that Nrf2 protects many different cell types by coordinately up-regulating classic ARE-driven genes as well as cell type-specific target genes that are required for the defense system of each cell type in its unique environment. This hypothesis is supported by microarray data indicating the protective role of Nrf2 is conveyed through both known ARE-driven genes and novel cell type-specific genes. The widespread nature of Nrf2 may have an important therapeutic potential, allowing prevention of carcinogenesis and neurodegenerative diseases. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. Univ Wisconsin, Neurosci Training Program, Madison, WI 53705 USA. Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. Univ Wisconsin, Ctr Neurosci, Madison, WI 53705 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Univ Wisconsin, Sch Pharm, 6125 Rennebohm Hall,777 Highland Ave, Madison, WI 53705 USA. EM jajohnson@pharmacy.wisc.edu FU CSRD VA [I01 CX001038] NR 43 TC 248 Z9 258 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JUL PY 2005 VL 19 IS 9 BP 1061 EP 1066 DI 10.1096/fj.04-2591hyp PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 951IO UT WOS:000230923000034 PM 15985529 ER PT J AU Yoshida, K Yamaguchi, T Kufe, D Miki, Y AF Yoshida, K Yamaguchi, T Kufe, D Miki, Y TI JNK phosphorylation of 14-3-3 regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Genet, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM yos.mgen@mri.tmd.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 48 EP 48 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100164 ER PT J AU Gooz, M Gooz, P Raymond, JR AF Gooz, M Gooz, P Raymond, JR TI Serotonin-induced ERK phosphorylation involves ADAM-17/TACE activation in mesangial cells SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. EM beckm@musc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 180 EP 180 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101142 ER PT J AU Paszty, K Antalffy, G Penheiter, AR Homolya, L Padanyi, R Ilias, A Filoteo, AG Penniston, JT Enyedi, A AF Paszty, K Antalffy, G Penheiter, AR Homolya, L Padanyi, R Ilias, A Filoteo, AG Penniston, JT Enyedi, A TI The caspase-3 cleavage product of PMCA4b is activated and is targeted to the basolateral membrane of polarized MDCKII cells SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Hungarian Acad Sci, Membrane Res Grp, Budapest, Hungary. Natl Med Ctr, Budapest, Hungary. Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN USA. Hungarian Acad Sci, Inst Enzimol, Budapest, Hungary. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. EM paszty@biomembrane.hu RI Enyedi, Agnes/N-9742-2013; Homolya, Laszlo/N-1154-2016 OI Enyedi, Agnes/0000-0002-7366-9376; NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 197 EP 197 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101198 ER PT J AU Penheiter, AR Filoteo, AG Penniston, JT Caride, AJ AF Penheiter, AR Filoteo, AG Penniston, JT Caride, AJ TI Correlation of structure with kinetics in activation of PMCA by calmodulin SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Membrane Biol,Neurosurg Serv, Boston, MA USA. EM john@penniston.com NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 198 EP 199 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101203 ER PT J AU Leung, FW Lieberman, J Fagen, N Kasimian, D Wick, R AF Leung, FW Lieberman, J Fagen, N Kasimian, D Wick, R TI Colonoscopic features of simvastatin-induced colitis suggest ischemia as an etiologic mechanism SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; BLOOD-FLOW; COLON; ATORVASTATIN; THERAPY C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Leung, FW (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Sepulveda Ambulatory Care Ctr, Res & Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. NR 25 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2005 VL 62 IS 1 BP 175 EP 178 AR PII S0016-5107(05)00503-1 DI 10.1016/S0016-5107(05)00503-1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 944ZQ UT WOS:000230470300036 PM 15990847 ER PT J AU Hamilton, B Doug, YQ Shindo, M Liu, WY Odell, I Ruvkun, G Lee, SS AF Hamilton, B Doug, YQ Shindo, M Liu, WY Odell, I Ruvkun, G Lee, SS TI A systematic RNAi screen for longevity genes in C-elegans SO GENES & DEVELOPMENT LA English DT Article DE longevity; aging; C. elegans; insulin signaling; RNAi screen; genomic ID EXTENDS LIFE-SPAN; AGE-1 PI3 KINASE; CAENORHABDITIS-ELEGANS; INSULIN-RECEPTOR; TRANSCRIPTION FACTORS; OXIDATIVE STRESS; METABOLIC-RATE; FAMILY-MEMBER; PROTEIN; DAF-16 AB We report here the first genome-wide functional genomic screen for longevity genes. We systematically surveyed Caenorhabditis elegans genes using large-scale RNA interference (RNAi), and found that RNAi inactivation of 89 genes extend C. elegans lifespan. Components of the daf-2/insulin-like signaling pathway are recovered, as well as genes that regulate metabolism, signal transduction, protein turnover, and gene expression. Many of these candidate longevity genes are conserved across animal phylogeny. Genetic interaction analyses with the new longevity genes indicate that some act upstream of the daf-16/FOXO transcription factor or the sir2.1 protein deacetylase, and others function independently of daf-16/FOXO and sir2.1, and might define new pathways to regulate lifespan. C1 Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Lee, SS (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 USA. EM SSL29@cornell.edu RI Liu, Wenyu/C-2781-2014; OI Liu, Wenyu/0000-0002-0244-3038; Odell, Ian/0000-0003-3990-6929 NR 56 TC 267 Z9 316 U1 9 U2 41 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 JUL 1 PY 2005 VL 19 IS 13 BP 1544 EP 1555 DI 10.1101/gad.1308205 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 943EH UT WOS:000230334600005 PM 15998808 ER PT J AU Dannenberg, JH David, G Zhong, S van der Torre, J Wong, WH DePinho, RA AF Dannenberg, JH David, G Zhong, S van der Torre, J Wong, WH DePinho, RA TI mSin3A corepressor regulates diverse transcriptional networks governing normal and neoplastic growth and survival SO GENES & DEVELOPMENT LA English DT Article DE histone modifications; knock-out; mSin3 complex; mSin3A; transcriptional regulation; tumorigenesis ID CANDIDATE TUMOR-SUPPRESSOR; HISTONE DEACETYLASE; SACCHAROMYCES-CEREVISIAE; REPRESSES TRANSCRIPTION; FISSION YEAST; IN-VIVO; COMPLEX; PROTEIN; P53; GENE AB mSin3A is a core component of a large multiprotein corepressor complex with associated histone deacetylase (HDAC) enzymatic activity. Physical interactions of mSin3A with many sequence-specific transcription factors has linked the mSin3A corepressor complex to the regulation of diverse signaling pathways and associated biological processes. To dissect the complex nature of mSin3A's actions, we monitored the impact of conditional mSin3A deletion on the developmental, cell biological, and transcriptional levels. mSin3A was shown to play an essential role in early embryonic development and in the proliferation and survival of primary, immortalized, and transformed cells. Genetic and biochemical analyses established a role for mSin3A/HDAC in p53 deacetylation and activation, although genetic deletion of p53 was not sufficient to attenuate the mSin3A null cell lethal phenotype. Consistent with mSin3A's broad biological activities beyond regulation of the p53 pathway, time-course gene expression profiling following mSin3A deletion revealed deregulation of genes involved in cell cycle regulation, DNA replication, DNA repair, apoptosis, chromatin modifications, and mitochondrial metabolism. Computational analysis of the mSin3A transcriptome using a knowledge-based database revealed several nodal points through which mSin3A influences gene expression, including the Myc-Mad, E2F, and p53 transcriptional networks. Further validation of these nodes derived from in silico promoter analysis showing enrichment for Myc-Mad, E2F, and p53 cis-regulatory elements in regulatory regions of up-regulated genes following mSin3A depletion. Significantly, in silico promoter analyses also revealed specific cis-regulatory elements binding the transcriptional activator Stat and the ISWI ATP-dependent nucleosome remodeling factor Falz, thereby expanding further the mSin3A network of regulatory factors. Together, these integrated genetic, biochemical, and computational studies demonstrate the involvement of mSin3A in the regulation of diverse pathways governing many aspects of normal and neoplastic growth and survival and provide an experimental framework for the analysis of essential genes with diverse biological functions. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI , gregory/0000-0002-3371-4558 FU NCI NIH HHS [R01 CA086379, R01CA86379]; NIGMS NIH HHS [GM67250, R01 GM067250] NR 77 TC 118 Z9 120 U1 1 U2 6 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 JUL 1 PY 2005 VL 19 IS 13 BP 1581 EP 1595 DI 10.1101/gad.1286905 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 943EH UT WOS:000230334600008 PM 15998811 ER PT J AU Rottbauer, W Just, S Wessels, G Trano, N Most, P Katus, HA Fishman, MC AF Rottbauer, W Just, S Wessels, G Trano, N Most, P Katus, HA Fishman, MC TI VEGF-PLC gamma 1 pathway controls cardiac contractility in the embryonic heart SO GENES & DEVELOPMENT LA English DT Article DE VEGF; PLC gamma 1; contractility; heart; zebrafish ID ENDOTHELIAL-GROWTH-FACTOR; LENGTH-TENSION RELATION; FACTOR VEGF; CARDIOVASCULAR DEVELOPMENT; ZEBRAFISH EMBRYOS; PLC-GAMMA; MYOCYTES; MUSCLE; VASCULOGENESIS; ANGIOGENESIS AB The strength of the heart beat can accommodate in seconds to changes in blood pressure or flow. The mechanism for such homeostatic adaptation is unknown. We sought the cause of poor contractility in the heart of the embryonic zebrafish with the mutation dead beat. We find through cloning that this is due to a mutation in the phospholipase C gamma 1 (plc gamma 1) gene. In mutant embryos, contractile function can be restored by PLC gamma 1 expression directed selectively to cardiac myocytes. In other situations, PLC gamma 1 is known to transduce the signal from vascular endothelial growth factor (VEGF), and we show here that abrogation of VEGF also interferes with cardiac contractility. Somewhat unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same system functions in the rat. Blockage of VEGF-PLC gamma 1 signaling decreases calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a positive inotropic effect on cardiomyocytes by increasing calcium transients. Thus, the muscle of the heart uses the VEGF-PLC gamma 1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility. C1 Univ Heidelberg, Dept Med 3, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Fishman, MC (reprint author), Univ Heidelberg, Dept Med 3, Neuenheimer Feld 230, D-69120 Heidelberg, Germany. EM wolfgang.rottbauer@med.uni-heidelberg.de; mark.fishman@pharma.novartis.com RI Katus, Hugo/P-1712-2016 FU NHLBI NIH HHS [5R01HL49579, 1R01HL63206]; NIDDK NIH HHS [5R01DK55383] NR 49 TC 78 Z9 81 U1 2 U2 6 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 JUL 1 PY 2005 VL 19 IS 13 BP 1624 EP 1634 DI 10.1101/gad.1319405 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 943EH UT WOS:000230334600011 PM 15998812 ER PT J AU Navarro, RE Blackwell, TK AF Navarro, RE Blackwell, TK TI Requirement for P granules and meiosis for accumulation of the germline RNA helicase CGH-1 SO GENESIS LA English DT Article DE germ cell; germline; stem cell; Caenorhabditis elegans; apoptosis; meiosis; RNA helicase; P granule; P body; CGH-1 ID CAENORHABDITIS-ELEGANS GERMLINE; C-ELEGANS; MESSENGER-RNA; TRANSLATIONAL REPRESSION; MEIOTIC PROPHASE; GLD-1; CELL; PROTEIN; APOPTOSIS; PATHWAY AB In Caenorhabditis elegans, lack of the conserved germline RNA helicase CGH-1 causes infertility and excessive levels of physiological germline apoptosis, a process that normally claims about half of all developing oocytes. In yeast the CGH-1 ortholog is a key component of degradative "processing (P) bodies," which may share some properties with germline protein-RNA complexes such as P granules. During oogenesis CGH-1 associates with P granules, but also accumulates to high levels in additional cytoplasmic particles. Here we show that appropriate levels and localization of CGH-1 depends on some P granule components and on mechanisms that establish meiotic development. At the same time, germ cell death is not increased by various abnormalities in P granules or meiosis. We conclude that in developing oocytes CGH-1 particles accumulate specifically in response to meiotic development and have distinct functions from P granules, and may be dynamic protein-mRNA structures. C1 Harvard Univ, Sch Med, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Univ Nacl Autonoma Mexico, Dept Biol Celular, Inst Fisiol Celular, Mexico City, DF, Mexico. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu NR 38 TC 19 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2005 VL 42 IS 3 BP 172 EP 180 DI 10.1002/gene.20136 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 950CT UT WOS:000230835900005 PM 15986473 ER PT J AU Won, JS Im, YB Khan, M Singh, AK Singh, I AF Won, JS Im, YB Khan, M Singh, AK Singh, I TI Involvement of phospholipase A(2) and lipoxygenase in lipopolysaccharide-induced inducible nitric oxide synthase expression in glial cells SO GLIA LA English DT Article DE PLA(2); COX; 5-LO; 12-LO; iNOS; NF kappa B; nitric oxide; glial cells ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; HUMAN-NEUTROPHILS; ARACHIDONIC-ACID; PHOSPHATIDATE PHOSPHOHYDROLASE; NORDIHYDROGUAIARETIC ACID; P388D(1) MACROPHAGES; MULTIPLE-SCLEROSIS; BROMOENOL LACTONE AB The present study underlines the importance of phospholipase A(2) (PLA(2))- and lipoxygenase (LO)-mediated signaling processes in the regulation of inducible nitric oxide synthase (iNOS) gene expression. In glial cells, lipopolysaccharide (LPS) induced the activities of PLA(2) (calcium-independent PLA(2); iPLA(2) and cytosolic PLA(2); cPLA(2)) as well as gene expression of iNOS. The inhibition of cPLA(2) by methyl arachidonyl fluorophosphates (MAFP) or antisense oligomer against cPLA(2) and inhibition of iPLA2 by bromoenol lactone reduced the LPS-induced iNOS gene expression and NF kappa B activation. In addition, the inhibition of LO by nordihydroguaiaretic acid (NDGA; general LO inhibitor) or MK886 (5-LO inhibitor), but not baicalein (12-LO inhibitor), completely abrogated the LPS-induced iNOS expression. Because NDGA could abrogate the LPS-induced activation of NF kappa B, while MK886 had no effect on it, LO-mediated inhibition of iNOS gene induction by LPS may involve an NF kappa B-dependent or -independent (by 5-LO) pathway. In contrast to LO, however, the cyclooxygenase (COX) may not be involved in the regulation of LPS-mediated induction of iNOS gene because COX inhibition by indomethacin (general COX nhibitor), SC560 (COX-1 inhibitor), and NS398 (COX-2 inhibitor) affected neither the LPS-induced iNOS expression nor activation of NF kappa B. These results indicate a role for cPLA(2) and iPLA(2) in LPS-mediated iNOS gene induction glial cells and the involvement of LO in these reactions. (C) 2005 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Lab Med Serv, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,Clin Sci Bldg,Room 316, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766] NR 58 TC 16 Z9 18 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD JUL PY 2005 VL 51 IS 1 BP 13 EP 21 DI 10.1002/glia.20178 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 934IZ UT WOS:000229703800002 PM 15779087 ER PT J AU Kwak, EL Moberg, KH Wahrer, DCR Quinn, JE Gilmore, PM Graham, CA Hariharan, IK Harkin, DP Haber, DA Bell, DW AF Kwak, EL Moberg, KH Wahrer, DCR Quinn, JE Gilmore, PM Graham, CA Hariharan, IK Harkin, DP Haber, DA Bell, DW TI Infrequent mutations of Archipelago (hAGO, hCDC4, Fbw7) in primary ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Archipelago; ovarian tumor; cyclin E; c-Myc; mutation ID F-BOX PROTEIN; CYCLIN-E; C-MYC; CHROMOSOMAL INSTABILITY; ENDOMETRIAL CANCER; UBIQUITIN LIGASE; DEGRADATION; DROSOPHILA; EXPRESSION; SEL-10 AB Objective. Archipelago (AGO, also known as hCdc4, Fbw7, or Sel-10) is an F-box containing component of the SCF complex implicated in the ubiquitination and proteolysis of cyclin E and c-Myc, and found to be mutated in 16% of endometrial carcinomas. We have previously reported somatic mutations in AGO in 3/10 ovarian cancer cell lines, but the frequency of such mutations in primary ovarian cancer is unknown. Methods. The coding sequence of AGO was analyzed in 95 primary sporadic ovarian tumors and 16 cases of familial ovarian cancer, and correlated with levels of cyclin E and c-Myc protein expression. Constructs encoding mutations in AGO were transfected into an AGO-null cell line to directly test their ability to regulate cyclin E and c-Myc levels. Results. Mutations were present in only 2 of 95 sporadic cases: a premature stop within the WD domain (471 Ter) and a missense change near the F-box (S245T). Both primary tumor specimens containing these mutations showed high levels of cyclin E and c-Myc, but reconstitution of an AGO-null cell line with constructs encoding these mutations showed 471 Ter to be inactive in regulating endogenous cyclin E and c-Myc levels, while the S245T mutant was indistinguishable from wild-type. No germ-line mutations were found in familial cases of ovarian cancer. Conclusion. Somatic AGO mutations are infrequent in primary ovarian cancers and are unlikely to contribute to familial ovarian cancer. Reconstitution experiments, rather than measuring tumor levels of cyclin E and c-Myc, provide an effective approach to determine the functional significance of AGO mutations identified in human cancers. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. Queens Univ Belfast, Belfast City Hosp, Dept Oncol, Canc Res Ctr, Belfast BT9 7AB, Antrim, North Ireland. Queens Univ Belfast, Belfast City Hosp, Dept Med Genet, Belfast BT9 7AB, Antrim, North Ireland. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,CNY-7,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu FU NCI NIH HHS [CA84066]; PHS HHS [P01 95281] NR 19 TC 36 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2005 VL 98 IS 1 BP 124 EP 128 DI 10.1016/j.ygyno.2005.04.007 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 942LP UT WOS:000230284200020 PM 15913747 ER PT J AU Saxon, AJ Oreskovich, MR Brkanac, Z AF Saxon, AJ Oreskovich, MR Brkanac, Z TI Genetic determinants of addiction to opioids and cocaine SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE genomics; polymorphism; substance-related disorders ID SEROTONIN TRANSPORTER GENE; SUBSTANCE USE DISORDERS; DOPAMINE-RECEPTOR GENE; CENTRAL-NERVOUS-SYSTEM; NO ASSOCIATION; UDP-GLUCURONOSYLTRANSFERASES; MOLECULAR-BIOLOGY; DRUG-ADDICTION; FUNCTIONAL POLYMORPHISM; FAMILIAL TRANSMISSION AB Objective: The completion of the human genome sequence has spurred investigation of the genetic contribution to substance dependence. In this article some of the recent scientific evidence for genetic determinants of opioid and cocaine dependence is reviewed. Method: An electronic search of the medical literature was conducted to locate published studies relevant to the genetics of opioid and cocaine dependence. The collected information judged to be most pertinent is described and discussed. Results: Genetic epidemiologic studies support a high degree of heritable vulnerability for both opioid and cocaine dependence. Polymorphisms in the genes coding for dopamine receptors and transporter, opioid receptors, endogenous opioid peptides, cannabinoid receptors, and serotonin receptors and transporter all appear to be associated with the phenotypic expression of this vulnerability once opioids or cocaine are consumed. Conclusions: Despite this initial progress, identification of specific genes and quantification of associated risk for the expression of each gene remain to be elucidated. While alteration of an individual's genome to change the phenotype seems remote, future interventions for treatment of opioid and cocaine dependence may include precise medications targeted to block the effects of proteins that have been identified through genetic research. C1 Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98108 USA. Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Washington Phys Hlth Plan, Seattle, WA USA. RP Saxon, AJ (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, S-116 ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Andrew.Saxon@med.va.gov NR 114 TC 31 Z9 32 U1 5 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2005 VL 13 IS 4 BP 218 EP 232 DI 10.1080/10673220500243364 PG 15 WC Psychiatry SC Psychiatry GA 965RS UT WOS:000231968600003 PM 16126608 ER PT J AU Jones, DS Krotick, S Johnson, B Morrison, AP AF Jones, DS Krotick, S Johnson, B Morrison, AP TI Waiting for rescue: An attorney who will not advocate for himself SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID ADDICTION; CANNABIS; BRAIN C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Psychoanalyt Soc & Inst, Boston, MA USA. RP Jones, DS (reprint author), 77 Massachusetts Ave,E51-290, Cambridge, MA 02139 USA. EM dsjones@mit.edu NR 26 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2005 VL 13 IS 4 BP 244 EP 256 DI 10.1080/10673220500250989 PG 13 WC Psychiatry SC Psychiatry GA 965RS UT WOS:000231968600005 PM 16126610 ER PT J AU Ganly, I Patel, SG Singh, B Kraus, DH Bridger, PG Cantu, G Cheesman, A De Sa, G Donald, P Fliss, DM Gullane, P Janecka, I Kamata, SE Kowalski, LP Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP AF Ganly, I Patel, SG Singh, B Kraus, DH Bridger, PG Cantu, G Cheesman, A De Sa, G Donald, P Fliss, DM Gullane, P Janecka, I Kamata, SE Kowalski, LP Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP TI Craniofacial resection for malignant paranasal sinus tumors: Report of an International Collaborative study SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE paranasal sinus neoplasms; craniofacial resection ID ANTERIOR SKULL BASE; NASAL CAVITY; CANCER; CARCINOMA; SURVIVAL; SURGERY; EXPERIENCE; THERAPY AB Background. Malignant tumors of the superior sinonasal vault are rare, and, because of this and the varied histologic findings, most outcomes data reflect the experience of small patient cohorts. This International Collaborative study examines a large cohort of patients accumulated from multiple institutions experienced in craniofacial surgery, with the aim of reporting benchmark figures for outcomes and identifying patient-related and tumor-related predictors of prognosis after craniofacial resection (CFR). Methods. Three hundred thirty-four patients from 17 institutions were analyzed for outcome. Patients with esthesioneuroblastoma were excluded and are being reported separately. The median age was 57 years (range, 3-98 years). One hundred eighty-eight patients (56.3%) had had prior single-modality or combined treatment, which included surgery in 120 (36%), radiation in 79 (23.7%), and chemotherapy in 56 (16.8%). The most common histologic findings were adenocarcinoma in 107 (32%) and squamous cell carcinoma in 101 (30.2%). The margins of resection were close or microscopically positive in 95 (30%). Adjuvant radiotherapy was given in 161 (48.2%) and chemotherapy in 16 (4.8%). Statistical analyses for outcomes were performed in relation to patient characteristics, tumor characteristics, including histologic findings and extent of disease, surgical resection margins, prior radiation, and prior chemotherapy to determine predictive factors. Results. Postoperative mortality occurred in 15 patients (4.5%). Postoperative complications occurred in 110 patients (32.9%). The 5-year overall, disease-specific, and recurrence-free survival rates were 48.3%, 53.3%, and 45.8%, respectively. The status of surgical margins, histologic findings of the primary tumor, and intracranial extent were independent predictors of overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusions. CFR for malignant paranasal sinus tumors is a safe surgical treatment with an overall mortality of 4.5% and complication rate of 33%. The status of surgical margins, histologic findings of the primary tumor, and intracranial extent are independent predictors of outcome. (c) 2005 Wiley Periodicals, Inc. C1 Mem Sloan Kettering Canc Ctr, Head & Neck Serv, New York, NY 10021 USA. Prince Wales Hosp, Sydney, NSW, Australia. Ist Nazl Tumori, I-20133 Milan, Italy. Royal Natl Throat Nose & Ear Hosp, London WC1X 8DA, England. Ist Nacl Canc, Rio De Janeiro, Brazil. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Toronto Gen Hosp, Toronto, ON, Canada. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Canc Inst Hosp, Tokyo, Japan. Hosp Canc AC Camargo, Sao Paulo, Brazil. Univ Virginia, Hlth Syst, Charlottesville, VA USA. Hosp Clin Sao Paulo, Sao Paulo, Brazil. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Ctr Head & Neck Surg, Denver, CO USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Shah, JP (reprint author), Mem Sloan Kettering Canc Ctr, Head & Neck Serv, 1275 York Ave, New York, NY 10021 USA. EM shahj@mskcc.org RI Wei, William/C-4435-2009; Francisco, Suely/D-9065-2014; Kowalski, Luiz/D-1701-2012; OI Kowalski, Luiz/0000-0001-5865-9308; Ganly, Ian/0000-0001-7636-5426; wei, william/0000-0002-6281-7126; Shah, Jatin/0000-0002-6444-6592; Kowalski, Luiz Paulo/0000-0002-0481-156X NR 20 TC 110 Z9 113 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 2005 VL 27 IS 7 BP 575 EP 584 DI 10.1002/hed.20165 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 941VL UT WOS:000230242200004 PM 15825201 ER PT J AU Khan, AM Whiten, DM Nadol, JB Eddington, DK AF Khan, AM Whiten, DM Nadol, JB Eddington, DK TI Histopathology of human cochlear implants: Correlation of psychophysical and anatomical measures SO HEARING RESEARCH LA English DT Article DE cochlear implantation; spiral ganglion cells; psychophysics ID SENSORINEURAL HEARING-LOSS; SPIRAL GANGLION-CELLS; SPEECH-RECOGNITION; ELECTRODE DISCRIMINATION; TEMPORAL BONES; COST-UTILITY; PLACE-PITCH; PERCEPTION; PATIENT; RECONSTRUCTION AB The cadavaric temporal bones of five subjects who underwent cochlear implantation during life (2 Nucleus and 3 Ineraid) were analyzed using two-dimensional (2D) reconstruction of serial sections to determine the number of surviving spiral ganglion cells (SGCs) in the region of each electrode of the implanted arrays. The last psychophysical threshold and maximum-comfortable sensation level treasured for each electrode were compared to their respective SGC count to determine the across-electrode psychophysical variance accounted for by the SGC counts. Significant correlations between psychophysical measures and SGC counts were found in only two of the five subjects: one Nucleus implantee (e.g., r=-0.71; p < 0.001 for threshold vs. count) and one Ineraid implantee (e.g., r=-0.86; p < 0.05 for threshold vs. count). A three-dimensional (3D) model of the implanted cochlea was formulated using the temporal-bone anatomy of the Nucleus subject for whom the 2D analysis did not result in significant correlations between counts and psychophysical measures. Predictions of the threshold vs. electrode profile were closer to the measured profile for the 3D model than for the 2D analysis. These results lead us to hypothesize that 3D techniques will be required to asses the impact of peripheral anatomy on the benefit patients derive from cochlear implantation. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02369 USA. MIT, Elect Res Lab, Cambridge, MA 02369 USA. RP Eddington, DK (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, 243 Charles St, Boston, MA 02114 USA. EM dke@cirl.meei.harvard.edu NR 50 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2005 VL 205 IS 1-2 BP 83 EP 93 DI 10.1016/j.heares.2005.03.003 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 941UJ UT WOS:000230239400008 PM 15953517 ER PT J AU Cox, AL Mosbruger, T Lauer, GM Pardoll, D Thomas, DL Ray, SC AF Cox, AL Mosbruger, T Lauer, GM Pardoll, D Thomas, DL Ray, SC TI Comprehensive analyses of CD8+T cell responses during longitudinal study of acute human hepatitis C SO HEPATOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; INJECTION-DRUG USE; NON-B-HEPATITIS; VIRUS-INFECTION; IMMUNE-RESPONSES; PERIPHERAL-BLOOD; LONG-TERM; QUANTITATIVE-ANALYSIS; VIRAL CLEARANCE; DENDRITIC CELLS AB We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma-secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the. magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection. In conclusion, in most individuals, the CD8+ T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses. C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ray, SC (reprint author), Viral Hepatitis Ctr, 1503 E Jefferson St, Baltimore, MD 21231 USA. EM sray@jhmi.edu RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU NIAID NIH HHS [U19 AI040035, U19 AI040035-100003, U19 AI40035]; NIDA NIH HHS [K08 DA11880]; NIDDK NIH HHS [R01 DK057998, R01 DK057998-05, R01 DK57998] NR 55 TC 160 Z9 168 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2005 VL 42 IS 1 BP 104 EP 112 DI 10.1002/hep.20749 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 941BI UT WOS:000230189200015 PM 15962289 ER PT J AU Nakamura, M Masutomi, K Kyo, S Hashimoto, M Maida, Y Kanaya, T Tanaka, M Hahn, WC Inoue, M AF Nakamura, M Masutomi, K Kyo, S Hashimoto, M Maida, Y Kanaya, T Tanaka, M Hahn, WC Inoue, M TI Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy SO HUMAN GENE THERAPY LA English DT Article ID CATALYTIC SUBUNIT; DNA-REPAIR; LEUKEMIA-CELLS; IN-VIVO; TOPOISOMERASE; MECHANISMS; STABILITY; GENE AB Telomerase activation plays critical roles in tumor growth and progression in part through the maintenance of telomere structure. Indeed, the ubiquitous expression of telomerase in human cancers makes telomerase a promising target for cancer therapy. Genetic, pharmacologic, and antisense methods to inhibit telomerase have been described; however, in most cases, cancer cell death was observed only after many cell divisions. Here, using retroviral delivery of small interfering RNAs (siRNAs) specific for the human telomerase reverse transcriptase ( hTERT), we successfully inhibited telomerase activity in cervical cancer cell lines. Cells lacking hTERT expression exhibited significantly decreased telomerase activity and showed shortened telomeres and telomeric 3' overhangs with passage. These cells entered replicative senescence after a considerable number of cell divisions. Notably, the proliferative rate of these cells was significantly impaired, compared with control cells with telomerase activity, even in low-passage cells ( population doubling 5). Likewise, colony-forming ability and tumorigenicity in mice were attenuated in low-passage cells lacking hTERT. We further examined the effects of chemotherapy and ionizing radiation on cells in which hTERT expression was suppressed. Cells lacking hTERT showed a significantly increased sensitivity, compared with control cells, to ionizing radiation or chemotherapeutic agents that induce DNA double-strand breaks, such as topoisomerase inhibitors or bleomycin. These findings suggest that an siRNA-based strategy can be applied to the development of novel telomerase inhibitors, the antitumor effects of which may be enhanced in combination with ionizing radiation and chemotherapy. C1 Kanazawa Univ, Grad Sch, Dept Obstet & Gynecol, Kanazawa, Ishikawa 9208641, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kyo, S (reprint author), Kanazawa Univ, Grad Sch, Dept Obstet & Gynecol, 13-1,Takaramachi, Kanazawa, Ishikawa 9208641, Japan. EM satoruky@med.kanazawa-u.ac.jp FU NCI NIH HHS [K01 CA94223] NR 39 TC 55 Z9 70 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2005 VL 16 IS 7 BP 859 EP 868 DI 10.1089/hum.2005.16.859 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 945CF UT WOS:000230478300008 PM 16000067 ER PT J AU Yuan, CM Vergilio, JA Zhao, XF Smith, TK Harris, NL Bagg, A AF Yuan, CM Vergilio, JA Zhao, XF Smith, TK Harris, NL Bagg, A TI CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10(+) T cells by flow cytometry SO HUMAN PATHOLOGY LA English DT Article DE angioimmunoblastic; T cell; lymphoma; CD10; AITCL; flow cytometry ID CENTER B-CELLS; LYMPHOBLASTIC-LEUKEMIA ANTIGEN; HYPERPLASTIC GERMINAL-CENTERS; GENE REARRANGEMENTS; PROTEIN; IMMUNOGLOBULIN; PCR AB Angioimmunoblastic T-cell lymphoma (AITCL) is a histologically distinct and relatively common subtype of T-cell lymphoma. Although the putative normal cell counterpart is a mature CD4(+) T cell, the precise cell of origin remains elusive. We evaluated cases with a diagnosis of AITCL to determine the specificity and utility of CD10 coexpression, particularly by flow cytometry (FCM), in facilitating this diagnosis. Coexpression of BCL6 was also assessed. Eight AITCL cases were evaluated histologically, immunohistochemically, and by 4-color FCM. Four cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), were also analyzed. The lymphoma cells in all 8 AITCL cases were CD4(+), CD45RO(+) T cells, with classic extrafollicular meshworks of CD21/CD23/CD35(+) follicular dendritic cells. Furthermore, all cases of AITCL cases contained interfollicular CD10(+) cells by immunohistochemistry, and increased coexpression of CD 10 on T cells was also detected in 6 of 8 cases by FCM. CD 10 coexpression was not observed in all 4 PTCL-NOS cases. Although not specific for AITCL, increased numbers of BCL6(+) cells were seen in AITCL as compared with PTCL-NOS. Double immunohistochemistry performed on an AITCL case with high numbers of BCL6(+) cells highlighted coexpression of BCL6 and CD4 on the same cells. The finding suggests that AITCL may be a neoplasm of (possibly intrafollicular) CD 10(+), BCL6(+), and CD4(+) memory T cells. Although our series is small, our results suggest that CD10 coexpression may be a useful discriminant, particularly if the differential diagnosis is PTCL-NOS, and demonstrate that this can be determined by FCM. (C) 2005 Published by Elsevier Inc. C1 Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bagg, A (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM adambagg@mail.med.upenn.edu NR 28 TC 32 Z9 39 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 JUL PY 2005 VL 36 IS 7 BP 784 EP 791 DI 10.1016/j.humpath.2005.05.008 PG 8 WC Pathology SC Pathology GA 956NE UT WOS:000231305800013 PM 16084948 ER PT J AU Jacobs, RR Anderson, RR Chiou, A Esterowitz, L Izatt, JA Matthews, DL AF Jacobs, RR Anderson, RR Chiou, A Esterowitz, L Izatt, JA Matthews, DL TI Introduction to the issue on biophotonics SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 Lawrence Livermore Natl Lab, NSF, CBST, Livermore, CA 94551 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Natl Yang Ming Univ, Sch Med Technol & Engn, Taipei 112, Taiwan. Natl Sci Fdn, Arlington, VA 22230 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Univ Calif Davis, NSF, CBST, Sacramento, CA 95817 USA. RP Jacobs, RR (reprint author), Lawrence Livermore Natl Lab, NSF, CBST, Livermore, CA 94551 USA. NR 0 TC 1 Z9 1 U1 3 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 2005 VL 11 IS 4 BP 729 EP 729 DI 10.1109/JSTQE.2005.857675 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 990FL UT WOS:000233728500001 ER PT J AU Wang, G Jaszczak, RJ Basilion, JP AF Wang, G Jaszczak, RJ Basilion, JP TI Guest editorial toward molecular Imaging SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Editorial Material C1 Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. Duke Univ, Dept Radiol, Durham, NC 27708 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, G (reprint author), Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2005 VL 24 IS 7 BP 829 EP 831 DI 10.1109/TMI.2005.848987 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 941ML UT WOS:000230218800001 ER PT J AU Zacharakis, G Ripoll, J Weissleder, R Ntziachristos, V AF Zacharakis, G Ripoll, J Weissleder, R Ntziachristos, V TI Fluorescent protein tomography scanner for small animal imaging SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE diffusion theory; fluorescence tomography; visible light; whole-body imaging ID DIFFUSE OPTICAL TOMOGRAPHY; GENE-EXPRESSION; BODY; RECONSTRUCTION; ANGIOGENESIS; MICROSCOPY; BREAST; TUMORS; MEDIA; CELLS AB Microscopy of fluorescent proteins has enabled unprecedented insights into visualizing gene expression in living systems. Imaging deeper into animals, however, has been limited due to the lack of accurate imaging methods for the visible. We present a novel system designed to perform tomographic imaging of fluorescent proteins through whole animals. The tomographic method employed a multiangle, multiprojection illumination scheme, while detection was achieved using a highly sensitive charge-coupled device camera with appropriate filters. Light propagation was modeled using a modified solution to the diffusion equation to account for the high absorption and high scattering of tissue at the visible wavelengths. We show that the technique can quantitatively detect fluorescence with sub millimeter spatial resolution both in phantoms and in tissues. We conclude that the method could be applied in tomographic imaging of fluorescent proteins for in vivo targeting of different diseases and abnormalities. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, GR-71110 Iraklion, Greece. RP Zacharakis, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM zahari@iesl.forth.gr; jripoll@iesl.forth.gr; vasilis@helix.mgh.harvard.edu RI Zacharakis, Giannis/A-2544-2014; Ripoll, Jorge/J-8134-2012 OI Zacharakis, Giannis/0000-0002-6438-0773; Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33 CA 91807]; NIBIB NIH HHS [R01 EB 000750-1] NR 29 TC 70 Z9 71 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2005 VL 24 IS 7 BP 878 EP 885 DI 10.1109/TMI.2004.843254 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 941ML UT WOS:000230218800007 PM 16011317 ER PT J AU Marias, K Ripoll, J Meyer, H Ntziachristos, V Orphanoudakis, S AF Marias, K Ripoll, J Meyer, H Ntziachristos, V Orphanoudakis, S TI Image analysis for assessing molecular activity changes in time-dependent geometries SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE image registration; image sequence analysis; optical image processing ID THIN-PLATE SPLINES; MUTUAL-INFORMATION; REGISTRATION AB In vivo fluorescence molecular imaging and tomography has facilitated monitoring of genomics and proteomics over time and on the same animal. A highly important issue, however, has been the robust registration of animals imaged at different time points to obtain accurate description of activity and location. This paper presents a method for aligning temporal data of small animals based on surface anatomical features and improving the accuracy of monitoring fluorophore distribution. The method can account for differences in the positioning and compression of small animals and can be extended to three-dimensional as well as to other imaging modalities. C1 FORTH, ICS, GR-71110 Iraklion, Greece. Univ Oxford, Dept Engn Sci, Med Vision Lab, Oxford OX1 3PJ, England. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, GR-71110 Iraklion, Greece. Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Univ Crete, Dept Comp Sci, Iraklion, Greece. RP Marias, K (reprint author), FORTH, ICS, GR-71110 Iraklion, Greece. EM kmarias@ics.forth.gr; jripoll@iesi.forth.gr; heimeyer@iesl.forth.gr; vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33 CA 91807]; NIBIB NIH HHS [R01 EB000750-1] NR 16 TC 7 Z9 7 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2005 VL 24 IS 7 BP 894 EP 900 DI 10.1109/TMI.2005.848612 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 941ML UT WOS:000230218800009 PM 16011319 ER PT J AU Mylonakis, E Aballay, A AF Mylonakis, E Aballay, A TI Worms and flies as genetically tractable animal models to study host-pathogen interactions SO INFECTION AND IMMUNITY LA English DT Review ID DROSOPHILA IMMUNE-RESPONSE; PEPTIDOGLYCAN RECOGNITION PROTEIN; NEMATODE CAENORHABDITIS-ELEGANS; GENOME-WIDE ANALYSIS; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; SALMONELLA-TYPHIMURIUM; VIRULENCE FACTORS; C-ELEGANS; CRYPTOCOCCUS-NEOFORMANS C1 Duke Univ, Ctr Med, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Aballay, A (reprint author), Duke Univ, Ctr Med, Dept Mol Genet & Microbiol, Box 3580, Durham, NC 27710 USA. EM a.aballay@duke.edu FU NIGMS NIH HHS [R01 GM070977, R01GM070977] NR 86 TC 82 Z9 107 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 3833 EP 3841 DI 10.1128/IAI.73.7.3833-3841.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100002 PM 15972468 ER PT J AU Mylonakis, E Moreno, R El Khoury, JB Idnurm, A Heitman, J Calderwood, SB Ausubel, FM Diener, A AF Mylonakis, E Moreno, R El Khoury, JB Idnurm, A Heitman, J Calderwood, SB Ausubel, FM Diener, A TI Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID CANDIDA-ALBICANS MUTANTS; NITRIC-OXIDE SYNTHASE; PSEUDOMONAS-AERUGINOSA; IN-VIVO; CAENORHABDITIS-ELEGANS; PROTEUS-MIRABILIS; RANDOMIZED-TRIAL; IMMUNE-RESPONSE; AMPHOTERICIN-B; SEXUAL CYCLE AB Evaluation of Cryptococcus neoformans virulence in a number of nomnammalian hosts suggests that C neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax moth) caterpillar by C neoformans to develop an invertebrate host model system that can be used to study cryptococcal virulence, host immune responses to infection, and the effects of antifungal compounds. All varieties of C neoformans killed G. mellonella. After injection into the insect hemocoel, C neoformans proliferated and, despite successful phagocytosis by host hemocytes, killed caterpillars both at 37 degrees C and 30 degrees C. The rate and extent of killing depended on the cryptococcal strain and the number of fungal cells injected. The sequenced C. neoformans clinical strain H99 was the most virulent of the strains tested and killed caterpillars with inocula as low as 20 CFU/caterpillar. Several C. neoformans genes previously shown to be involved in mammalian virulence (CAP59, GPA1, X4S1, and PKA1) also played a role in G. mellonella killing. Combination antifungal therapy (amphotericin B plus flucytosine) administered before or after inoculation was more effective than monotherapy in prolonging survival and in decreasing the tissue burden of cryptococci in the hemocoel. The G. mellonella-C. neoformans pathogenicity model may be a substitute for mammalian models of infection with C. neoformans and may facilitate the in vivo study of fungal virulence and efficacy of antifungal therapies. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org RI Idnurm, Alexander/K-8558-2013 OI Idnurm, Alexander/0000-0001-5995-7040 NR 54 TC 192 Z9 200 U1 4 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 3842 EP 3850 DI 10.1128/IAI.73.7.3842-3850.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100003 PM 15972469 ER PT J AU Aberra, FN Lichtenstein, GR AF Aberra, FN Lichtenstein, GR TI Methods to avoid infections in patients with inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE inflammatory bowel disease; ulcerative colitis; Crohn's disease; anti-inflammatory medications; immunomodulators; infections; prevention ID SEVERE ULCERATIVE-COLITIS; ACTIVE CROHNS-DISEASE; LOW-DOSE METHOTREXATE; EARLY POSTOPERATIVE COMPLICATIONS; ISRAELI MULTICENTER TRIAL; POPULATION-BASED COHORT; OF-THE-LITERATURE; DOUBLE-BLIND; CYTOMEGALOVIRUS-INFECTION; RHEUMATOID-ARTHRITIS AB Infections have been reported in patients with inflammatory bowel disease (IBD), especially in association with anti-inflammatory and immunomodulatory medications used to treat IBD. Unfortunately, there is a dearth of information on infectious complication risk in patients with IBD. This review describes infectious complications reported in patients with IBD and provides a framework for future studies to assess potential risk factors and incidence for infection. Recommendations are also provided for prevention of infection. C1 Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Med, Div Gastroenterol, Philadelphia, PA USA. RP Aberra, FN (reprint author), Hosp Univ Penn, Div Gastroenterol, 3rd Floor Ravdin Bldg, Philadelphia, PA 19104 USA. EM Faten.aberra@uphs.upenn.edu NR 112 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2005 VL 11 IS 7 BP 685 EP 695 DI 10.1097/01.MIB.0000160742.91602.b7 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 944NL UT WOS:000230435600010 PM 15973124 ER PT J AU Chan, AT Tranah, GJ Giovannucci, EL Willett, WC Hunter, DJ Fuchs, CS AF Chan, AT Tranah, GJ Giovannucci, EL Willett, WC Hunter, DJ Fuchs, CS TI Prospective study of N-acetyltransferase-2 genotypes, meat intake, smoking and risk of colorectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE N-acetyltransferase-2; heterocyclic amines; meat; cigarette smoke; colorectal cancer; genotype; genetic polymorphisms ID HETEROCYCLIC AMINES; COLON-CANCER; CIGARETTE-SMOKING; RAPID N-ACETYLTRANSFERASE-2; GENETIC SUSCEPTIBILITY; MOLECULAR-GENETICS; POOLED ANALYSIS; BREAST-CANCER; RED MEAT; ACETYLTRANSFERASE AB Consumption of red meat has been associated with elevated risk of colorectal cancer; however, mechanisms underlying this relationship are not well established. N-acetyltransferase 2 (NAT2) appears to activate carcinogenic heterocyclic amines found in meat as well as cigarette smoke. Genetic variation in this enzyme, associated with rapid acetylation, may modulate the influence of meat intake on cancer risk. We examined the risk of incident colorectal cancer according to NAT2 genotypes, meat intake and smoking in a prospective, nested case-control study among 32,826 women enrolled in the Nurses' Health Study who provided prediagnostic blood specimens. We matched 183 women with colorectal cancer to 443 controls. Although acetylator genotype alone was not associated with the risk of colorectal cancer, women with rapid acetylator genotypes experienced a greater risk associated with intake of > 0.5 serving of beef, pork or lamb as a main dish per day compared to intake of less meat (multivariate OR = 3.01; 95% CI = 1.10-8.18). In contrast, among slow acetylators, intake of beef, pork or lamb was not associated with risk of colorectal cancer (multivariate OR = 0.87; 95% CI = 0.35-2.17). The interaction between acetylator genotype and meat intake approached statistical significance (P-interaction = 0.07). Moreover, compared to slow acetylators who smoked < 35 pack-years and ate < 0.5 serving/day of red meat, the OR for rapid acetylators who smoked > 35 pack-years and ate > 0.5 serving/clay was 17.6 (95% CI 2.0-158.3). These prospective data suggest that red meat may increase the risk of colorectal cancer, particularly among genetically susceptible individuals. The influence of NAT2 genotype on this association supports a role for heterocyclic amines in mediating the effect of red meat on colorectal carcinogenesis. © 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA 87969, CA 09001-27, CA 55075]; NHLBI NIH HHS [HL 34594] NR 40 TC 50 Z9 51 U1 1 U2 3 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 JUL 1 PY 2005 VL 115 IS 4 BP 648 EP 652 DI 10.1002/ijc.20890 PG 5 WC Oncology SC Oncology GA 925WA UT WOS:000229082800020 PM 15700302 ER PT J AU Becker, AE Thomas, JJ Franko, DL Herzog, DB AF Becker, AE Thomas, JJ Franko, DL Herzog, DB TI Disclosure patterns of eating and weight concerns to clinicians, educational professionals, family, and peers SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE disclosure; primary care; treatment seeking ID ANOREXIA-NERVOSA; DISORDERS; CARE; PHYSICIAN; BULIMIA; WOMEN AB Objective: The current study investigated disclosure of eating and weight concerns to professionals, peers, and family. Method: Responses to a telephone questionnaire probing disclosure patterns were analyzed in a sample of 216 adult subjects with eating or weight symptoms, concerns, or problems. Results: Nearly all of the sample (97.7%) had disclosed information about eating or weight symptoms or concerns to someone. Only 57% of the sample had disclosed this information to a health care professional. However, among subjects who had not otherwise volunteered information about their concerns, those who were queried were more likely than not to disclose them to health care professionals, counselors, and coaches. Disclosure to a health care professional or school counselor was associated with a higher likelihood of subsequent treatment seeking. Discussion: These data suggest that individuals with disordered eating may be quite amenable to disclosing symptoms in clinical settings. Asking about an eating disorder may enhance detection and facilitate treatment in clinical settings. (c) 2005 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Harvard Eating Disorders Ctr, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Harvard Eating Disorders Ctr, Dept Psychiat, 32 Fruit St,YAW 6900, Boston, MA 02114 USA. EM d.franko@neu.edu NR 21 TC 25 Z9 25 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2005 VL 38 IS 1 BP 18 EP 23 DI 10.1002/eat.20141 PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 941JV UT WOS:000230212000004 PM 15971235 ER PT J AU Yamagata, T Maki, K Mitani, K AF Yamagata, T Maki, K Mitani, K TI Runx1/UAML1 in normal and abnormal hematopoiesis SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Runx1/AML1; chromosomal translocation; point mutation; leukemia; transcription factor ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; AML1-ETO FUSION PROTEIN; NUCLEAR RECEPTOR COREPRESSOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELLS; MYELODYSPLASTIC SYNDROME; EMBRYONIC LETHALITY; POINT MUTATIONS; BINDING-PROTEIN AB Runx1/AML1 (also known as CBFA2 and PEBP2 alpha B) is a Runt family transcription factor critical for normal hematopoiesis. Runx1 forms a heterodimer with CBF beta and binds to the consensus PEBP2 sequence through the Runt domain. Runx1 enhances gene transcription by interacting with transcriptional coactivators such as p300 and CREB-binding protein. However, Runxl can also suppress gene transcription by interacting with transcriptional corepressors, including mSin3A, TLE (mammalian homolog of Groucho), and histone deacetylases. Runx1 not only is critical for definitive hematopoiesis in the fetus but also is required for normal megakaryocytic maturation and T-lymphocyte and B-lymphocyte development in adult mice. Runxl has been identified in leukemia-associated chromosomal translocations, including t(8;21) (Runx1-ETO/MTG8), t(16;21) (Runx1-MTG16), t(3;21) (Runx1-Evi1), t(12;21) (TEL-Runx1), and t(X;21) (Runx1-Fog2). The molecular mechanism of leukemogenesis by these fusion proteins is discussed. Various mutant mice expressing these fusion proteins have been created. However, expression of the fusion protein is not sufficient by itself to cause leukemia and likely requires additional events for leukemogenesis. Point mutations in a Runx1 allele cause haploinsufficiency and a biallelic null for Runx1, which are associated with familial platelet disorder with a propensity for acute myeloid leukemia (FPD/AML) and AML-MO, respectively. Thus, the correct protein structure and the precise dosage of Runx1 are essential for the maintenance of normal hematopoiesis. C1 Dokkyo Univ, Sch Med, Dept Hematol, Mibu, Tochigi 3210293, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. RP Mitani, K (reprint author), Dokkyo Univ, Sch Med, Dept Hematol, 880 Kitakobayashi, Mibu, Tochigi 3210293, Japan. EM kinukom-tky@umin.ac.jp NR 80 TC 43 Z9 45 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2005 VL 82 IS 1 BP 1 EP 8 DI 10.1532/IJH97.05075 PG 8 WC Hematology SC Hematology GA 952AJ UT WOS:000230973200001 PM 16105753 ER PT J AU Liu, Q Hamblin, MR AF Liu, Q Hamblin, MR TI Macrophage-targeted photodynamic therapy: Scavenger receptor expression and activation state SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Article DE photodynamic therapy; macrophages; scavenger receptor; photosensitizer conjugate; interferon gamma; lipopolysaccharide; tumor necrosis factor alpha ID TUMOR-ASSOCIATED MACROPHAGES; HUMAN MONOCYTE-MACROPHAGES; LOW-DENSITY-LIPOPROTEIN; TOLL-LIKE RECEPTORS; MEDIATED RECOGNITION; HOST-DEFENSE; ATHEROSCLEROSIS; FAMILY; CD36; IDENTIFICATION AB Macrophage-targeted photodynamic therapy (PDT) may have applications in the selective killing of cells involved in atherosclerosis, inflammation and tumor. We have previously shown that a conjugate between the photosensitizer chlorin(e6) (ce6) and maleylated bovine serum albumin (BSA-mal) gives highly selective targeting to macrophages. In this report we examine the effect of macrophage activation and scavenger receptor class A (SRA) expression on this targeting in two murine macrophage tumor cell lines (RAW264.7 and P388D1) and a control murine mammary sarcoma cell line (EMT-6). Cells were pretreated with interferon gamma (IFN gamma) and/or lipopolysaccharide (LPS) followed byBSA-ce6-mal addition, and SRA expression, tumor necrosis factor alpha (TNF alpha) release, conjugate uptake and PDT killing were measured. Both macrophage cell lines expressed SRA and took up conjugate specifically in an SRA-dependent manner, but differences were observed in their response to activation. RAW264.7 expressed increasingly more SRA and took up increasingly more BSA-ce6-mal in response to IFN gamma, LPS, and IFN gamma+LPS, respectively. The PDT killing did not follow the same pattern as the uptake of the photosensitizer. The increase in uptake in the IFN gamma treated cells did not lead to an increase in PDT killing, while stimulation with LPS or IFN gamma+LPS resulted in a significant protection against PDT, despite a significant increase in photosensitizer uptake. P388D1 was responsive to neither IFN gamma, nor to LPS, or to IFN gamma+LPS with respect to SRA expression, conjugate uptake, and PDT killing. These data may have implications for the use of PDT to target physiologically undesirable macrophage subtypes implicated in disease, and on how manipulation of the activation status of the macrophage will influence the PDT effect. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR14,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA083882-01A2, R01 CA083882-02, R01 CA083882-03, R01-CA/AI838801] NR 44 TC 24 Z9 25 U1 0 U2 2 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD JUL-SEP PY 2005 VL 18 IS 3 BP 391 EP 402 PG 12 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 975IV UT WOS:000232655100001 PM 16164823 ER PT J AU Bedwell, JS Horner, MD Yamanaka, K Li, XB Myrick, H Nahas, Z George, MS AF Bedwell, JS Horner, MD Yamanaka, K Li, XB Myrick, H Nahas, Z George, MS TI Functional neuroanatomy of subcomponent cognitive processes involved in verbal working memory SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE functional magnetic resonance imaging; healthy adults; neuroimaging; Sternberg working memory task; subcomponent cognitive processes; verbal working memory ID AGE-RELATED-CHANGES; PREFRONTAL CORTEX; NEURAL MECHANISMS; BRAIN-REGIONS; REACTION-TIME; FMRI; MAINTENANCE; ROLES; MANIPULATION; PERFORMANCE AB bRecent research has used functional magnetic resonance imaging (fMRI) to examine brain regions related to specific subcomponent cognitive processes of verbal working memory. which include initial encoding of material, maintenance of the information over a brief delay interval, and later retrieval of the information. The present study examined each of these subcomponents in 14 healthy adults using a Sternberg verbal working memory task and fMRI. Group proanalysis revealed several brain regions active during all subcomponent processes, which included dorsolateral and ventrolateral prefrontal, parietal, hippocampal, and premotor cortex. Several other brain regions showed activation limited to specific subcomponent processes. C1 Univ Cent Florida, Dept Psychol, Orlando, FL 32816 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. Med Univ S Carolina, CAIR, Dept Psychiat, Charleston, SC 29425 USA. RP Bedwell, JS (reprint author), Univ Cent Florida, Dept Psychol, Orlando, FL 32816 USA. EM jbedwell@mail.ucf.edu FU NIA NIH HHS [R01-AG40956] NR 36 TC 18 Z9 19 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PD JUL PY 2005 VL 115 IS 7 BP 1017 EP 1032 DI 10.1080/00207450590901530 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 941EJ UT WOS:000230197800008 PM 16051547 ER PT J AU Wilson, LD Haffty, BG Harris, JR AF Wilson, LD Haffty, BG Harris, JR TI Radiation oncology, resident research, and the American Board of radiology Holman Pathway SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wilson, LD (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, HRT 136,333 Cedar St, New Haven, CT 06510 USA. EM lynn.wilson@yale.edu NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2005 VL 62 IS 3 BP 623 EP 625 DI 10.1016/j.ijrobp.2005.03.015 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 935FY UT WOS:000229766300001 PM 15936535 ER PT J AU Zietman, AL Christodouleas, JP Shipley, WU AF Zietman, AL Christodouleas, JP Shipley, WU TI PSA bounces after neoadjuvant androgen deprivation and external beam radiation: Impact on definitions of failure SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE androgen deprivation; prostate cancer; PSA; radiation ID LOCALIZED PROSTATE-CANCER; SUPERIOR PREDICTIVE POWER; BIOCHEMICAL FAILURE; ANTIGEN BOUNCE; FOLLOW-UP; RELAPSE DEFINITIONS; SEED IMPLANTATION; BRACHYTHERAPY; TESTOSTERONE; RADIOTHERAPY AB Purpose: To determine the characteristics of prostate specific antigen (PSA) bounces after external beam radiation therapy (EBRT) with neoadjuvant androgen deprivation and their impact on definitions of biochemical failure. Methods and Materials: Characteristics of bounce were calculated for all patients treated by EBRT with neoadjuvant androgen deprivation at our institution between 1992 and 1998 (preexclusion analysis). Calculations were repeated for the subgroup that satisfied additional inclusion/exclusion criteria (postexclusion analysis). The percentage of bounces scoring as false positives according to the ASTRO definition of biochemical failure was compared with those for three alternative definitions (Vancouver, Nadir-plus-two, and Nadir-plus-three) using McNemar's tests. Results: Thirty-nine percent (preexclusion cohort) and 56% (postexclusion cohort) of patients demonstrated a PSA bounce. Twenty percent (preexclusion analysis) and 25% (postexclusion analysis) of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition scored the smallest percentage of bounces as failure, but the difference between this definition and the ASTRO definition reached statistical significance in neither preexclusion nor postexclusion analyses (P >= 0.070). Conclusions: A substantial proportion of patients treated by EBRT with neoadjuvant deprivation experienced a PSA bounce. A large percentage of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition is less vulnerable to this bias. (c) 2005 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM azietman@partners.org NR 25 TC 32 Z9 32 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 JUL 1 PY 2005 VL 62 IS 3 BP 714 EP 718 DI 10.1016/j.ijrobp.2004.11.020 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 935FY UT WOS:000229766300016 PM 15936550 ER PT J AU Downes, J Sutcliffe, I Tanner, ACR Wade, WG AF Downes, J Sutcliffe, I Tanner, ACR Wade, WG TI Prevotella marshii sp nov and Prevotella baroniae sp nov., isolated from the human oral cavity SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID GENUS AB Eleven strains of anaerobic Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise two homogeneous groups, designated E2 and E4. 16S rRNA gene sequence analysis revealed that members of both groups belonged to the genus Prevotella but were distinct from any species with validly published names. This distinction was confirmed by DNA-DNA hybridization and phenotypic tests. Two novel species are therefore proposed: Prevotella marshii sp. nov. (group E2) and Prevotella baroniae (group E4). Both species are saccharolytic; the end-products of fermentation for P. marshii are acetic, propionic and succinic acids, while P. baroniae produces acetic and succinic acids with minor amounts of isovaleric and isobutyric acids. The G+C content of the DNA of the type strain of Prevotella marshii is 51 mol% and that of Prevotella baroniae is 52 mol%. The type strain for P. marshii is E9.34(T) (=DSM 16973(T)=CCUG 50419(T)) and that for P. baroniae is E9.33(T) (=DSM 16972(T)=CCUG 50418(T)). C1 Kings Coll London, Inst Dent, Infect Res Grp, London SE1 9RT, England. Northumbria Univ, Sch Appl Sci, Div Biomed Sci, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Wade, WG (reprint author), Kings Coll London, Inst Dent, Infect Res Grp, London SE1 9RT, England. EM william.wade@kcl.ac.uk RI Sutcliffe, Iain/A-5354-2009; OI Sutcliffe, Iain/0000-0002-9036-2683; Wade, William/0000-0003-2685-826X FU NIDCR NIH HHS [DE 09513] NR 21 TC 35 Z9 36 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUL PY 2005 VL 55 BP 1551 EP 1555 DI 10.1099/ijs.0.63634-0 PN 4 PG 5 WC Microbiology SC Microbiology GA 949ZU UT WOS:000230828200024 PM 16014480 ER PT J AU Gregory, MS Koh, S Huang, E Saff, RR Marshak-Rothstein, A Mukai, S Ksander, BR AF Gregory, MS Koh, S Huang, E Saff, RR Marshak-Rothstein, A Mukai, S Ksander, BR TI A novel treatment for ocular tumors using membrane FasL vesicles to activate innate immunity and terminate immune privilege SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MOUSE PLEURAL CAVITY; M-BOVIS BCG; CANCER-IMMUNOTHERAPY; CONCOMITANT IMMUNITY; INTRAOCULAR TUMORS; AQUEOUS-HUMOR; CELL-ACTIVITY; IN-VIVO; LIGAND; APOPTOSIS AB PURPOSE. Ocular immune privilege promotes tumor growth by hindering the development of innate and adaptive immunity. A prior study showed that ocular tumors expressing the membrane-only form of Fas ligand (FasL) terminate immune privilege, induce vigorous inflammation, undergo rejection, and induce systemic protective immunity. In these previous experiments the tumor cells used were genetically engineered to express membrane FasL. As an initial step toward developing an immunotherapy for intraocular tumors, the present study was conducted to examine whether injection of microvesicles expressing membrane FasL into ocular tumors (that are FasL negative) would have a similar effect. METHODS. Microvesicles expressing either no FasL or membrane-only Fas ligand were coinjected with L5178Y-R lymphoma cells into the anterior chambers (AC) of DBA/2 mice. RESULTS. Tumor cells coinjected with control vesicles grew progressively in the AC, and all mice died of metastatic disease by day 15. By contrast, a single injection of membrane FasL vesicles induced a potent inflammatory response characterized by GR1(+) neutrophils and F4/80(+) macrophages and significantly improved survival from 0% in untreated mice to 58% in mFasL-treated mice. Among the surviving mice, the ocular tumor was eliminated in 55%, and the mice exhibited systemic protection from a second tumor challenge. In the remaining 45%, the ocular tumor was not eliminated, but the mice were protected from liver metastases. CONCLUSIONS. Bioactive membrane FasL microvesicles coinjected with tumor cells induce a potent inflammatory response that terminates immune privilege, eliminates ocular tumors, and prevents metastatic disease. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Ksander, BR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM ksander@vision.eri.harvard.edu FU NCI NIH HHS [CA-90691]; NEI NIH HHS [R01-EY08122, F32-EY13664] NR 41 TC 5 Z9 6 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2005 VL 46 IS 7 BP 2495 EP 2502 DI 10.1167/iovs-05-0048 PG 8 WC Ophthalmology SC Ophthalmology GA 939ZK UT WOS:000230112800037 PM 15980241 ER PT J AU Eller, LS Corless, I Bunch, EH Kemppainen, J Holzemer, W Nokes, K Portillo, C Nicholas, P AF Eller, LS Corless, I Bunch, EH Kemppainen, J Holzemer, W Nokes, K Portillo, C Nicholas, P TI Self-care strategies for depressive symptoms in people with HIV disease SO JOURNAL OF ADVANCED NURSING LA English DT Article DE critical incident technique; depression; HIV/AIDS; nursing; self management; self-care ID CRITICAL INCIDENT TECHNIQUE; SOCIAL SUPPORT; SEROPOSITIVE WOMEN; ALTERNATIVE THERAPIES; POSITIVE PATIENTS; INFECTED PATIENTS; MAJOR DEPRESSION; HOMOSEXUAL-MEN; GAY MEN; ADHERENCE AB Aim. This paper reports a study with people living with HIV to examine the experience of depressive symptoms, self-care symptom management strategies, symptom outcomes in response to those strategies, and sources from which the strategies were learned. Background. Depressive symptoms are common, under-diagnosed and under-treated in people living with HIV. These symptoms have been associated with lower medication adherence, risky behaviours and poorer health outcomes. Methods. The study was based on the model of symptom management developed by the University of California San Francisco School of Nursing Symptom Management Faculty. Thirty-four HIV+ men and women from a larger study of symptom self-care strategies (n = 422) reported experiencing depressive symptoms. Data were collected from this subset on the Web, by mail and in-person using the critical incident technique. Results. Depressive symptoms were described using 80 words and phrases clustered into eight categories: futility, sadness, loneliness/isolation, fatigue, fear/worry, lack of motivation, suicidal thoughts and other. A total of 111 self-care strategies were coded into six categories: practising complementary/alternative therapies, talking to others, using distraction techniques, using antidepressants, engaging in physical activity, and using denial/avoidant coping. Sources of information for strategies used were trial and error (31%), healthcare providers (28%), family and friends (20%), classes/reading (8%), clergy (8%), support groups (4%) and other (3%). Overall, 92% of the self-care strategies used were reported as helpful, 4% were sometimes helpful and 4% were not helpful. Conclusions. People living with HIV use numerous effective self-care strategies to manage depressive symptoms. Further study is needed to validate the use of these strategies across populations, to standardize dose, duration and frequency, and to measure their effectiveness. C1 Rutgers State Univ, Coll Nursing, Newark, NJ 07102 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Univ Oslo, Inst Nursing Sci, Oslo, Norway. Univ N Carolina, Sch Nursing, Wilmington, NC 28401 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. CUNY Hunter Coll, Hunter Bellevue Sch Nursing, New York, NY 10021 USA. RP Eller, LS (reprint author), Rutgers State Univ, Coll Nursing, 180 Univ Ave, Newark, NJ 07102 USA. EM eller@nightingale.rutgers.edu OI Corless, Inge/0000-0003-0438-2037 NR 56 TC 32 Z9 35 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD JUL PY 2005 VL 51 IS 2 BP 119 EP 130 DI 10.1111/j.1365-2648.2005.03474.x PG 12 WC Nursing SC Nursing GA 937GU UT WOS:000229913400003 PM 15963183 ER PT J AU Rush, AJ Zimmerman, M Wisniewski, SR Fava, M Hollon, SD Warden, D Biggs, MM Shores-Wilson, K Shelton, RC Luther, JF Thomas, B Trivedi, MH AF Rush, AJ Zimmerman, M Wisniewski, SR Fava, M Hollon, SD Warden, D Biggs, MM Shores-Wilson, K Shelton, RC Luther, JF Thomas, B Trivedi, MH TI Comorbid psychiatric disorders in depressed outpatients: Demographic and clinical features SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depression; symptoms; comorbid conditions; anxiety disorders; course of illness; morbidity; quality of life ID DIAGNOSTIC SCREENING QUESTIONNAIRE; NEUROPSYCHIATRIC INTERVIEW MINI; SEQUENCED TREATMENT ALTERNATIVES; PLACEBO-CONTROLLED TRIAL; ILLNESS RATING-SCALE; AXIS-I DISORDERS; STAR-ASTERISK-D; REPORT QIDS-SR; MAJOR DEPRESSION; DSM-III AB Background: This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). Methods: Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of I I different concurrent DSM-IV Axis I disorders. Results: Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for postraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. Limitations: Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. Conclusions: Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37240 USA. Birmingham VA Med Ctr, Community Resource Serv, Birmingham, AL USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01-MH-90003] NR 57 TC 147 Z9 156 U1 19 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2005 VL 87 IS 1 BP 43 EP 55 DI 10.1016/j.jad.2005.03.005 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 946YS UT WOS:000230609800006 PM 15894381 ER PT J AU Simon, NM Otto, MW Fischmann, D Racette, S Nierenberg, AA Pollack, MH Smoller, JW AF Simon, NM Otto, MW Fischmann, D Racette, S Nierenberg, AA Pollack, MH Smoller, JW TI Panic disorder and bipolar disorder: Anxiety sensitivity as a potential mediator of panic during manic states SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE panic; bipolar; anxiety sensitivity; manic; depression ID I DISORDER; MAJOR DEPRESSION; ATTACKS; EPIDEMIOLOGY; COMORBIDITY; SYMPTOMS; ILLNESS AB Background: Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. Methods: We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder (n = 110) or major depressive disorder (n = 92). Results: Current mood state was significantly associated with ASI score (Chi-square-21.2, df=4, p=0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores (p < 0.04). Current mixed state tended toward a similar association (p < 0.10). Limitations: Conclusions are limited by the study's cross-sectional nature and relatively small sample size. Conclusions: These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org FU NIMH NIH HHS [MH01831-0, MH01770] NR 25 TC 20 Z9 20 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2005 VL 87 IS 1 BP 101 EP 105 DI 10.1016/j.jad.2005.02.004 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 946YS UT WOS:000230609800012 PM 15894380 ER PT J AU Jessen, N Goodyear, LJ AF Jessen, N Goodyear, LJ TI Contraction signaling to glucose transport in skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE insulin receptor substrate-1; phosphatidylinositol 3-kinase; Type 2 diabetes ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; GAMMA-SUBUNIT ISOFORMS; NITRIC-OXIDE; GLUT4 TRANSLOCATION; IN-VITRO; YEAST SNF1; INSULIN SENSITIVITY; EXERCISE INTENSITY; DIABETES-MELLITUS AB Contracting skeletal muscles acutely increases glucose transport in both healthy individuals and in people with Type 2 diabetes, and regular physical exercise is a cornerstone in the treatment of the disease. Glucose transport in skeletal muscle is dependent on the translocation of GLUT4 glucose transporters to the cell surface. It has long been believed that there are two major signaling mechanisms leading to GLUT4 translocation. One mechanism is insulin-activated signaling through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The other is an insulin-independent signaling mechanism that is activated by contractions, but the mediators of this signal are still unknown. Accumulating evidence suggests that the energy-sensing enzyme AMP-activated protein kinase plays an important role in contraction-stimulated glucose transport. However, more recent studies in transgenic and knockout animals show that AMP-activated protein kinase is not the sole mediator of the signal to GLUT4 translocation and suggest that there may be redundant signaling pathways leading to contraction-stimulated glucose transport. The search for other possible signal intermediates is ongoing, and calcium, nitric oxide, bradykinin, and the Akt substrate AS160 have been suggested as possible candidates. Further research is needed because full elucidation of an insulin-independent signal leading to glucose transport would be a promising pharmacological target for the treatment of Type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Aarhus, Med Res Lab, Aarhus, Denmark. Univ Aarhus, Dept Clin Pharmacol, Aarhus, Denmark. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; OI Jessen, Niels/0000-0001-5613-7274 FU NIAMS NIH HHS [AR-42238, AR-45670] NR 123 TC 146 Z9 160 U1 2 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2005 VL 99 IS 1 BP 330 EP 337 DI 10.1152/japplphysiol.00175.2005 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 943WM UT WOS:000230385800044 PM 16036906 ER PT J AU Wang, ZY Wen, XH Ablonczy, Z Crouch, RK Makino, CL Lem, J AF Wang, ZY Wen, XH Ablonczy, Z Crouch, RK Makino, CL Lem, J TI Enhanced shutoff of phototransduction in transgenic mice expressing palmitoylation-deficient rhodopsin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN BETA-2-ADRENERGIC RECEPTOR; MASS-SPECTROMETRIC ANALYSIS; DEPENDENT PROTEIN-KINASE; IN-VIVO; BOVINE RHODOPSIN; BETA(2)-ADRENERGIC RECEPTOR; MULTIPLE PHOSPHORYLATION; CYSTEINE RESIDUES; ROD; OPSIN AB Palmitoylation is a reversible, post- translational modification observed in a number of G- protein- coupled receptors. To gain a better understanding of its role in visual transduction, we produced transgenic knock- in mice that expressed a palmitoylation- deficient rhodopsin (Palm (-/-)). The mutant rhodopsin was expressed at wild- type levels and showed normal cellular localization to rod outer segments, indicating that neither rhodopsin stability nor its intracellular trafficking were compromised. But Palm (-/-) rods had briefer flash responses and reduced sensitivity to flashes and to steps of light. Upon exposure to light, rhodopsin became phosphorylated at a faster rate in mutant than in wild- type retinas. Since quench of rhodopsin begins with its phosphorylation, these results suggest that palmitoylation may modulate rod photoreceptor sensitivity by permitting rhodopsin to remain active for a longer period. C1 Tufts Univ, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Tufts Univ, Sch Med, Tufts Ctr Vis Res, Dept Ophthalmol,Program Genet, Boston, MA 02111 USA. RP Lem, J (reprint author), Tufts Univ, New England Med Ctr, Mol Cardiol Res Inst, 750 Washington St,Box 5045, Boston, MA 02111 USA. EM Jlem@Tufts-NEMC.org OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [R24 EY014799, P30 EY013078, EY11358, EY014799, R01 EY004939, EY04939, EY12008, EY13078, F2EY13912A, F32 EY013912, P30 EY014104, P30 EY14104, R01 EY011358, R01 EY012008-04, R29 EY011358, R01 EY012008, R01 EY012008-05] NR 51 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 24293 EP 24300 DI 10.1074/jbc.M502588200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000001 PM 15851469 ER PT J AU Yu, PB Beppu, H Kawai, N Li, E Bloch, KD AF Yu, PB Beppu, H Kawai, N Li, E Bloch, KD TI Bone morphogenetic protein (BMP) type II receptor deletion reveals BMP ligand-specific gain of signaling in pulmonary artery smooth muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOGENIC PROTEIN-1; ACTIVIN RECEPTOR; FUNCTIONAL-ANALYSIS; BETA FAMILY; STEM-CELLS; IN-VIVO; HYPERTENSION; EXPRESSION; ACTIVATION; GENE AB Bone morphogenetic protein (BMP) ligands signal by binding the BMP type II receptor (BMPR2) or the activin type II receptors (ActRIIa and ActRIIb) in conjunction with type I receptors to activate SMADs 1, 5, and 8, as well as members of the mitogen- activated protein kinase family. Loss-of-function mutations in Bmpr2 have been implicated in tumorigenesis and in the etiology of primary pulmonary hypertension. Because several different type II receptors are known to recognize BMP ligands, the specific contribution of BMPR2 to BMP signaling is not defined. Here we report that the ablation of Bmpr2 in pulmonary artery smooth muscle cells, using an ex vivo conditional knock-out (Cre-lox) approach, as well as small interfering RNA specific for Bmpr2, does not abolish BMP signaling. Disruption of Bmpr2 leads to diminished signaling by BMP2 and BMP4 and augmented signaling by BMP6 and BMP7. Using small interfering RNAs to inhibit the expression of other BMP receptors, we found that wild-type cells transduce BMP signals via BMPR2, whereas BMPR2-deficient cells transduce BMP signals via ActRIIa in conjunction with a set of type I receptors distinct from those utilized by BMPR2. These findings suggest that disruption of Bmpr2 leads to the net gain of signaling by some, but not all, BMP ligands via the activation of ActRIIa. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Yu, PB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Navy Yard,149 13th St,4100A, Charlestown, MA 02129 USA. EM pbyu@partners.org OI Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [HL074352, K08 HL079943, K08 HL079943-01A1, T32-HL007208] NR 57 TC 120 Z9 126 U1 0 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 JUL 1 PY 2005 VL 280 IS 26 BP 24443 EP 24450 DI 10.1074/jbc.M502825200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000020 PM 15883158 ER PT J AU Williams, TM Hassan, GS Li, JW Cohen, AW Medina, F Frank, PG Pestell, RG Di Vizio, D Loda, M Lisanti, MP AF Williams, TM Hassan, GS Li, JW Cohen, AW Medina, F Frank, PG Pestell, RG Di Vizio, D Loda, M Lisanti, MP TI Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer - Genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONCOGENICALLY TRANSFORMED-CELLS; ANCHORAGE-INDEPENDENT GROWTH; BREAST-CANCER; TRANSGENIC MOUSE; EXPRESSION; CARCINOMA; METASTASIS; DIFFERENTIATION; ADENOCARCINOMA; OVEREXPRESSION AB Caveolin-1 (Cav-1) is the primary structural component of caveolae and is implicated in the processes of vesicular transport, cholesterol balance, transformation, and tumorigenesis. Despite an abundance of data suggesting that Cav-1 has transformation suppressor properties both in vitro and in vivo, Cav-1 is expressed at increased levels in human prostate cancer. To investigate the role of Cav-1 in prostate cancer onset and progression, we interbred Cav-1(-/-) null mice with a TRAMP (transgenic adenocarcinoma of mouse prostate) model that spontaneously develops advanced prostate cancer and metastatic disease. We found that, although the loss of Cav-1 did not affect the appearance of minimally invasive prostate cancer, its absence significantly impeded progression to highly invasive and metastatic disease. Inactivation of one (+/-) or both (-/-) alleles of Cav-1 resulted in significant reductions in prostate tumor burden, as well as decreases in regional lymph node metastases. Moreover, further examination revealed decreased metastasis to distant organs, such as the lungs, in TRAMP/Cav-1(-/-) mice. Utilizing prostate carcinoma cell lines (C1, C2, and C3) derived from TRAMP tumors, we also showed a positive correlation between Cav-1 expression and the ability of these cells to form tumors in vivo. Furthermore, down-regulation of Cav-1 expression in these cells, using a small interfering RNA approach, significantly reduced their tumorigenic and metastatic potential. Mechanistically, we showed that loss or down-regulation of Cav-1 expression results in increased apoptosis, with increased prostate apoptosis response factor-4 and PTEN levels in Cav-1(-/-) null prostate tumors. Our current findings provide the first in vivo molecular genetic evidence that Cav-1 does indeed function as a tumor promoter during prostate carcinogenesis, rather than as a tumor suppressor. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Urol, Bronx, NY 10461 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lisanti, MP (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM lisanti@aecom.yu.edu RI Lisanti, Michael/C-6866-2013; Williams, Terence/I-9614-2014; Frank, Philippe/A-3463-2011 OI Frank, Philippe/0000-0003-4857-5279 FU NIDDK NIH HHS [T32-DK07513] NR 34 TC 126 Z9 129 U1 3 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 25134 EP 25145 DI 10.1074/jbc.M501186200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000098 PM 15802273 ER PT J AU Graves, EE Yessayan, D Turner, G Weissleder, R Ntziachristos, V AF Graves, EE Yessayan, D Turner, G Weissleder, R Ntziachristos, V TI Validation of in vivo fluorochrome concentrations measured using fluorescence molecular tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence molecular tomography; fluorescent probes; diffuse optical tomography; molecular imaging ID DOMAIN PHOTON MIGRATION; CONTRAST AGENTS; TURBID MEDIA; IMAGE-RECONSTRUCTION; DIFFUSION TOMOGRAPHY; OPTICAL TOMOGRAPHY; RADIATIVE-TRANSFER; HUMAN SKIN; TUMORS; MICROSCOPY AB Fluorescence molecular tomography (FMT) has emerged as a means of quantitatively imaging fluorescent molecular probes in three dimensions in living systems. To assess the accuracy of FMT in vivo, translucent plastic tubes containing a turbid solution with a known concentration of Cy 5.5 fluorescent dye are constructed and implanted subcutaneously in nude mice, simulating the presence of a tumor accumulating a fluorescent molecular reporter. Comparisons between measurements of fluorescent tubes made before and after implantation demonstrate that the accuracy of FMT reported for homogeneous phantoms extends to the in vivo situation. The sensitivity of FMT to background fluorescence is tested by imaging fluorescent tubes in mice injected with Cy 5.5-labeled Annexin V. For small tube fluorochrome concentrations, the presence of background fluorescence results in increases in the reconstructed concentration. This phenomenon is counteracted by applying a simple subtraction correction to the measured fluorescence data. The effects of varying tumor photon absorption are simulated by imaging fluorescent tubes with varying ink concentrations, and are found to be minor. These findings demonstrate the in vivo quantitative accuracy of fluorescence tomography, and encourage further development of this imaging modality as well as application of FMT in molecular imaging studies using fluorescent reporters. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Charlestown, MA 02129 USA. RP Graves, EE (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, 875 Blake Wilbur Dr,CC-G202, Stanford, CA 94305 USA. EM egraves@stanford.edu; vasilis@helix.mgh.harvard.edu FU NCI NIH HHS [R21 CA 91807, P50 CA 86355, R24 CA 92782, T32 CA 79443]; NIBIB NIH HHS [R01 EB 000750-1] NR 45 TC 31 Z9 34 U1 0 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2005 VL 10 IS 4 AR 044019 DI 10.1117/1.1993427 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 977JJ UT WOS:000232799200028 PM 16178652 ER PT J AU Wood, KB Khanna, G Vaccaro, AR Arnold, PM Harris, MB Mehbod, AA AF Wood, KB Khanna, G Vaccaro, AR Arnold, PM Harris, MB Mehbod, AA TI Assessment of two thoracolumbarfracture classification systems as used by multiple surgeons SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FRACTURES; INJURIES; SPINE AB Background: The reproducibility and repeatability of modern systems for classification of thoracolumbar injuries have not been sufficiently studied. We assessed the interobserver and intraobserver reproducibility of the AO (Arbeitsgemeinschaft fur Osteosynthesefragen) classification and compared it with that of the Denis classification. Our purpose was to determine whether the newer, AO system had better reproducibility than the older, Denis classification. Methods: Anteroposterior and lateral radiographs and computerized tomography scans (axial images and sagittal reconstructions) of thirty-one acute traumatic fractures of the thoracolumbar spine were presented to nineteen observers, all trained spine surgeons, who classified the fractures according to both the AO and the Denis classification systems. Three months later, the images of the thirty-one fractures were scrambled into a different order, and the observers repeated the classification. The Cohen kappa (kappa) test was used to determine interobserver and intraobserver agreement, which was measured with regard to the three basic classifications in the AO system (types A, B, and C) as well as the nine subtypes of that system. We also measured the agreement with regard to the four basic types in the Denis classification (compression, burst, seat-belt, and fracture-dislocation) and with regard to the sixteen subtypes of that system. Results: The AO classification was fairly reproducible, with an average kappa of 0.475 (range, 0.389 to 0.598) for the agreement regarding the assignment of the three types and an average kappa of 0.537 for the agreement regarding the nine subtypes. The average kappa for the agreement regarding the assignment of the four Denis fracture types was 0.606 (range, 0.395 to 0.702), and it was 0.173 for agreement regarding the sixteen subtypes. The intraobserver agreement (repeatability) was 82% and 79% for the AO and Denis types, respectively, and 67% and 56%, for the AO and Denis subtypes, respectively. Conclusions: Both the Denis and the AO system for the classification of spine fractures had only moderate reliability and repeatability. The tendency for well-trained spine surgeons to classify the same fracture differently on repeat testing is a matter of some concern. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Twin Cities Spine Ctr, Minneapolis, MN 55404 USA. Rotham Inst Jefferson, Philadelphia, PA 19107 USA. Univ Kansas, Dept Neurosurg, Kansas City, KS 66116 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Wood, KB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,YAW 3, Boston, MA 02114 USA. EM kbwood@partners.org NR 9 TC 60 Z9 78 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2005 VL 87A IS 7 BP 1423 EP 1429 DI 10.2106/JBJS.C.01530 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 941XT UT WOS:000230248200002 PM 15995107 ER PT J AU Ring, D Prommersberger, KJ Del Pino, JG Capomassi, M Slullitel, M Jupiter, JB AF Ring, D Prommersberger, KJ Del Pino, JG Capomassi, M Slullitel, M Jupiter, JB TI Corrective osteotomy for intra-articular malunion of the distal part of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID INTERNAL-FIXATION; COLLES FRACTURE; END; DEFORMITY; ADULTS; WRIST AB Background: Corrective osteotomy is an appealing treatment for malunited articular fractures of the distal part of the radius since articular incongruity may be the factor most strongly associated with arthrosis and diminished function after such fractures. Enthusiasm for osteotomy has been limited by concerns regarding the difficulty of the technique and the potential for additional injury, osteonecrosis, and nonunion. Methods: Twenty-three skeletally mature patients were evaluated at an average of thirty-eight months after corrective osteotomy for an intra-articular malunion of the distal part of the radius. The indication for the osteotomy included dorsal or volar subluxation of the radiocarpal joint in fourteen patients and articular incongruity of >= 2 mm as measured on a posteroanterior radiograph in seventeen patients. Six patients had combined intra-articular and extra-articular malunion. The average interval from the injury to the osteotomy was six months. The average maximum step-off or gap of the articular surface prior to the operation was 4 mm. Results: One patient had a subsequent partial wrist arthrodesis because of radiocarpal arthrosis, and three patients had additional surgery because of dysfunction of the distal radioulnar joint. One patient had a rupture of the extensor pollicis longus, which was treated with a tendon transfer. The final articular incongruity averaged 0.4 mm, and the final grip strength averaged 85% of that on the contralateral side. The rate of excellent or good results was 83% according to the rating systems of Fernandez and of Gartland and Werley, and 43% according to a modification of the rating system of Green and O'Brien. Conclusions: The results of corrective osteotomy for the treatment of intra-articular malunion are comparable with those of osteotomy for the treatment of extra-articular malunion. Intra-articular osteotomy can be performed with acceptable safety and efficacy, it improves wrist function, and it may help to limit the need for salvage procedures such as partial or total wrist arthrodesis. C1 Massachusetts Gen Hosp, Yawkee Ctr, Boston, MA 02114 USA. Klin Handchirurg, D-97615 Bad Neustadt an der Saale, Germany. Virgen Torre Hosp, Div Hand Surg, Madrid 28031, Spain. Inst Ortoped & Traumatol Jaime Slullitel, Trauma Ctr, Rosario, Argentina. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 20 TC 39 Z9 39 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2005 VL 87A IS 7 BP 1503 EP 1509 DI 10.2106/JBJS.D.02465 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 941XT UT WOS:000230248200012 PM 15995117 ER PT J AU Mithoefer, K Gill, TJ Vrahas, MS AF Mithoefer, K Gill, TJ Vrahas, MS TI Supracondylar femoral fracture after arthroscopic reconstruction of the anterior cruciate ligament - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID 2-YEAR FOLLOW-UP; PATELLAR-TENDON; TUNNEL ENLARGEMENT; INTERFERENCE SCREW; CONDYLE FRACTURE; BONE STRENGTH; SURGERY; FIXATION; FEMUR; HOLE C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Mithoefer, K (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 15 Parkman St, Boston, MA 02114 USA. EM kmithoefer@partners.org NR 34 TC 9 Z9 9 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2005 VL 87A IS 7 BP 1591 EP 1596 DI 10.2106/JBJS.D.02784 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 941XT UT WOS:000230248200024 PM 15995129 ER PT J AU Erben, RG Mayer, D Weber, K Jonsson, K Juppner, H Lanske, B AF Erben, RG Mayer, D Weber, K Jonsson, K Juppner, H Lanske, B TI Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MN SP Amer Soc Bone & Mineral Res DE phosphate; PHEX; Hyp; rickets; osteoblasts; transgenic ID X-LINKED HYPOPHOSPHATEMIA; PHOSPHATE WASTING DISORDERS; D-RESISTANT RICKETS; PEX GENE; SUBCELLULAR-LOCALIZATION; PARATHYROID-HORMONE; TISSUE DISTRIBUTION; NORMAL MICE; EXPRESSION; BONE AB XLH in human and the Hyp phenotype in mice are caused by inactivating Phex mutations. Overexpression of human PHEX under the human beta-actin promoter in Hyp mice rescued the bone phenotype almost completely, but did not affect phosphate homeostasis, suggesting that different, possibly independent, pathophysiological mechanisms contribute to hyperphosphaturia and bone abnormalities in XLH. Introduction: Mutations in PHEX, a phosphate-regulating gene with homologies to endopeptidases on the X chromosome, are responsible for X-linked hypophosphatemia (XLH) in humans, and its mouse homologs, Hyp, Phex(Hyp-2J), phex(Hyp-Duk) , Gy, and Ska1. PHEX is thought to inactivate a phosphaturic factor, which may be fibroblast growth factor 23 (FGF)-23. Consistent with this hypothesis, FGF-23 levels were shown to be elevated in most patients with XLH and in Hyp mice. The aim of this study was, therefore, to examine whether transgenic overexpression of PHEX under the human beta-actin promoter would rescue the Hyp phenotype. Materials and Methods: We tested this hypothesis by generating two mouse lines expressing human PHEX under the control of a human P-actin promoter (PHEX-tg). With the exception of brain, RT-PCR analyses showed transgene expression in all tissues examined. PHEX protein, however, was only detected in bone, muscle, lung, skin, and heart. To assess the role of the mutant PHEX, we crossed female heterozygous Hyp mice with male heterozygous PHEX-tg mice to obtain wildtype (WT), PHEX-tg, Hyp, and Hyp/PHEX-tg offspring, which were examined at 3 months of age. Results: PHEX-tg mice exhibited normal bone and mineral ion homeostasis. Hyp mice showed the known phenotype with reduced body weight, hypophosphatemia, hyperphosphaturia, and rickets. Hyp/PHEX-tg mice had almost normal body weight relative to WT controls, showed a dramatic improvement in femoral BMD, almost normal growth plate width, and, despite remaining disturbances in bone mineralization, almost normal bone architecture and pronounced improvements of osteoidosis and of halo formation compared with Hyp mice. However, Hyp and Hyp/PHEX-tg mice had comparable reductions in tubular reabsorption of phosphate and were hypophosphatemic relative to WT controls. Conclusion: Our data suggest that different, possibly independent, pathophysiological mechanisms contribute to renal phosphate wasting and bone abnormalities in Hyp and XLH. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Oral & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Munich, Inst Physiol, D-8000 Munich, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Oral & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM beate_lanske@hsdm.harvard.edu RI Weber, Karin/A-6034-2016 OI Weber, Karin/0000-0002-0541-4355 FU NIDDK NIH HHS [R01 DK073944, R01 DK073944-01A2]; PHS HHS [R01 46718-10] NR 55 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2005 VL 20 IS 7 BP 1149 EP 1160 DI 10.1359/JBMR.050212 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940HK UT WOS:000230134100008 PM 15940367 ER PT J AU Li, FH Chung, H Reddy, SV Lu, GW Kurihara, N Zhao, AZ Roodman, GD AF Li, FH Chung, H Reddy, SV Lu, GW Kurihara, N Zhao, AZ Roodman, GD TI Annexin II stimulates RANKL expression through MAPK SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE annexin II; RANKL; MAPK pathway; osteoclast formation; primary human bone marrow cells ID INCREASES OSTEOCLAST FORMATION; HUMAN MARROW CULTURES; KAPPA-B LIGAND; RECEPTOR ACTIVATOR; CELLS; DIFFERENTIATION; PROTEIN; OSTEOPROTEGERIN; IDENTIFICATION; INTERLEUKIN-1 AB We report that AX-II, in addition to inducing GM-CSF expression, also increases membrane-bound RANKL synthesis by marrow stromal cells and does so through a previously unreported MAPK-dependent pathway. Thus, both GM-CSF and RANKL are required for AX-II stimulation of OCL formation. Introduction: Annexin II (AX-II) is an autocrine/paracrine factor secreted by osteoclasts (OCLs) that stimulates human OCL formation and bone resorption in vitro by inducing bone marrow stromal cells and activated CD4+ T cells to produce granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF in turn increases OCL precursor proliferation and further enhances OCL formation. However, the induction of GM-CSF by AX-II cannot fully explain its effects on OCL formation. In this study, we tested the capacity of AX-II to induce the expression of RANKL and the corresponding signaling pathways AX-II employs in human marrow stromal cells to induce RANKL. We also showed that both GM-CSF and RANKL are required for OCL formation induced by AX-II. Materials and Methods: Real-time RT-PCR and Western blot analysis were used to detect RANKL and osteoprotegerin (OPG) mRNA and protein expression in unfractionated human bone marrow mononuclear cells stimulated with AX-II. Soluble RANKL in the conditioned medium was analyzed by ELISA. Activation of the MAPK pathway by AX-II was tested by Western blot. The effects of OPG and anti-GM-CSF on AX-II-induced OCL formation were also examined. Results and Conclusion: In addition to upregulating GM-CSF mRNA, AX-II increased RANKL mRNA expression dose-dependently in unfractionated human bone marrow mononuclear cells and modestly increased soluble RANKL in unfractionated human bone marrow mononuclear cell conditioned medium. However, AX-II markedly increased membrane-bound RANKL on human bone marrow stromal cells. Treatment of marrow stromal cells with AX-II activated MAP-kinase (ERKs) and PD 98059 abolished the effect but did not block the increase in GM-CSF. Interestingly, OPG, a natural decoy receptor for RANKL, or anti-GM-CSF partially inhibited OCL formation by AX-II in human bone marrow cells, and the combination of OPG and anti-GM-CSF completely blocked AX-II-induced OCL formation. These data show that AX-II stimulates both the proliferation and differentiation of OCL precursors through production of GM-CSF and RANKL respectively. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA USA. Sungkyunkwan Univ, Samsung Cheil Hosp, Dept Med, Seoul, South Korea. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Med Hematol Oncol 111-H,Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu FU NIA NIH HHS [R01 AG13625] NR 23 TC 30 Z9 37 U1 0 U2 4 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2005 VL 20 IS 7 BP 1161 EP 1167 DI 10.1359/JBMR.050207 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940HK UT WOS:000230134100009 PM 15940368 ER PT J AU Tofovic, SP Salah, EM Dubey, RK Melhem, MF Jackson, EK AF Tofovic, SP Salah, EM Dubey, RK Melhem, MF Jackson, EK TI Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic nitric oxide synthase inhibition SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE estradiol; metabolites; cardiovascular disease; chronic renal failure ID ESTROGEN PLUS PROGESTIN; ANGIOTENSIN-II; POSTMENOPAUSAL WOMEN; DISEASE; HYPERTENSION; 2-HYDROXYESTRADIOL; GENDER; PROGRESSION; RAT; 2-METHOXYESTRADIOL AB Our previous studies in rodent models of nephropathy demonstrate that 2-hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity, exerts renoprotective effects. In vivo, 2HE is readily converted to 2-methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity. The goal of this study was to determine whether 2ME has renal and cardiovascular protective effects in vivo. First, the acute (90 minutes) and chronic (14 days) effects of 2ME (10 mu g/kg/h) on blood pressure and renal function were examined in normotensive and spontaneously hypertensive rats (SHR). Second, a rat model of cardiovascular and renal injury induced by chronic nitric oxide synthase inhibition (N-omega-nitro-L-arginine; 40 mg/kg/d; LNNA group) was used to examine the protective effects of estradiol metabolites. Subsets of LNNA-treated rats were administered either 2HE or 2ME (10 mu g/kg/h via osmotic minipump; LNNA+2ME and LNNA+2HE groups, respectively. 2-Methoxyestradiol had no acute or chronic effects on blood pressure or renal function in normotensive animals or on hypertension in SHR. Prolonged, 5-week NOS inhibition induced severe cardiovascular and renal disease and high mortality (75%, LNNA group). 2ME, but not 2HE, significantly decreased elevated blood pressure and attenuated the reduction in GFR. 2HE delayed the onset of proteinuria, whereas no proteinuria was detected in the 2-ME group. 2HE and 2ME reduced mortality rate by 66% and 83%, respectively (P < 0.001). In the kidney 2HE and 2ME abolished LNNA-induced interstitial and glomerular inflammation, attenuated glomerular collagen IV synthesis, and inhibited glomerular and tubular cell proliferation. In the heart, 2HE and 2ME markedly reduced vascular and interstitial inflammation and reduced collagen synthesis and vascular/interstitial cell proliferation. This study provides the first evidence that, in a model of severe cardiovascular and renal injury, 2-methoxyestradiol (a major nonestrogenic estradiol metabolite) exerts renal and cardiovascular protective effects and reduces mortality. C1 Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Dept Med, Pittsburgh, PA 15219 USA. VA Pittsburgh Hlth Syst, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. RP Tofovic, SP (reprint author), Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Dept Med, 100 Technol Dr,Suite 450, Pittsburgh, PA 15219 USA. EM tofovic@msx.dom.pitt.edu NR 49 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUL PY 2005 VL 46 IS 1 BP 25 EP 35 DI 10.1097/01.fjc.0000162765.89437.ae PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 940PH UT WOS:000230155900004 PM 15965351 ER PT J AU Mukhopadhyay, NK Gordon, GJ Maulik, G Doerre, G Liu, BCS Bueno, R Sugarbaker, DJ Jaklitsch, MT AF Mukhopadhyay, NK Gordon, GJ Maulik, G Doerre, G Liu, BCS Bueno, R Sugarbaker, DJ Jaklitsch, MT TI Histone deacetylation is directly involved in desilencing the expression of the catalytic subunit of telomerase in normal lung fibroblast SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE histone deacetylation; h-TERT; gene silencing; telomerase ID NORMAL HUMAN-CELLS; TRANSCRIPTIONAL REPRESSION; CANCER-CELLS; C-MYC; GENE; ACTIVATION; PROTEIN; HTERT; INHIBITION; ADHESION AB The regulation of telomerase expression in normal cells is poorly understood. Moreover, the molecular mechanism underlying tumor-specific expression of telomerase remains unclear. We investigated the link between histone deacetylation and telomerase activity in normal lung and lung tumor cells. Four non-small-cell lung cancer (NSCLC) lines and one normal lung fibroblast line were tested for telomerase activity with or without Trichostatin A (TSA). The telomerase activity and the expression of telomerase associated components were determined by TRAP assay, RT PCR analysis and Western blot analysis. All 4 NSCLC cell lines exposed to 1 mu M TSA for 24h had no change in telomerase activity or hTERT mRNA level. Telomerase activity was very low in normal lung fibroblasts (mrc-9) until exposed to 1 mu M TSA for 24h, at which time telomerase activity was readily detectable, with concomitant upregulation of hTERT mRNA (10-fold). The level of other telomerase associated components (hTER and TP1) were unaltered. Furthermore, 1 mu M TSA exposure for 24h did not alter the level of c-Myc or p21 mRNA. Immunodetection reveled that hTERT protein expression increased (similar to 6 fold) compared to c-Myc, p21, or gelsolin. The effect of TSA on hTERT expression is independent of DNA methylation as judged by 5-azacytidine (5aza) treatment. TSA effect on mrc-9 cells is unaltered even in the presence of 200 mu g/ml cyclohexamide, suggesting a direct inhibition of histone deacetylation. Collectively, our study indicates that inhibition of histone deacetylation selectively regulates the transcriptional derepression of telomerase catalytic subunit in normal lung fibroblast cells compared to lung tumor cells. C1 Harvard Univ, Div Thorac Surg, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Div Urol Surg, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. RP Jaklitsch, MT (reprint author), Harvard Univ, Div Thorac Surg, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mtjaklitsch@partners.org NR 34 TC 13 Z9 16 U1 1 U2 1 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUL-SEP PY 2005 VL 9 IS 3 BP 662 EP 669 DI 10.1111/j.1582-4934.2005.tb00496.x PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 975RT UT WOS:000232680300013 PM 16202213 ER PT J AU Kim, YR Huang, IJ Lee, SR Tejima, E Mandeville, JB van Meer, MPA Dai, G Choi, YW Dijkhuizen, RM Lo, EH Rosen, BR AF Kim, YR Huang, IJ Lee, SR Tejima, E Mandeville, JB van Meer, MPA Dai, G Choi, YW Dijkhuizen, RM Lo, EH Rosen, BR TI Measurements of BOLD/CBV ratio show altered fMRI hemodynamics during stroke recovery in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BOLD; CBV; fMRI; MCAO; stroke; thalamus ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-VOLUME; FOREPAW STIMULATION; MOTOR RECOVERY; BRAIN; REORGANIZATION; ANGIOGENESIS; MRI AB Brain responses to external stimuli after permanent and transient ischemic insults have been documented using cerebral blood volume weighted (CBVw) functional magnetic resonance imaging (fMRI) in correlation with tissue damage and neurological recovery. Here, we extend our previous studies of stroke recovery in rat models of focal cerebral ischemia by comparing blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) changes. Responses to forepaw stimulation were measured in normal rats (n=5) and stroke rats subjected to 2h of middle cerebral artery occlusion (n=6). Functional magnetic resonance imaging was performed 2 weeks after stroke to evaluate the recovery process. After stroke, animals showed variable degrees of fMRI activation in lipsilesional cortex, the extent of which did not correlate with structural damages as measured using apparent diffusion coefficient, fractional anisotropy, blood volume, and vessel size index. While the contralesional cortex showed good overlap between BOLD and CBV-activated regions, the ipsilesional cortex showed low covariance between significantly activated voxels by BOLD and CBVw techniques. In particular, the relative activation during contralateral stimuli in the ipsilesional somatosensory cortex was significantly higher for CBVw responses than BOLD, which might be due to stroke-related alterations in fMRI hemodynamic coupling. Aberrant subcortical activations were also observed. When unaffected forelimbs were stimulated, strong bilateral responses were observed. However, little thalamic responses accompanied stimulation of affected forelimbs despite significant activation in the ipsilesional somatosensory cortex. These results suggest that stroke affects not only local hemodynamics and coupling but also other factors including neural connectivity. C1 Massachusetts Gen Hosp, MIT, HMS,Neuroprotect Lab, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Univ Utrecht, Med Ctr, Image Sci Inst, Utrecht, Netherlands. Microsyst Technol Labs, Cambridge, MA USA. RP Kim, YR (reprint author), Massachusetts Gen Hosp, MIT, HMS,Neuroprotect Lab, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St Room 2301, Charlestown, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu RI Dijkhuizen, Richard/A-6506-2008 FU NIBIB NIH HHS [501EB002066] NR 21 TC 34 Z9 37 U1 0 U2 4 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 JUL PY 2005 VL 25 IS 7 BP 820 EP 829 DI 10.1038/sj.jcbfm.9600084 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 940CW UT WOS:000230122300004 PM 15758949 ER PT J AU Kim, DE Schellingerhout, DT Jaffer, FA Weissleder, R Tung, CH AF Kim, DE Schellingerhout, DT Jaffer, FA Weissleder, R Tung, CH TI Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis (vol 25, pg 226, 2005) SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Correction C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med,Cardiol Div, Boston, MA 02115 USA. RP Kim, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 2 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 JUL PY 2005 VL 25 IS 7 BP 937 EP 937 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 940CW UT WOS:000230122300016 ER PT J AU Doyle, AE Faraone, SV Seidman, LJ Willcutt, EG Nigg, JT Waldman, ID Pennington, BF Peart, J Biederman, J AF Doyle, AE Faraone, SV Seidman, LJ Willcutt, EG Nigg, JT Waldman, ID Pennington, BF Peart, J Biederman, J TI Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD? SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Review DE ADHD; endophenotype; genetics; neuropsychology; executive functions ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE-D4 RECEPTOR GENE; DSM-IV ADHD; RESPONSE-INHIBITION DEFICIT; FAMILY-BASED ASSOCIATION; AFFECTED SIBLING PAIRS; PERFORMANCE-TEST TOVA; DISCORDANT SIB PAIRS; CARD SORTING TEST AB Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. Method: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. Results: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. Conclusions: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Colorado, Boulder, CO 80309 USA. Michigan State Univ, E Lansing, MI 48824 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Denver, Denver, CO 80208 USA. RP Doyle, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM doylea@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08-MH-66072, K01-MH01818, R01 MH59105, R21-MH066191] NR 226 TC 129 Z9 132 U1 9 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUL PY 2005 VL 46 IS 7 BP 774 EP 803 DI 10.1111/j.1469-7610.2005.01476.x PG 30 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 938LY UT WOS:000230006100007 PM 15972070 ER PT J AU Antin, JH AF Antin, JH TI Donor leukocyte infusions and graft-versus-malignancy SO JOURNAL OF CLINICAL APHERESIS LA English DT Article; Proceedings Paper CT 10th Congress of the World-Apheresis-Association held at the 25th Annual Meeting of the American-Society-for-Apheresis CY MAY 05-08, 2004 CL Miami Beach, FL SP World Apheres Assoc, Amer Soc Apheres ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; 1ST CHRONIC PHASE; HOST-DISEASE; ADOPTIVE IMMUNOTHERAPY; LYMPHOCYTE INFUSION; IMPROVED SURVIVAL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Oncol Stem Cell Transpl, Boston, MA 02115 USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jantin@partners.org NR 33 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PD JUL PY 2005 VL 20 IS 2 BP 113 EP 116 DI 10.1002/jca.20040 PG 4 WC Hematology SC Hematology GA 948EY UT WOS:000230700000011 PM 15880356 ER PT J AU Yehuda, R Engel, SM Brand, SR Seckl, J Marcus, SM Berkowitz, GS AF Yehuda, R Engel, SM Brand, SR Seckl, J Marcus, SM Berkowitz, GS TI Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the world trade center attacks during pregnancy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTISOL-LEVELS; HOLOCAUST SURVIVORS; PTSD; TRAUMA; RISK AB Context: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder ( PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. 3 Objective: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. Design: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. Results: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. Conclusions: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD. C1 Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, Bronx, NY 10471 USA. Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Dept Community & Prevent Med, Bronx, NY 10471 USA. Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Div Biostat, Bronx, NY 10471 USA. Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, Bronx, NY 10471 USA. RI Seckl, Jonathan/C-3555-2013 FU NIEHS NIH HHS [P42 ES07384]; NIMH NIH HHS [5 R01 MH64675-03] NR 20 TC 242 Z9 260 U1 4 U2 35 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2005 VL 90 IS 7 BP 4115 EP 4118 DI 10.1210/jc.2005-0550 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FT UT WOS:000230339100047 PM 15870120 ER PT J AU Melmed, S Sternberg, R Cook, D Klibanski, A Chanson, P Bonert, V Vance, ML Rhew, D Kleinberg, D Barkan, A AF Melmed, S Sternberg, R Cook, D Klibanski, A Chanson, P Bonert, V Vance, ML Rhew, D Kleinberg, D Barkan, A TI CLINICAL REVIEW: A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PREOPERATIVE OCTREOTIDE TREATMENT; HORMONE RECEPTOR ANTAGONIST; GROWTH-FACTOR-I; ADENOMAS; MORTALITY; VOLUME; HYPERSECRETION; MACROADENOMAS; MULTICENTER; CABERGOLINE AB Context: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases. Evidence Acquisition: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction. Evidence Synthesis: Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% ( weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients. Conclusions: Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA. Zynx Hlth Inc, Los Angeles, CA 90024 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97205 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Hop Bicetre, Dept Endocrinol, F-94275 Paris, France. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA 22901 USA. NYU, Med Ctr, Dept Med, New York, NY 10010 USA. Univ Michigan, Vet Adm Med Ctr, Dept Med, Ann Arbor, MI 48105 USA. RP Melmed, S (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Dept Med, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM melmed@csmc.edu RI Chanson, Philippe/F-8511-2013 NR 35 TC 126 Z9 134 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2005 VL 90 IS 7 BP 4405 EP 4410 DI 10.1210/jc.2004-2466 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FT UT WOS:000230339100093 PM 15827109 ER PT J AU Traina, SB MacLean, CH Park, GS Kahn, KL AF Traina, SB MacLean, CH Park, GS Kahn, KL TI Telephone reminder calls increased response rates to mailed study consent forms SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE increasing; mail; response rates; rheumatoid arthritis; telephone calls ID QUESTIONNAIRE; PHYSICIANS; ARTHRITIS AB Background: This study assessed the impact of follow-up reminder phone calls on response rates to a mailed consent form packet. Methods: Patients with rheumatoid arthritis were invited to enroll in a study by signing and returning consent forms by mail. Patients not returning completed study consent forms were called and reminded to return the signed consent forms. Results: Among 724 mailed consent form packets, 376 (52%) were returned without further follow-up. Follow-up reminder calls were made to 220 of the 348 patients who did not return signed consent forms. Among subjects contacted by phone, 67 (31% of those called) returned signed consent forms. Conclusion: Follow-up reminder phone calls raised the overall consent rate of 52 to 61%, suggesting that they can be an effective technique in increasing response rates. (c) 2005 Elsevier Inc. All rights reserved. C1 VA Greater LA Healthcare Syst, Div Rheumatol W 111J, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol W 111J, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. RP Traina, SB (reprint author), VA Greater LA Healthcare Syst, Div Rheumatol W 111J, Los Angeles, CA 90073 USA. EM straina@mednet.ucla.edu NR 15 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 2005 VL 58 IS 7 BP 743 EP 746 DI 10.1016/j.jclinepi.2005.02.001 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 938YB UT WOS:000230038200016 PM 15939228 ER PT J AU Ly, NP Li, Y Sredl, DL Perkins, DL Finn, PW Weiss, ST Gold, DR AF Ly, NP Li, Y Sredl, DL Perkins, DL Finn, PW Weiss, ST Gold, DR TI Elevated allergen-induced IL-13 secretion predicts IgE elevation in children ages 2-5 years SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE children; IFN-gamma; IL-13; IL-4; IgE; PBMCs ID INTERFERON-GAMMA PRODUCTION; T-CELLS; IMMUNOLOGICAL MEMORY; INHALANT ALLERGENS; ATOPIC-DERMATITIS; SERUM IGE; ASTHMA; DISEASE; EXPRESSION; RESPONSES AB It is unclear if early immune responses to allergens, specifically Th1 and Th2 cytokine production, predict later immune responses, including increased IgE levels. In a group of children (n = 151) with a parental history of allergy or asthma followed from ages 2 through 5 years, we examined IL-13, IL-4, and IFN-gamma secretion by peripheral blood mononuclear cells in response to phytohemagglutinin (PHA), and to dust mite (Der f 1), cockroach (Bla g 2), and cat (Fel d 1) allergens in relation to elevated IgE. Elevated IgE was defined either as a positive IgE-specific response to at least one allergen (dust mite, cockroach, cat, and ovalbumin) or as an elevated total IgE level above a specified cut-off value. In multivariate logistic regression models including 181 observations made between the age of 2 through 5 years and accounting for repeated measures, we found an association between increased IL-13 secretion in response to Der f 1 and elevated IgE (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.09-1.34). Age did not modify this relationship. No association was found between allergen-induced IFN-gamma secretion and IgE production. Among the group of children with measurements made at age 4-5 (n = 70), IL-13 in response to Der f 1 (p = 0.046), and IL-4 in response to PHA (p = 0.04) were increased among children with elevated IgE. In a smaller subset of children with measurements made at both age 2-3 and age 4-5 (n = 36), IL-13 levels at age 2-3 were also significantly increased in response to Der f 1 (p = 0.01) and Fel d 1 (p = 0.002) among those with elevated IgE at age 4-5. In a group of children ages 2-5 years, there is an association between IL-13 and elevated IgE. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Pediat Pulm Div, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ly, NP (reprint author), 181 Longwood Ave,4th Floor, Boston, MA 02115 USA. EM renpl@channing.harvard.edu FU NHLBI NIH HHS [HL07427]; NIAID NIH HHS [AI/EHS35786, AI 45007, AI/EHS45007] NR 26 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 2005 VL 25 IS 4 BP 314 EP 320 DI 10.1007/s10875-005-4699-5 PG 7 WC Immunology SC Immunology GA 956RI UT WOS:000231317100003 PM 16133987 ER PT J AU Kobayashi, T Soegiarto, DW Yang, YZ Lanske, B Schipani, E McMahon, AP Kronenberg, HM AF Kobayashi, T Soegiarto, DW Yang, YZ Lanske, B Schipani, E McMahon, AP Kronenberg, HM TI Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; PARATHYROID-HORMONE; EXPRESSION; PROLIFERATION; RECEPTOR; PROGRESSION; PRECURSORS; PROTEIN; GENE AB In the developing growth plate, periarticular chondrocytes proliferate, differentiate into columnar chondrocytes, and then further differentiate into postmitotic hypertrophic chondrocytes. Parathyroid hormone-related (PTH-related) protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, thereby maintaining the length of columns. Ihh regulates cartilage development through PTHrP-independent pathways as well. Here we show that Ihh stimulates differentiation of periarticular to columnar chondrocytes (periarticular chondrocyte differentiation) and thereby regulates the length of columns independently of PTHrP. Mosaic ablation of the PTH/PTHrP receptor in the growth plate caused upregulation of Ihh action, PTHrP upregulation, acceleration of periarticular chondrocyte differentiation, and elongation of the columnar region. Decreasing Ihh action in these mice reduced elongation of columns, whereas decreasing PTHrP showed only a modest effect on column length. Overexpression of Ihh caused PTHrP upregulation, elongation of columns, and acceleration of periarticular chondrocyte differentiation. PTHrP heterozygosity in this model had a minimal effect on the elongation of columns. Moreover, the elongation of columns and stimulation of periarticular chondrocyte differentiation in these models were still observed when PTHrP signaling was maintained so that it remained constant. These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA. Forsyth Inst, Dept Oral & Dev Biol, Boston, MA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU NIDDK NIH HHS [DK56246, P01 DK056246] NR 26 TC 127 Z9 139 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1734 EP 1742 DI 10.1172/JCI24397 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800013 PM 15951842 ER PT J AU Duffield, JS Park, KM Hsiao, LL Kelley, VR Scadden, DT Ichimura, T Bonventre, JV AF Duffield, JS Park, KM Hsiao, LL Kelley, VR Scadden, DT Ichimura, T Bonventre, JV TI Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE-RENAL-FAILURE; BETA-GALACTOSIDASE ACTIVITY; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; STROMAL CELLS; RAT-KIDNEY; INJURY; MICE; TRANSPLANTATION AB Ischemia causes kidney tubular cell damage and abnormal renal function. The kidney is capable of morphological restoration of tubules and recovery of function. Recently, it has been suggested that cells repopulating the ischemically injured tubule derive from bone marrow stem cells. We studied kidney repair in chimeric mice expressing GFP or bacterial P-gal or harboring the male Y chromosome exclusively in bone marrow-derived cells. In GFP chimeras, some interstitial cells but not tubular cells expressed GFP after ischemic injury. More than 99% of those GFP interstitial cells were leukocytes. In female mice with male bone marrow, occasional tubular cells (0.06%) appeared to be positive for the Y chromosome, but deconvolution microscopy revealed these to be artifactual. In beta-gal chimeras, some tubular cells also appeared to express beta-gal as assessed by X-gal staining, but following suppression of endogenous (mammalian) beta-gal, no tubular cells could be found that stained with X-gal after ischemic injury. Whereas there was an absence of bone marrow-derived tubular cells, many tubular cells expressed proliferating cell nuclear antigen, which is reflective of a high proliferative rate of endogenous surviving tubular cells. Upon i.v. injection of bone marrow mesenchymal stromal. cells, postischemic functional renal impairment was reduced, but there was no evidence of differentiation of these cells into tubular cells of the kidney. Thus, our data indicate that bone marrow-derived cells do not make a significant contribution to the restoration of epithelial integrity after an ischemic insult. It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia. C1 Harvard Univ, Brigham & Womens Hosp, Inst Med, Renal Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Bonventre, JV (reprint author), Harvard Univ, Brigham & Womens Hosp, Inst Med, Renal Div, 5th Floor,4 Blackfan Circle, Boston, MA 02115 USA. EM joseph_bonventre@hnis.harvard.edu FU NIDDK NIH HHS [DK 39773, DK 38452, P01 DK038452, R01 DK039773, R37 DK039773] NR 61 TC 379 Z9 418 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1743 EP 1755 DI 10.1172/JCI22593 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800014 PM 16007251 ER PT J AU Gorgun, G Holderried, TAW Zahrieh, D Neuberg, D Gribben, JG AF Gorgun, G Holderried, TAW Zahrieh, D Neuberg, D Gribben, JG TI Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED PROTEIN-KINASE; B-CELLS; IMMUNOLOGICAL SYNAPSE; MEDIATED ACTIVATION; MOLECULAR-CLONING; BINDING PROTEIN; DENDRITIC CELLS; HUMAN MONOCYTES; TH1 CELLS; INTERLEUKIN-10 AB To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA USA. Queen Mary Univ London, Canc Res United Kingdom, Barts & London Sch Med, Dept Med Oncol, London EC1M 6BQ, England. RP Gribben, JG (reprint author), St Bartholomews Hosp, Canc Res United Kingdom Med Oncol Unit, Barts & London Sch Med, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk FU NCI NIH HHS [P01 CA81538] NR 53 TC 130 Z9 131 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1797 EP 1805 DI 10.1172/JCI24176 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800019 PM 15965501 ER PT J AU Kashiwagi, S Izumi, Y Gohongi, T Demou, ZN Xu, L Huang, PL Buerk, DG Munn, LL Jain, RK Fukumura, D AF Kashiwagi, S Izumi, Y Gohongi, T Demou, ZN Xu, L Huang, PL Buerk, DG Munn, LL Jain, RK Fukumura, D TI NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; DEPENDENT PROTEIN-KINASE; IN-VIVO; FLUORESCENT INDICATOR; VASCULAR-PERMEABILITY; INDUCED ANGIOGENESIS; MOLECULAR REGULATION; DEFICIENT MICE AB NO has been shown to mediate angiogenesis; however, its role in vessel morphogenesis and maturation is not known. Using intravital microscopy, histological analysis, a-smooth muscle actin and chondroitin sulfate proteoglycan 4 staining, microsensor NO measurements, and an NO synthase (NOS) inhibitor, we found that NO mediates mural cell coverage as well as vessel branching and longitudinal extension but not the circumferential growth of blood vessels in B16 murine melanomas. NO-sensitive fluorescent probe 4,5-diaminofluorescein imaging, NOS immunostaining, and the use of NOS-deficient mice revealed that eNOS in vascular endothelial cells is the predominant source of NO and induces these effects. To further dissect the role of NO in mural cell recruitment and vascular morphogenesis, we performed a series of independent analyses. Transwell and under-agarose migration assays demonstrated that endothelial cell-derived NO induces directional migration of mural cell precursors toward endothelial cells. An in vivo tissue-engineered blood vessel model revealed that NO mediates endothelial-mural cell interaction prior to vessel perfusion and also induces recruitment of mural cells to angiogenic vessels, vessel branching, and longitudinal extension and subsequent stabilization of the vessels. These data indicate that endothelial cell-derived NO induces mural cell recruitment as well as subsequent morphogenesis and stabilization of angiogenic vessels. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,COX-7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu RI Buerk, Donald/F-6888-2014; Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R01-CA96915, R24 CA085140, R01 CA096915, R24-CA85140]; NHLBI NIH HHS [R01 HL068164, HL-068164] NR 63 TC 103 Z9 104 U1 2 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1816 EP 1827 DI 10.1172/JCI124015 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800021 PM 15951843 ER PT J AU Partridge, AH Winer, EP AF Partridge, AH Winer, EP TI Fertility after breast cancer: Questions abound SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CRYOPRESERVED OVARIAN TISSUE; PREMENOPAUSAL WOMEN; YOUNG-WOMEN; TAMOXIFEN; TRANSPLANTATION; THERAPY; HORMONE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 17 TC 8 Z9 9 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 JUL 1 PY 2005 VL 23 IS 19 BP 4259 EP 4261 DI 10.1200/JCO.2005.12.914 PG 3 WC Oncology SC Oncology GA 943DP UT WOS:000230332800005 PM 15824413 ER PT J AU Perlis, RH Keck, PE AF Perlis, RH Keck, PE TI The Texas Implementation of Medication Algorithms update for treatment of bipolar I disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID CONFLICTS-OF-INTEREST; DEPRESSION; PRAMIPEXOLE; IMPACT C1 Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Gen Clin Res Ctr, Cincinnati, OH USA. Cincinnati Vet Affairs Med Ctr, Mental Hlth Care Line, Cincinnati, OH USA. RP Perlis, RH (reprint author), Bipolar Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org NR 11 TC 12 Z9 12 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2005 VL 66 IS 7 BP 818 EP 820 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 947RL UT WOS:000230663800002 PM 16013895 ER PT J AU Finn, CT Wilcox, MA Korf, BR Blacker, D Racette, SR Sklar, P Smoller, JW AF Finn, CT Wilcox, MA Korf, BR Blacker, D Racette, SR Sklar, P Smoller, JW TI Psychiatric genetics: A survey of psychiatrists' knowledge, opinions, and practice patterns SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PRIMARY-CARE PHYSICIANS; COUNSELING FOLLOWING DIAGNOSIS; BIPOLAR DISORDER; SUSCEPTIBILITY GENES; NATIONAL-INSTITUTE; ALCOHOL DEPENDENCE; ALZHEIMER-DISEASE; FETAL-ABNORMALITY; MAJOR DEPRESSION; CYSTIC-FIBROSIS AB Objective: Knowledge about the genetic basis of psychiatric illness is growing rapidly, and psychiatrists may be called upon to incorporate this information into clinical practice. The goal of this study was to assess psychiatrists' familiarity with and attitudes toward genetic information. Method: We surveyed 844 participants, the majority of whom were psychiatrists, attending a continuing medical education course in the fall of 2002 and measured knowledge, opinions, and current practice patterns in regard to psychiatric genetics. Results: Responses were received from 352 psychiatrists (54% of those surveyed). Most psychiatrists correctly answered fewer than half of survey items assessing general and psychiatric genetic knowledge. While 83% considered it their role to discuss genetic information with patients and families, fewer than 25% felt prepared or competent to do so. In response to hypothetical questions regarding genetic testing, a substantial proportion of psychiatrists indicated willingness to use such tests for diagnostic clarification, as well as presymptomatic and even prenatal risk prediction. The majority of respondents expressed interest in further genetics education. Conclusions: Our results suggest that psychiatrists view genetic information as clinically relevant. but have limitations in knowledge that may impact the incorporation of psychiatric Genetics into clinical practice. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA. Boston Univ, Sch Med, Genet Program, Boston, MA USA. Univ Alabama, Birmingham, AL USA. Broad Inst, Boston, MA USA. RP Finn, CT (reprint author), 77 Ave Louis Pasteur,Suite 250, Boston, MA 02115 USA. EM cfinn@partners.org FU NHGRI NIH HHS [R01 HG01831]; NIMH NIH HHS [K-08 MH01770-02] NR 59 TC 37 Z9 37 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2005 VL 66 IS 7 BP 821 EP 830 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 947RL UT WOS:000230663800003 PM 16013896 ER PT J AU Stewart, SE Jenike, MA Keuthen, NJ AF Stewart, SE Jenike, MA Keuthen, NJ TI Severe obsessive-compulsive disorder with and without comorbid hair pulling: Comparisons and clinical implications SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MGH HAIRPULLING SCALE; SPECTRUM DISORDERS; EARLY-ONSET; LONG-TERM; TRICHOTILLOMANIA; RELIABILITY; VALIDITY; PLACEBO; SYMPTOM AB Objective: Chronic hair pulling and trichotillomania are putative obsessive-compulsive spectrum disorders. This study determined the prevalence of hair Pulling in an inpatient obsessive-compulsive disorder (OCD) population and compared clinical characteristics and treatment response between subgroups with and without comorbid hair-pulling. Method: Patients with severe DSM-TV-diagnosed OCD (N = 154) who were consecutively admitted to an OCD residential treatment facility between August 2000 and July 2003 were included. Clinician-rated (Yale-Brown Obsessive Compulsive Scale) and patient-rated (Massachusetts General Hospital Hairpulling Scale, Beck Depression Inventory, and Posttraumatic Diagnostic Scale) measures were administered at index evaluation. OCD patients with and without moderate to severe hair pulling were statistically compared on clinical and treatment characteristics and treatment response. Results: Of the OCD subjects, 18.8% (N = 29) endorsed any hair pulling, 15.6% (N = 24) had moderate to severe hair pulling, and 7.8% (N = 12) had severe hair pulling comparable to that of a specialty trichotillomania clinic population. OCD patients with moderate to severe hair pulling were more likely to be women (p <.001), endorse > I comorbid tic (p <.05), and have earlier-onset OCD (p =.001). This cohort also had fewer contamination obsessions (p =.04) and checking compulsions (p =.04) and was more likely to be receiving stimulant (p =.006) or venlafaxine (p =.02) medication than those patients without hair pulling. Posttraumatic Diagnostic Scale scores were nearly significantly higher in the OCD + hair pulling group (p =.08). 0 CD treatment response was unaffected by the presence of comorbid hair pulling. Conclusion: Hair pulling is a highly common comorbidity in severe OCD. Women and early-onset OCD patients appear to be more vulnerable to comorbid hair pulling. OCD sufferers with comorbid hair pulling also exhibit an increased risk for tics and may present with different OCD symptomatology. C1 McLean Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Stewart, SE (reprint author), Massachusetts Gen Hosp E, Psychiat & Neurodev Genet Unit, 10th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. EM sevelynstewart@hotmail.com RI Citations, TLC SAB/C-4006-2011; Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 52 TC 16 Z9 18 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2005 VL 66 IS 7 BP 864 EP 869 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 947RL UT WOS:000230663800009 PM 16013902 ER PT J AU Bartling, SH Shukla, V Becker, H Brady, TJ Hayman, A Gupta, R AF Bartling, SH Shukla, V Becker, H Brady, TJ Hayman, A Gupta, R TI High-resolution computed tomography of temporal bone Part II: Coronal preoperative anatomy SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE anatomy temporal bone; computed tomography temporal bone; surgery temporal bone; flat-panel detector; computed tomography ID CT AB The purpose of this 4-part series is to demonstrate the high-resolution axial and coronal anatomy of temporal bone from a flat-panel detector-based volume computed tomography (CT) scanner (parts I and II); these imaging planes are then used to outline the effect of different surgical procedures commonly applied to the temporal bone (parts III and IV). The structures that are removed and/or altered in 11 different surgical procedures are color coded and inscribed in axial and coronal sections. Clinically important imaging features and complications after these operations are also discussed. In these high-resolution images, many structures that are below the resolution limit of conventional CT can be seen and localized. It is hoped that this exposition enables one to visualize these structures and surgeries in the mind's eye, even when they fall below the resolution limit using a conventional CT scanner. This article (part II) focuses on the preoperative coronal anatomy. C1 Hannover Med Sch, Dept Neuroradiol, D-30625 Hannover, Germany. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bartling, SH (reprint author), Hannover Med Sch, Dept Neuroradiol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM soenkebartling@gmx.de NR 4 TC 6 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2005 VL 29 IS 4 BP 566 EP 569 DI 10.1097/01.rct.0000171239.18301.96 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 950BI UT WOS:000230832200026 PM 16012320 ER PT J AU Levine, M Wong, D Brown, DFM Nadel, ES AF Levine, M Wong, D Brown, DFM Nadel, ES TI Case presentations of the Harvard emergency medicine residency - Chest pain and arthritis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE RHEUMATIC-FEVER; HEART; THROAT; CHAIN; LINKS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Mt Auburn Hosp, Dept Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2005 VL 29 IS 1 BP 91 EP 95 DI 10.1016/j.jemermed.2005.04.001 PG 5 WC Emergency Medicine SC Emergency Medicine GA 938XA UT WOS:000230035500018 PM 15961016 ER PT J AU Khachemoune, A Janjua, SA AF Khachemoune, A Janjua, SA TI Pits on the soles of the feet - Diagnosis: Pitted keratolysis SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. Ayza Skin & Res Ctr, Lalamusa, Pakistan. RP Khachemoune, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, 40 Blossom St,BAR 314, Boston, MA 02114 USA. EM amorkh@pol.net NR 5 TC 2 Z9 2 U1 0 U2 0 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD JUL PY 2005 VL 54 IS 7 BP 597 EP 598 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 957OJ UT WOS:000231379000008 PM 16009086 ER PT J AU Takahashi, TA Johnson, KM Bradley, KA AF Takahashi, TA Johnson, KM Bradley, KA TI A population-based study of HIV testing practices and perceptions in 4 US states SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE HIV; HIV risk perception; HIV risk behaviors; sexual behavior; testing practices ID UNITED-STATES; RISK; BEHAVIOR; ADULTS; CARE AB OBJECTIVE: To evaluate testing practices and perceptions of HIV risk among a geographically diverse, population-based sample of sexually active adults who reported behaviors that could transmit HIV. DESIGN: Secondary analysis of the Centers for Disease Control and Preventions Behavioral Risk Factor Surveillance System (BRFSS) 2000 survey. PATIENTS/PARTICIPANTS: Sexually active adults less than 50 years old, who completed the Sexual Behavior Module of the BRFSS 2000 survey administered in 4 U. S. states. MEASUREMENTS AND MAIN RESULTS: Nineteen percent of the study population reported one or more behaviors in the past year that increased their risk of HIV infection (men 23%; women 15%). In this subgroup at any increased risk of HIV infection, 49% reported having had an HIV test in the past year. For 71% of those tested, the HIV test was self-initiated. Younger age was the only factor independently associated with whether or not individuals with behaviors that increased their risk of HIV infection had had a recent HIV test. Among the 51% of individuals at risk who reported no recent HIV test, 84% perceived their risk as low or none. CONCLUSIONS: In this study, about half of the individuals who reported behaviors that could transmit HIV had not been recently tested for HIV. Of those not tested, most considered their risk of HIV to be low or none. Interventions to expand HIV testing and increase awareness of HIV risk appear to be needed to increase early detection of HIV infection and to reduce its spread. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Takahashi, TA (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, 1660 S Columbian Way, Seattle, WA 98108 USA. EM traci@u.washington.edu FU NIAAA NIH HHS [K23 AA000313, K23AA00313]; NIDA NIH HHS [R03DA14518] NR 20 TC 14 Z9 14 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2005 VL 20 IS 7 BP 618 EP 622 DI 10.1111/j.1525-1497.2005.0112.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 942OD UT WOS:000230290800010 PM 16050856 ER PT J AU Zipser, RD Farid, M Baisch, D Patel, B Patel, D AF Zipser, RD Farid, M Baisch, D Patel, B Patel, D TI Physician awareness of Celiac disease - A need for further education SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-College-of-Gastroenterology CY OCT 10-15, 2003 CL Baltimore, MD SP Amer Coll Gastroenterol DE celiac disease; primary care physicians; endomysial antibodies; education ID PREVALENCE; MULTICENTER; SPRUE AB BACKGROUND: Celiac disease is a common disorder (up to 0.7%); however, it is uncommonly diagnosed in the United States. OBJECTIVE: We sought to determine physician awareness of celiac disease. DESIGN: Surveys completed by 2,440 (47%) of 5,191 patients in a support group were analyzed for frequency of diagnosis by physician specialties. Questionnaires were then sent to primary care physicians (PCPs) ( n= 132) in a southern California county to assess knowledge of celiac disease. RESULTS: In patient surveys, only 11% were diagnosed by PCPs (internists and family physicians) versus 65% by gastroenterologists. Physician surveys (70% response) showed that only 35% of PCPs had ever diagnosed celiac disease. Almost all physicians (95%) knew of wheat intolerance, but few (32%) knew that onset of symptoms in adulthood is common. Physicians were well aware (90%) of diarrhea as a symptom, but fewer knew of common symptoms of irritable bowel syndrome (71%), chronic abdominal pain (67%), fatigue (54%), depression and irritability (24%) or of associations with diabetes (13%), anemia (45%) or osteoporosis (45%), or of diagnosis by endomysial antibody tests (44%). CONCLUSIONS: Lack of physician awareness of adult onset of symptoms, associated disorders, and use of serology testing may contribute to the underdiagnosis of celiac disease. C1 Univ Calif Los Angeles, Med Ctr, Torrance, CA 90509 USA. W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. Celiac Dis Fdn, Studio City, CA USA. RP Zipser, RD (reprint author), 1330 W Covina Blvd,Suite 205, San Dimas, CA 91773 USA. EM rzipser@msn.com NR 18 TC 18 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2005 VL 20 IS 7 BP 644 EP 646 DI 10.1111/j.1525-1497.2005.0107.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 942OD UT WOS:000230290800015 PM 16050861 ER PT J AU Bent, S Goldberg, H Padula, A Avins, AL AF Bent, S Goldberg, H Padula, A Avins, AL TI Spontaneous bleeding associated with Ginkgo biloba - A case report and systematic review of the literature SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE herbal medicine; alternative medicine; bleeding ID GINGKO-BILOBA; DOUBLE-BLIND; HEMORRHAGE; INGESTION; EXTRACT; HEALTHY AB BACKGROUND: Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding. OBJECTIVE: To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding. DATA SOURCES: We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions. REVIEW METHODS: Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event. RESULTS: Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo. CONCLUSION: A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk. C1 San Francisco VA Med Ctr, Dept Med, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Family Practice, San Francisco, CA 94143 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, Dept Med, Gen Internal Med Sect, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM bent@itsa.ucsf.edu FU NCCIH NIH HHS [1 K08 ATO1338-01, K08 AT001338] NR 29 TC 77 Z9 83 U1 1 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2005 VL 20 IS 7 BP 657 EP 661 DI 10.1111/j.1525-1497.2005.0121.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 942OD UT WOS:000230290800019 PM 16050865 ER PT J AU Sweadner, KJ Penniston, JT AF Sweadner, KJ Penniston, JT TI Na,K-ATPase alpha subunit mutations in neurological disease. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 12 BP 6A EP 6A PG 1 WC Physiology SC Physiology GA 943XI UT WOS:000230388500020 ER PT J AU Faller, LD Lin, SH AF Faller, LD Lin, SH TI Implications of dependence on ionic strength for the mechanism of the conformational change in unphosphorylated sodium pump. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 58 BP 26A EP 26A PG 1 WC Physiology SC Physiology GA 943XI UT WOS:000230388500066 ER PT J AU Faller, LD Nagy, AK Diaz, UA Farley, RA AF Faller, LD Nagy, AK Diaz, UA Farley, RA TI Oxygen exchange studies of the phosphoryl group transfer mechanism. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 59 BP 26A EP 27A PG 2 WC Physiology SC Physiology GA 943XI UT WOS:000230388500067 ER PT J AU Shin, JM Sachs, G AF Shin, JM Sachs, G TI Oligomeric functional form of the gastric H,K-ATPase. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 90 BP 40A EP 40A PG 1 WC Physiology SC Physiology GA 943XI UT WOS:000230388500098 ER PT J AU Vagin, O Turdikulova, S Sachs, G AF Vagin, O Turdikulova, S Sachs, G TI N-linked glycosylation provides apical sorting information to the gastric H,K-ATPase beta and to the Na,KATPase beta(2) subunit. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 94 BP 42A EP 42A PG 1 WC Physiology SC Physiology GA 943XI UT WOS:000230388500102 ER PT J AU Arystarkhova, E Pascoa, JL Sweadner, KJ AF Arystarkhova, E Pascoa, JL Sweadner, KJ TI Deletion of its COOH-terminal exon results in retention of gamma b in the endoplasmic reticulum and acceleration of cell growth SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 108 BP 48A EP 48A PG 1 WC Physiology SC Physiology GA 943XI UT WOS:000230388500116 ER PT J AU Donnet, C Sweadner, K AF Donnet, C Sweadner, K TI Endogenous FXYD5 and transfected FXYD1 copurify with Na,K-ATPase in HEK293 cells. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 59th annual Meeting of the Society-of-General-Physiologists CY SEP 06-11, 2005 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Membrane Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2005 VL 126 IS 1 MA 112 BP 49A EP 50A PG 2 WC Physiology SC Physiology GA 943XI UT WOS:000230388500120 ER PT J AU Ring, D Patterson, JD Levitz, S Wang, C Jupiter, JB AF Ring, D Patterson, JD Levitz, S Wang, C Jupiter, JB TI Both scanning plane and observer affect measurements of scaphoid deformity SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE scaphoid fracture; malunion; deformity; computed tomography; measurements ID COMPUTED-TOMOGRAPHY; MALUNION; RELIABILITY AB Purpose: The influence of angular deformity of the scaphoid on wrist function and arthrosis is debated and the reliability of the described quantitative measurements of deformity has been questioned. We hypothesized that the inherent imprecision with which computed tomography scanning planes are selected introduces another source of variability in measurements of scaphoid deformity, further diminishing their reliability. Methods: Sagittal plane images of 15 computed tomograms of normal scaphoids were evaluated in 3 different reconstruction planes. Four observers measured the lateral intrascaphoid angle, the dorsal cortical angle, and the height-to-length ratio of the 45 images in random order and then measured them again in a distinct random order 2 weeks later. The variability of each observer's measurements (intraobserver reliability) was evaluated with Pearson correlation coefficients. The agreement of the measurements made by the 4 observers (interobserver reliability) and the agreement of the measurements of the same bone in different reconstruction planes (interplane reliability) were evaluated using interclass correlation coefficients. Results: The intraobserver reliability was poor for 27 of 36 comparisons. The interobserver reliability of the dorsal cortical angle and the intrascaphoid angle was poor for all reconstruction planes. The interobserver reliability of the height-to-length ratio was good for 2 planes and poor for the third plane. The interplane reliability was poor for 7 of 12 comparisons, with no single measurement technique remaining consistent for all observers across reconstruction planes. Conclusions: Quantitative measurements of scaphoid deformity have very limited reliability for individual observers, between different observers, and depending on the plane in which the image of the scaphoid is produced. Even the most reliable measure of deformity (height-to-length ratio) was not consistent between reconstruction planes. Unless more reliable scanning and measurement techniques are developed ideas about the effect of scaphoid deformity on wrist function will remain to a large degree speculative. C1 Massachusetts Gen Hosp, Yawkee Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Orthopaed Residency Program, Boston, MA 02215 USA. Harvard Univ, Combined Orthopaed Residency Program, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 10 TC 18 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2005 VL 30A IS 4 BP 696 EP 701 DI 10.1016/j.jhsa.2005.03.001 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 949RB UT WOS:000230804700008 PM 16039360 ER PT J AU Cohen, GB Kaur, A Johnson, RP AF Cohen, GB Kaur, A Johnson, RP TI Isolation of viable antigen-specific CD4 T cells by CD40L surface trapping SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CD4 T cell; CD154; CD40L; rhesus macaque ID IN-VIVO; RHESUS-MONKEYS; MEMORY; LYMPHOCYTES; EXPRESSION; VIRUS; NAIVE; ACTIVATION; EFFECTOR; INFECTION AB A number of techniques have recently been developed for the identification of antigen-specific cells, yet the ability of these techniques to identify all subclasses of memory T cells has often been overlooked. Here we describe a novel approach for the isolation of live antigen-specific CD4 T cells using CD40L and CD69 surface staining and demonstrate its utility for isolating antigen-specific rhesus macaque CD4 T cells. Critical to the success of the technique was staining for CD40L concurrent with antigen stimulation. Isolation of CD4 T cells based on CD40L/CD69 surface marker upregulation identified both effector and central memory CD4 T cells. In contrast, the majority of central memory CD4 T cells did not secrete TNF alpha or IFN gamma and thus would not be identified by techniques based on their secretion. The methodology described here therefore complements existing approaches for isolating viable antigen-specific CD4 T cells, opens new avenues for investigating human diseases in nonhuman primate animal models and may prove beneficial in instances where the induced response is largely T cell central memory restricted. (c) 2005 Elsevier B.V. All rights reserved. C1 Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA. Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02454 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Immunol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Cohen, GB (reprint author), Brandeis Univ, Dept Biochem, 415 South St, Waltham, MA 02454 USA. EM gcohen@brandeis.edu; paul_johnson@hms.harvard.edu FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI45314, AI43890] NR 50 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL PY 2005 VL 302 IS 1-2 BP 103 EP 115 DI 10.1016/j.jim.2005.05.002 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 959AZ UT WOS:000231490600010 PM 15993419 ER PT J AU Domenig, C Sanchez-Fueyo, A Kurtz, J Alexopoulos, SP Mariat, C Sykes, M Strom, TB Zheng, XX AF Domenig, C Sanchez-Fueyo, A Kurtz, J Alexopoulos, SP Mariat, C Sykes, M Strom, TB Zheng, XX TI Roles of deletion and regulation in creating mixed chimerism and allograft tolerance using a nonlymphoablative irradiation-free protocol SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; T-CELL TOLERANCE; NONLETHAL PREPARATIVE REGIMEN; DONOR-SPECIFIC TOLERANCE; COSTIMULATORY BLOCKADE; THYMIC DELETION; INDUCTION; MECHANISMS; ENGRAFTMENT; REJECTION AB The induction of mixed chimerism (MC) is a powerful and effective means to achieve transplantation tolerance in rodent models. Host conditioning with irradiation or cytotoxic drugs has been used in many protocols for chimeric induction across allogeneic barriers. The deletion of alloreactive T cell clones has been described as the main mechanism responsible for the induction of a stable MC. In this study, we demonstrate that a stable MC and skin allograft tolerance can be established across MHC barriers by a noncytotoxic, irradiation-free approach using costimulation blockade plus rapamycin treatment. By using an adoptive transfer model of skin allograft and using specific V beta TCR probes, we demonstrated that deletion of donor-reactive cytopathic T cell clones is indeed profound in tolerant hosts. Nonetheless, the challenge of tolerant mixed chimeras with 5 million mononuclear leukocytes (MNL) from naive syngeneic mice was neither able to abolish the stable MC nor to trigger skin allograft rejection, a hallmark of peripheral, not central tolerance. Furthermore, in an adoptive transfer model, MNLs harvested from tolerant hosts significantly inhibited the capacity of naive MNLs to reject same donor, but not third-party, skin allografts. Moreover, when we transplanted skin allografts from stable tolerant chimeras onto syngeneic immune-incompetent mice, graft-infiltrating T cells migrated from the graft site, expanded in the new host, and protected allografts from acute rejection by naive syngeneic MNLs. In this model, both deletional and immunoregulatory mechanisms are active during the induction and/or maintenance of allograft tolerance through creation of MC using a potentially clinically applicable regimen. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplantat Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplantat Res Ctr, Boston, MA 02215 USA. EM tstrom@bidmc.harvard.edu; xzheng@bidmc.harvard.edu NR 48 TC 55 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2005 VL 175 IS 1 BP 51 EP 60 PG 10 WC Immunology SC Immunology GA 939CW UT WOS:000230050900009 PM 15972631 ER PT J AU Feng, HP Zhang, D Palliser, D Zhu, PC Cai, SH Schlesinger, A Maliszewski, L Lieberman, J AF Feng, HP Zhang, D Palliser, D Zhu, PC Cai, SH Schlesinger, A Maliszewski, L Lieberman, J TI Listeria-infected myeloid dendritic cells produce IFN-beta priming T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; IMMUNE-RESPONSES; I INTERFERON; PROTECTIVE IMMUNITY; GENE-EXPRESSION; BACTERIAL PEPTIDOGLYCAN; MONOCYTOGENES VACCINE; POSITIVE FEEDBACK; GAG PROTEIN; INDUCTION AB The intracellular bacterium Listeria monocytogenes infects dendritic cells (DC) and other APCs and induces potent cell-mediated protective immunity. However, heat-killed bacteria fail to do so. This study explored whether DC differentially respond to live and killed Listeria and how this affects T cell activation. To control for bacterial number, a replication-deficient strain, Lmdd, defective in D-alanine biosynthesis, was used. We found that DC internalize both live and heat-killed Lmdd and similarly up-regulate the expression of costimulatory molecules, a necessary step for T cell activation. However, only live Lmdd-infected DC stimulate T cells to express the early activation marker CD69 and enhance T cell activation upon TCR engagement. Infection with live, but not heat-killed, Lmdd induces myeloid DC to secrete copious amounts of IFN-beta, which requires bacterial cytosolic invasion. Exposure to high concentrations of IFN-beta sensitizes naive T cells for Ag-dependent activation. C1 CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), CBR, Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NHLBI NIH HHS [T32HL066987]; NIAID NIH HHS [AI056922] NR 54 TC 51 Z9 53 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 JUL 1 PY 2005 VL 175 IS 1 BP 421 EP 432 PG 12 WC Immunology SC Immunology GA 939CW UT WOS:000230050900054 PM 15972676 ER PT J AU Nath, N Giri, S Prasad, R Salem, ML Singh, AK Singh, I AF Nath, N Giri, S Prasad, R Salem, ML Singh, AK Singh, I TI 5-Aminoimidazole-4-carboxamide ribonucleoside: A novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELL-PERMEABLE ACTIVATOR; MULTIPLE-SCLEROSIS; T-CELLS; TRANSCRIPTION FACTOR; NERVOUS-SYSTEM; AICA-RIBOSIDE; ACADESINE; TOLERANCE AB Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is a Th1-mediated inflammatory demyelinating disease of the CNS. AMP-activated protein kinase was reported recently to have anti-inflammatory activities by negatively regulating NF-kappa B signaling. In this study, we investigated the prophylactic and therapeutic efficacy of an AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), in active and passive EAE induced by active immunization with PLP139-151 or MOG(35-55) and in adoptive transfer of PLP139-151-sensitized T cells, respectively. In vivo treatment with AICAR exerted both prophylactic and therapeutic effects on EAE, attenuating the severity of clinical disease. The anti-inflammatory effects of AICAR were associated with the inhibition of the Ag-specific recall responses and inhibition of the Th1-type cytokines IFN-gamma and TNF-alpha, whereas it induced the production of Th2 cytokines IL-4 and IL-10. Treatment of PLP139-151-specific T cells in vitro with AICAR decreased their expression of T-bet in response to IL-12, a Th1 transcription factor, whereas in response to IL-4, it induced the expression and phosphorylation of Th2 transcription factors GATA3 and STAT6, respectively. Moreover, treatment of APCs in vitro with AICAR inhibited their capability to present the proteolipid protein peptide to PLP139-151-specific T cells. In an irrelevant Th1-mediated, OT-2 TCR transgenic mouse model, AICAR impaired in vivo Ag-specific expansion of CD4(+) T cells. Together, these findings show for the first time that AICAR is a novel immunomodulator with promising beneficial effects for the treatment of multiple sclerosis and other Th1-mediated inflammatory diseases. C1 Med Univ S Carolina, Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Childrens Res Inst, Dept Pediat, 173 Ashley Ave,Suite 505, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 49 TC 89 Z9 92 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2005 VL 175 IS 1 BP 566 EP 574 PG 9 WC Immunology SC Immunology GA 939CW UT WOS:000230050900071 PM 15972693 ER PT J AU Astner, S Gonzalez, E Doukas, A Rius-Diaz, F Gonzalez, S AF Astner, S Gonzalez, E Doukas, A Rius-Diaz, F Gonzalez, S TI Non-invasive evaluation or irritant and allergic contact dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Wellman Ctr Photomed, Dept Dermatol, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Contact Dermatol Serv, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2005 VL 125 IS 1 MA 916 BP A3 EP A3 PG 1 WC Dermatology SC Dermatology GA 943GR UT WOS:000230342000035 ER PT J AU Miller, JD Hogan, H Kogan, S Greenes, R Ting-Lee, M Kvedar, J Christian, R AF Miller, JD Hogan, H Kogan, S Greenes, R Ting-Lee, M Kvedar, J Christian, R TI Using teledermatology in the management of post-op breast surgery patients to decrease length of stay: a pilot study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2005 VL 125 IS 1 MA 941 BP A7 EP A7 PG 1 WC Dermatology SC Dermatology GA 943GR UT WOS:000230342000062 ER PT J AU Werth, VP Strober, BE Connolly, M Korman, N Greenstein, D Fantasia, J Kalish, R Anhalt, G AF Werth, VP Strober, BE Connolly, M Korman, N Greenstein, D Fantasia, J Kalish, R Anhalt, G TI An open-label phase I clinical study to assess the safety of PI-0824 in patients with pemphigus vulgaris SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. CUNY, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. E Coast Clin Res, Salisbury, MA USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2005 VL 125 IS 1 MA 930 BP A5 EP A5 PG 1 WC Dermatology SC Dermatology GA 943GR UT WOS:000230342000048 ER PT J AU Fu, YC Luo, NL Klein, RL Garvey, WT AF Fu, YC Luo, NL Klein, RL Garvey, WT TI Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE obesity/diabetes; gene expression; adipocytokine; glucose; lipid metabolism ID BINDING-PROTEIN-ALPHA; PIMA INDIAN POPULATION; FATTY-ACID OXIDATION; 3T3-L1 ADIPOCYTES; ADIPOSE CONVERSION; GENE-EXPRESSION; PPAR-GAMMA; DIFFERENT MECHANISMS; HORMONE ADIPONECTIN; ENERGY HOMEOSTASIS AB Adiponectin is secreted from adipocytes, and low circulating levels have been epidemiologically associated with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate whether adiponectin could exert autocrine effects in adipocytes, we expressed the adiponectin gene in 3T3-L1 fibroblasts. We observed that 3T3-L1 fibroblasts expressing adiponectin have a fast growth phase and reach confluence more rapidly compared with control cells or LacZ-transduced cells. Furthermore, cells with overexpressed adiponectin were observed to differentiate into adipocytes more rapidly, and during adipogenesis, they exhibited more prolonged and robust gene expression for related transcriptional factors, CCAAT/enhancer binding protein alpha (C/EBP2), peroxisome proliferator-activated receptor gamma ( PPAR gamma), and adipocyte determination and differentiation factor 1/stero/regulatory element binding protein 1c ( ADD1/SREBP1c) and earlier suppression of PPAR gamma coactivator-1 alpha (PGC-1 alpha). In fully differentiated adipocytes, adiponectin-overexpressing cells accumulated more and larger lipid droplets compared with control cells. Also, adiponectin increased insulin's ability to maximally stimulate glucose uptake by 78% through increased glucose transporter 4 ( GLUT4) gene expression and increased GLUT4 recruitment to the plasma membrane. These data suggest a new role for adiponectin as an autocrine factor in adipose tissues: promoting cell proliferation and differentiation from preadipocytes into adipocytes, augmenting programmed gene expression responsible for adipogenesis, and increasing lipid content and insulin responsiveness of the glucose transport system in adipocytes. - Fu, Y., N. Luo, R. L. Klein, and W. T. Garvey. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Charleston VA Med Ctr, Charleston, SC 29425 USA. Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. EM yfu@uab.edu FU NHLBI NIH HHS [P01-HL-55782]; NIDDK NIH HHS [DK-38764] NR 53 TC 258 Z9 275 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2005 VL 46 IS 7 BP 1369 EP 1379 DI 10.1194/jlr.M400373-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XA UT WOS:000229741700003 PM 15834118 ER PT J AU Polyak, K Hu, M AF Polyak, K Hu, M TI Do myoepithelial cells hold the key for breast tumor progression? SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE myoepithelium; tumor progression; DCIS (ductal carcinoma in situ); paracrine factor; SAGE (serial analysis of gene expression) ID CARCINOMA IN-SITU; MAMMARY STEM/PROGENITOR CELLS; CONTRIBUTE ONCOGENIC SIGNALS; DUCTAL CARCINOMA; EPITHELIAL-CELLS; GENE-EXPRESSION; STROMAL CELLS; CANCER-CELLS; FIBROBLASTS; GLAND AB Mammary myoepithelial cells have been a neglected facet of breast cancer biology, largely ignored since they have been considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge of stem cell biology and the cellular microenvironment has been increasing, myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis whether myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and that myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for regulation of cell cycle progression, establishing epithelial cell polarity, and inhibiting cell migration and invasion. Based on these functions, normal mammary myoepithelial cells have been called "natural tumor suppressors." However, during tumor progression myoepithelial cells seem to loose these properties, and eventually this cell population diminishes as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu FU NCI NIH HHS [CA94074-03, P50 CA89393-05] NR 92 TC 94 Z9 95 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JUL PY 2005 VL 10 IS 3 BP 231 EP 247 DI 10.1007/s10911-005-9584-6 PG 17 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 052HK UT WOS:000238224600005 PM 16807803 ER PT J AU Leaf, A AF Leaf, A TI Potential human benefits of long-chain polyunsaturated n-3 fatty acids - Alexander Leaf, guest editor - Foreword SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02138 USA. RP Leaf, A (reprint author), Harvard Univ, Sch Med, Dept Med, 149,13th St, Boston, MA 02138 USA. EM aleaf@partners.org 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 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL PY 2005 VL 206 IS 2 BP 73 EP 73 DI 10.1007/s00232-005-0797-9 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 003YC UT WOS:000234718200001 ER PT J AU Leaf, A Xiao, YF Kang, JX Billman, GE AF Leaf, A Xiao, YF Kang, JX Billman, GE TI Membrane effects of the n-3 fish oil fatty acids, which prevent fatal ventricular arrhythmias SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article ID RAT CARDIAC MYOCYTES; SODIUM-CHANNEL INACTIVATION; NA+ CHANNELS; SUDDEN-DEATH; LONG-CHAIN; FIBRILLATION; ISCHEMIA; INFARCTION; CURRENTS; STATES AB Fish oil fatty acids are known to exert beneficial effects on the heart and vascular systems. We have studied the membrane effects on ion channel conductance by the n-3 fish oil fatty acids that account for these beneficial effects. We have confirmed that these fatty acids prevent fatal cardiac arrhythmias in a reliable dog model of sudden cardiac death. This finding was followed by experiments indicating that the n-3 fatty acids electrically stabilize heart cells and do so largely through modulation of the fast voltage-dependent Na+ currents and the L-type Ca2+ channels in a manner, which makes the heart cells resistant to arrhythmias. Others and we have demonstrated that these membrane effects on the heart can prevent fatal cardiac arrhythimas in humans. C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ohio State Univ, Dept Physiol & Cell Biol, Columbus, OH 43210 USA. RP Leaf, A (reprint author), Harvard Univ, Sch Med, Dept Med, 149,13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org RI Billman, George/E-2758-2011 NR 34 TC 57 Z9 62 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 EI 1432-1424 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL PY 2005 VL 206 IS 2 BP 129 EP 139 DI 10.1007/s00232-005-0789-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 003YC UT WOS:000234718200006 PM 16456723 ER PT J AU Xiao, YF Sigg, DC Leaf, A AF Xiao, YF Sigg, DC Leaf, A TI The antiarrhythmic effect of n-3 polyunsaturated fatty acids: Modulation of cardiac ion channels as a potential mechanism SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE cardiac arrhythmia; eicosapentaenoic acid; docosahexaenoic acid; hyperpolarization activated cyclic-nucleotide-modulated channel mutation ID RAT VENTRICULAR MYOCYTES; GISSI-PREVENZIONE TRIAL; CORONARY-HEART-DISEASE; NA+ CHANNELS; LONG-CHAIN; SODIUM-CHANNEL; FISH-OIL; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; GRAMICIDIN CHANNELS AB Sudden cardiac death remains one of the most serious medical challenges in Western countries. Increasing evidence in recent years has demonstrated that the n-3 polyunsaturated fatty acids (PUFAs) can prevent fatal ventricular arrhythmias in experimental animals and probably in humans. Dietary supplement of fish oils or intravenous infusion of the n-3 PUFAs prevents ventricular fibrillation caused by ischemia/reperfusion. Similar antiarrhythmic effects of these fatty acids are also observed in cultured mammalian cardiomyocytes. Based on clinical observations and experimental studies in vitro and in vivo, several mechanisms have been postulated for the antiarrhythmic effect of the n-3 PUFAs. The data from our laboratory and others have shown that the n-3 PUFAs are able to affect the activities of cardiac ion channels. The modulation of channel activities, especially voltage-gated Na+ and L-type Ca2+ channels, by the n-3 fatty acids may explain, at least partially, the antiarrhythmic action. It is not clear, however, whether one or more than one mechanism involves the beneficial effect of the n-3 PUFAs on the heart. This article summarizes our recent studies on the specific effects of the n-3 PUFAs on cardiac ion channels. In addition, the effect of the n-3 PUFAs on the human hyperpolarization-activated cyclic-nucleotide-modulated channel is presented. C1 Medtronic Inc, Cardiac Rhythm Management, Minneapolis, MN 55432 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. RP Xiao, YF (reprint author), Medtronic Inc, Cardiac Rhythm Management, Minneapolis, MN 55432 USA. EM yong-fu.xiao@medtronic.com FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 65 TC 76 Z9 82 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL PY 2005 VL 206 IS 2 BP 141 EP 154 DI 10.1007/S00232-005-0786-Z PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 003YC UT WOS:000234718200007 PM 16456724 ER PT J AU Kang, JX AF Kang, JX TI From fat to fat-1: A tale of omega-3 fatty acids SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article ID ADENOVIRAL GENE-TRANSFER; ACID DESATURASE; CARDIOVASCULAR-DISEASE; NEURONAL APOPTOSIS; HEALTH; CELLS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM jxkang@partners.org NR 21 TC 32 Z9 39 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL PY 2005 VL 206 IS 2 BP 165 EP 172 DI 10.1007/s00232-005-0790-3 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 003YC UT WOS:000234718200009 PM 16456726 ER PT J AU Prasad, R Giri, S Nath, N Singh, I Singh, AK AF Prasad, R Giri, S Nath, N Singh, I Singh, AK TI Inhibition of phosphoinositide 3 kinase-Akt (protein kinase B)-nuclear factor-kappa B pathway by lovastatin limits endothelial-monocyte cell interaction SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE endothelial; experimental autoimmune encephalomyelitis; lovastatin; monocytes; nuclear factor-kappa B; PI3-kinase ID NITRIC-OXIDE SYNTHASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RHO-FAMILY GTPASES; PHOSPHATIDYLINOSITOL 3-KINASE; ADHESION MOLECULE-1; E-SELECTIN; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); REDUCTASE INHIBITOR; MULTIPLE-SCLEROSIS; LEWIS RATS AB Integrity of the blood-brain barrier is essential for the normal functioning of CNS. Its disruption contributes to the pathobiology of various inflammatory neurodegenerative disorders. We have shown that the HMG-CoA reductase inhibitor (lovastatin) attenuated experimental autoimmune encephalomyelitis (EAE, an inflammatory disease of CNS) in rodents by inhibiting the infiltration of mononuclear cells into the CNS. Here, using an in vitro system, we report that lovastatin inhibits endothelial-monocyte cell interaction by down-regulating the expression of vascular cell adhesion molecule-1 and E-selectin by inhibiting the phosphoinositide 3 kinase (PI3-kinase)/protein kinase B (Akt)/nuclear factor-kappa B (NF-kappa B) pathway in endothelial cells. It inhibits tumor necrosis factor alpha (TNF alpha)-induced PI3-kinase, Akt and NF-kappa B activation in these cells. Co-transfection of constitutively active forms of PI3-kinase and Akt reversed the lovastatin-mediated inhibition of TNF alpha-induced adhesion, as well as activation of NF-kappa B, indicating the involvement of the PI3-kinase/Akt pathway in the interaction of adhesion molecules and the process of adhesion. This study reports that lovastatin down-regulates the pathway affecting the expression and interaction of adhesion molecules on endothelial cells, which in turn restricts the migration and infiltration of mononuclear cells thereby attenuating the pathogenesis of inflammatory diseases. C1 Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Singh, I (reprint author), Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS 37766, NS-34741, NS-40144, NS-40810] NR 60 TC 41 Z9 45 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2005 VL 94 IS 1 BP 204 EP 214 DI 10.1111/j.1471-4159.2005.03182.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 934JO UT WOS:000229705300020 PM 15953363 ER PT J AU Rostasy, K Monti, L Lipton, SA Hedreen, JC Gonzalez, RG Navia, BA AF Rostasy, K Monti, L Lipton, SA Hedreen, JC Gonzalez, RG Navia, BA TI HIV leucoencephalopathy and TNF alpha expression in neurones SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-DEMENTIA-COMPLEX; NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; TAT PROTEIN; NEOCORTICAL DAMAGE; MESSENGER-RNA; KAPPA-B; INFECTION; APOPTOSIS AB Background: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor alpha (TNF alpha), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. Objective: To examine the clinical/neuroradiological features of HIVL and the expression of TNF alpha in HIVL. Methods: Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry. Results: Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNF alpha was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNF alpha expression in neurones of the frontal cortex and basal ganglia. Conclusion: This study provides the first demonstration of staining for TNF alpha in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNF alpha. C1 Tufts Univ New England Med Ctr, Tufts Neurol Program, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. Univ Gottingen, D-37073 Gottingen, Germany. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02111 USA. Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA. RP Navia, BA (reprint author), Tufts New England Med Ctr, Psychiat Res Labs, 75 Kneeland St, Boston, MA 02111 USA. EM BNavia@tufts-nemc.org FU NICHD NIH HHS [P01 HD 29587]; NINDS NIH HHS [R01 NS 36524, F32 NS10867] NR 47 TC 10 Z9 11 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2005 VL 76 IS 7 BP 960 EP 964 DI 10.1136/jnnp.2004.036889 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 940IL UT WOS:000230137200012 PM 15965202 ER PT J AU Domnitz, SB Robbins, EM Hoang, AW Garcia-Alloza, M Hyman, BT Rebeck, GW Greenberg, SM Bacskai, BJ Frosch, MP AF Domnitz, SB Robbins, EM Hoang, AW Garcia-Alloza, M Hyman, BT Rebeck, GW Greenberg, SM Bacskai, BJ Frosch, MP TI Progression of cerebral amyloid angiopathy in transgenic mouse models of Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer; amyloid-beta; angiopathy; mouse; multiphoton; transgenic; vascular ID PRECURSOR PROTEIN; MULTIPHOTON MICROSCOPY; SPONTANEOUS HEMORRHAGE; NEURONAL LOSS; MICE; MUTANT; DEPOSITION; MATRIX-METALLOPROTEINASE-9; INFARCTION; DEFICITS AB Cerebral amyloid angiopathy (CAA), the deposition of B-amyloid (AB) in cerebral vessels, has been implicated as a common cause of hemorrhagic stroke and other forms of vascular disease. CAA is also a frequent concomitant of Alzheimer disease (AD). While the long-term consequences of CAA are well recognized from clinical and pathologic studies, numerous questions remain unanswered regarding the progression of the disease. Examination of CAA in traditional histologic sections does not easily allow for characterization of CAA, particularly in leptomeningeal vessels. In order to approach this topic, we used low magnification imaging of intact, postmortem brains from transgenic mouse models of AD-like pathology to define the spatial and temporal characteristics of CAA in leptomeningeal vessels. Imaging of brains from 10- to 26-month-old animals demonstrated a stereotypical pattern to the development of CAA, with vessels over the dorsal surface of the brain showing an anterior-to-posterior and large-to-small vessel gradient of involvement. High magnification imaging revealed that CAA deposition began with a banding pattern determined by the organization of the vascular smooth muscle cells. Further analysis of the pattern of amyloid deposits showed shrinkage and disappearance of the gaps between clusters of amyloid bands, gradually reaching a confluent pattern. These data led to a classification system to describe the severity of CAA deposition and demonstrate the potential of using intact brains to generate maps defining the progression and kinetics of CAA. This approach should lead to more informed analysis of the consequences of evolving therapeutic options for AD on this related form of vascular pathology. C1 Massachusetts Gen Hosp, Massachussets Gen Inst Neurodegenerat Dis, Dept Neurol, Alzheimer Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Georgetown Univ, Dept Neurosci, Washington, DC USA. RP Frosch, MP (reprint author), B114-2700,MGH,114 16th St, Hillsborough 02129, North Ireland. EM matthew_frosch@hms.harvard.edu OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG020570, AG08487, AG021084]; NIBIB NIH HHS [EB000768] NR 31 TC 38 Z9 38 U1 0 U2 2 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 JUL PY 2005 VL 64 IS 7 BP 588 EP 594 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 945IL UT WOS:000230496100004 PM 16042310 ER PT J AU Kass, RE Ventura, V Brown, EN AF Kass, RE Ventura, V Brown, EN TI Statistical issues in the analysis of neuronal data SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID TRAIN DATA-ANALYSIS; STOCHASTIC POINT PROCESSES; HIPPOCAMPAL PLACE CELLS; SPIKE-TRAIN; CORTICAL-NEURONS; SINGLE-NEURON; 2 CULTURES; POPULATION; CORTEX; MODELS AB Analysis of data from neurophysiological investigations can be challenging. Particularly when experiments involve dynamics of neuronal response, scientific inference can become subtle and some statistical methods may make much more efficient use of the data than others. This article reviews well-established statistical principles, which provide useful guidance, and argues that good statistical practice can substantially enhance results. Recent work on estimation of firing rate, population coding, and time-varying correlation provides improvements in experimental sensitivity equivalent to large increases in the number of neurons examined. Modern nonparametric methods are applicable to data from repeated trials. Many within-trial analyses based on a Poisson assumption can be extended to non-Poisson data. New methods have made it possible to track changes in receptive fields, and to study trial-to-trial variation, with modest amounts of data. C1 Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Res Lab, Boston, MA 02114 USA. RP Ventura, V (reprint author), Carnegie Mellon Univ, Dept Stat, 5000 Forbes Ave,Baker Hall 132, Pittsburgh, PA 15213 USA. EM vventura@stat.cmu.edu FU NIDA NIH HHS [DA-015664]; NIMH NIH HHS [MH-59733, MH-61637, MH-64537, R25 MH-66410] NR 81 TC 164 Z9 164 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2005 VL 94 IS 1 BP 8 EP 25 DI 10.1152/jn.00648.2004 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 940HY UT WOS:000230135500004 PM 15985692 ER PT J AU Merfeld, DM Park, S Gianna-Poulin, C Black, FO Wood, S AF Merfeld, DM Park, S Gianna-Poulin, C Black, FO Wood, S TI Vestibular perception and action employ qualitatively different mechanisms. I. Frequency response of VOR and perceptual responses during Translation and Tilt SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID EYE-MOVEMENT RESPONSES; GRAVITO-INERTIAL CUES; HUMAN VESTIBULOOCULAR REFLEX; OTOLITH-OCULAR REFLEXES; VERTICAL AXIS ROTATION; SEARCH COIL SIGNALS; LINEAR ACCELERATION; SQUIRREL-MONKEY; ECCENTRIC ROTATION; SPATIAL ORIENTATION AB To investigate the neural mechanisms that humans use to process the ambiguous force measured by the otolith organs, we measured vestibuloocular reflexes (VORs) and perceptions of tilt and translation. One primary goal was to determine if the same, or different, mechanisms contribute to vestibular perception and action. We used motion paradigms that provided identical sinusoidal inter-aural otolith cues across a broad frequency range. We accomplished this by sinusoidally tilting (20 degrees, 0.005-0.7 Hz) subjects in roll about an earth-horizontal, head-centered, rotation axis ("Tilt") or sinusoidally accelerating (3.3 m/s(2), 0.005-0.7 Hz) subjects along their inter-aural axis ("Translation"). While identical inter-aural otolith cues were provided by these motion paradigms, the canal cues were substantially different because roll rotations were present during Tilt but not during Translation. We found that perception was dependent on canal cues because the reported perceptions of both roll tilt and inter- aural translation were substantially different during Translation and Tilt. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs at frequencies >0.2 Hz during both Translation and Tilt. These responses were dependent on otolith cues and match simple filtering predictions that translational VORs include contributions via simple high-pass filtering of otolith cues. More generally, these findings demonstrate that internal models govern human vestibular "perception" across a broad range of frequencies and that simple high-pass filters contribute to human horizontal translational VORs ("action") at frequencies above similar to 0.2 Hz. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Legacy Clin Res & Technol Ctr, Neurotol Res, Portland, OR USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Room 421,243 Charles St, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu RI Park, Sukyung/C-1628-2011 FU NIDCD NIH HHS [DC-00205, DC-004158] NR 101 TC 95 Z9 97 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2005 VL 94 IS 1 BP 186 EP 198 DI 10.1152/jn.00904.2004 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 940HY UT WOS:000230135500019 PM 15728767 ER PT J AU Merfeld, DM Park, S Poulin, CG Black, FO Wood, S AF Merfeld, DM Park, S Poulin, CG Black, FO Wood, S TI Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt&Translation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GRAVITO-INERTIAL CUES; OTOLITH-OCULAR REFLEXES; VESTIBULOOCULAR REFLEX; SQUIRREL-MONKEY; ECCENTRIC ROTATION; EYE-MOVEMENTS; LINEAR ACCELERATION; SPATIAL ORIENTATION; SEMICIRCULAR CANALS; RHESUS-MONKEYS AB To compare and contrast the neural mechanisms that contribute to vestibular perception and action, we measured vestibuloocular reflexes (VOR) and perceptions of tilt and translation. We took advantage of the well-known ambiguity that the otolith organs respond to both linear acceleration and tilt with respect to gravity and investigated the mechanisms by which this ambiguity is resolved. A new motion paradigm that combined roll tilt with inter-aural translation ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted but with their ears above or below the rotation axis. This paradigm provided sinusoidal roll canal cues that were the same across trials while providing otolith cues that varied linearly with ear position relative to the earth-horizontal rotation axis. We found that perceived tilt and translation depended on canal cues, with substantial roll tilt and inter-aural translation perceptions reported even when the otolith organs measured no inter-aural force. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs that varied linearly with radius; a minimal response was measured when the otolith organs transduced little or no inter-aural force. Hence, the horizontal translational VOR was dependent on otolith cues but independent of canal cues. These findings match predictions that translational VORs are elicited by simple filtering of otolith signals. We conclude that internal models govern human perception of tilt and translation at 0.8 Hz and that high-pass filtering governs the human translational VOR at this same frequency. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Legacy Clin Res & Technol Ctr, Neurotol Res, Portland, OR USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Room 421,243 Charles St, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu RI Park, Sukyung/C-1628-2011 FU NIDCD NIH HHS [DC-004158, DC-00205] NR 43 TC 77 Z9 78 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2005 VL 94 IS 1 BP 199 EP 205 DI 10.1152/jn.00905.2004 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 940HY UT WOS:000230135500020 PM 15730979 ER PT J AU Cedolin, L Delgutte, B AF Cedolin, L Delgutte, B TI Pitch of complex tones: Rate-place and interspike interval representations in the auditory nerve SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STEADY-STATE VOWELS; GUINEA-PIG; FUNDAMENTAL FREQUENCIES; LEVEL DISCRIMINATION; UNRESOLVED HARMONICS; DOMINANCE REGION; EPTESICUS-FUSCUS; COCHLEAR-NERVE; UNITARY MODEL; RIPPLED NOISE AB Harmonic complex tones elicit a pitch sensation at their fundamental frequency (F0), even when their spectrum contains no energy at F0, a phenomenon known as "pitch of the missing fundamental." The strength of this pitch percept depends upon the degree to which individual harmonics are spaced sufficiently apart to be "resolved" by the mechanical frequency analysis in the cochlea. We investigated the resolvability of harmonics of missing-fundamental complex tones in the auditory nerve (AN) of anesthetized cats at low and moderate stimulus levels and compared the effectiveness of two representations of pitch over a much wider range of F0s (110-3,520 Hz) than in previous studies. We found that individual harmonics are increasingly well resolved in rate responses of AN fibers as the characteristic frequency (CF) increases. We obtained rate-based estimates of pitch dependent upon harmonic resolvability by matching harmonic templates to profiles of average discharge rate against CF. These estimates were most accurate for F0s above 400-500 Hz, where harmonics were sufficiently resolved. We also derived pitch estimates from all-order interspike-interval distributions, pooled over our entire sample of fibers. Such interval-based pitch estimates, which are dependent on phase-locking to the harmonics, were accurate for F0s below 1,300 Hz, consistent with the upper limit of the pitch of the missing fundamental in humans. The two pitch representations are complementary with respect to the F0 range over which they are effective; however, neither is entirely satisfactory in accounting for human psychophysical data. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM cedro@mit.edu OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [T32 DC000038, R01 DC002258, R01 DC-02258, P30 DC-05209, P30 DC005209] NR 93 TC 48 Z9 48 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2005 VL 94 IS 1 BP 347 EP 362 DI 10.1152/jn.01114.2004 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 940HY UT WOS:000230135500034 PM 15788522 ER PT J AU MacNeill, BD Bouma, BE Yabushita, H Jang, LK Tearney, GJ AF MacNeill, BD Bouma, BE Yabushita, H Jang, LK Tearney, GJ TI Intravascular optical coherence tomography: Cellular imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID CORONARY ATHEROSCLEROTIC PLAQUES; MONOCYTE-DERIVED MACROPHAGES; TISSUE FACTOR; UNSTABLE ANGINA; ARTERY-DISEASE; RUPTURE; THROMBOSIS; DEATH; INFLAMMATION; EXPRESSION AB The vast majority of acute coronary events are attributed to rupture or erosion of high-risk or vulnerable plaques. Novel imaging techniques are being actively sought that can detect quiescent vulnerable features within coronary plaque and thereby identify populations at risk, monitor plaque progression, and target therapy appropriately. Optical coherence tomography is an intravascular imaging modality capable of detecting and characterizing coronary plaque in vivo. Recently, optical coherence tomography quantification of macrophage infiltration within atherosclerotic plaque ex vivo was demonstrated. Application of this technique to clinical practice yields a hybrid image incorporating plaque morphology with a measure of biologic activity. In a recently conducted clinical study assessing macrophage distributions in patients, evidence supporting both the vulnerable plaque model and the hypothesis of multifocal inflammatory risk, linked by the common thread of increased macrophage infiltration, has been found. These results suggest that elevated multifocal coronary macrophage content, present both in culprit lesions and at remote sites, serves as a background for heightened risk. Superimposed on this inflammatory background, local increases in macrophage content, particularly at the cap surface and at areas at high risk for rupture, further promote the instability of individual lesions. C1 Massachusetts Gen Hosp, Lab Photomed, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kinki Univ, Sch Med, Dept Cardiol, Osaka 589, Japan. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Lab Photomed, Div Cardiol, BAR 703, Boston, MA 02114 USA. EM gtearney@partner.org NR 30 TC 21 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUL-AUG PY 2005 VL 12 IS 4 BP 460 EP 465 DI 10.1016/j.nuclcard.2005.05.013 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 952HC UT WOS:000230993600013 PM 16084435 ER PT J AU Dodson, TB AF Dodson, TB TI Is there a role for reconstructive techniques to prevent periodontal defects after third molar surgery? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MANDIBULAR 2ND MOLARS; SURGICAL REMOVAL; GTR TREATMENT; FLAP DESIGN; EXTRACTION; DISTAL AB Purpose: Among patients at high risk for second molar (M2) periodontal defects after third molar (M3) removal, does active treatment at the time of extraction, when compared with no treatment, alter the risk of postextraction M2 periodontal defects? Materials and Methods: We used a prospective cohort study design and a sample composed of subjects at high risk for developing M2 periodontal defects after M3 extraction, that is, age >= 26 years, pre-existing periodontal defects (attachment level [AL] >= 3 mm), and mesioangular or horizontal M3 impaction. The predictor variable was treatment status of the M3 extraction site. The M3 extraction sites were reconstructed with demineralized bone powder (DBP), bioresorbable guided tissue regeneration (GTR) therapy, or no treatment. The outcome variable was ALs measured at the M2 distobuccal line angle preoperatively and 26 weeks after extraction. Appropriate univariate, bivariate, and multivariate statistics were computed, and statistical significance was set at a value P <.05. Results: The cohort was composed of 12 subjects contributing 18 high-risk M3s. Twenty-six weeks after M3 removal, the ALs for GTR-treated (3.0 +/- 1.2 mm), DBP-treated (1.4 +/- 0.5 mm), and control (3.8 +/- 0.9) M3 sites were statistically significantly different (P =.002). Tukey post-hoc comparisons revealed a statistically significant difference between control and DBP ALs (P =.001) and GTR-treated and DBP-treated ALs (P.037). There was no statistically significant difference in ALs between control and GTR-treated M3s (P=.35). Conclusions: The results of this study suggest that subjects at high risk for developing M2 periodontal defects after M3 removal may benefit from the use of DBP placed at the time of M3 extraction to enhance periodontal healing. (C) 2005 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org FU NIDCR NIH HHS [K24-DE00448] NR 15 TC 11 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2005 VL 63 IS 7 BP 891 EP 896 DI 10.1016/j.joms.2005.03.003 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 941SD UT WOS:000230233600002 PM 16003612 ER PT J AU Ardekian, L Faquin, W Troulis, MJ Kaban, LB August, M AF Ardekian, L Faquin, W Troulis, MJ Kaban, LB August, M TI Synovial chondromatosis of the temporomandibular joint: Report and analysis of eleven cases SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OSTEOCHONDROMATOSIS; EXTENSION AB Purpose: Synovial chondromatosis (SC) is a benign monoarticular condition that is uncommon in the temporomandibular joint (TMJ). The purpose of this article is to present 11 additional cases of SC of the TMJ and discuss newer modes of imaging, diagnostic approaches, treatment options, and follow-up data. Methods: Medical records of 11 patients with SC treated within our department from 1991 to the present were reviewed. Demographic data, etiology, clinical presentation, diagnostic evaluation, treatment, and follow-up information were collected. Previously reported cases (both TMJ and others) from 1988 to present were identified for comparison and the literature reviewed. Results: There were 8 females and 3 males with an average age of 54 years. Pain and preauricular swelling were the most common presenting clinical complaints. Etiologic factors (parafunction, inflammatory joint disease) were found in 7 of 11 cases. Plain radiographs showed joint calcifications in only 2 of 11 cases. Computed tomography identified calcifications in 3 of 6. Magnetic resonance imaging clearly demonstrated the mass and its extension in 10 of 10 cases. Fine needle aspiration was diagnostic in 4 of 9. All patients were treated with an open arthrotomy. Meniscectomy was required in 7 of 11. Average follow-up was 5.2 years with no recurrences reported. Conclusion: The current case series of SC shows a female predilection with age and presenting complaints similar to those previously reported. A traumatic etiology was not identified, although a weak association is reported in the literature. The superiority of magnetic resonance imaging for both diagnosis and evaluation of extension of disease is shown. In a subset of cases, fine needle aspiration is useful for confirming the clinicoradiographic impression. Complete removal of involved tissue is associated with an excellent prognosis. (C) 2005 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Rambam Med Ctr, Haifa, Israel. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP August, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM maugust@partners.org FU PHS HHS [K23 1200 209103] NR 34 TC 34 Z9 38 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2005 VL 63 IS 7 BP 941 EP 947 DI 10.1016/j.joms.2005.03.009 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 941SD UT WOS:000230233600009 PM 16003619 ER PT J AU Bragdon, CR Martell, JM Estok, DM Greene, ME Malchau, H Harris, WH AF Bragdon, CR Martell, JM Estok, DM Greene, ME Malchau, H Harris, WH TI A new approach for the Martell 3-D method of measuring polyethylene wear without requiring the cross-table lateral films SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE total hip replacement; polyethylene; wear; radiograph ID TOTAL HIP-ARTHROPLASTY; RADIO STEREOMETRIC ANALYSIS; FEMORAL-HEAD; RADIOGRAPHIC EVALUATION; ACETABULAR CUPS; REPLACEMENT; PENETRATION; ACCURACY; LINER AB Due to the uneven and often inadequate quality of cross-table lateral hip radiographs, many radiographic studies of femoral head penetration into polyethylene in total hip arthroplasty are limited to the two-dimensional measurement of femoral head penetration using the A/P film only. We postulated that the use of two oblique frontal projections at 90 to each other would improve the three-dimensional evaluation. Using an established hip phantom, the idealized accuracy and precision of the three-dimensional Martell method was evaluated, contrasting the standard A/P and cross-table lateral projections versus a pair of oblique projections by four independent readers. Accuracy and precision resulting from the use of two oblique projections (average accuracy +/- 63 mu m, precision +/- 26 mu m) were similar to that obtained using the conventional A/P and cross-table lateral views (accuracy +/- 54 mu m, precision +/- 22 mu m), though the results of the two oblique views were slightly more variable. These observations suggest that by using two oblique A/P projections, the major disadvantage of using the cross-table lateral films, namely the variable quality of the images, is avoided. Perhaps, therefore, the utility and availability of three-dimensional data in comparable clinical studies may be improved. (c) 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Chicago, Dept Orthopaed, Chicago, IL 60637 USA. Univ Gothenburg, Inst Surg Sci, Dept Orthopaed, Gothenburg, Sweden. Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. EM cbragdon@partners.org NR 21 TC 13 Z9 13 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JUL PY 2005 VL 23 IS 4 BP 720 EP 725 DI 10.1016/j.orthres.2004.07.008 PG 6 WC Orthopedics SC Orthopedics GA 950LU UT WOS:000230859500005 PM 16022982 ER PT J AU Li, GA DeFrate, LE Rubash, HE Gill, TJ AF Li, GA DeFrate, LE Rubash, HE Gill, TJ TI In vivo kinematics of the ACL during weight-bearing knee flexion (vol 23, pg 340, 2005) SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Correction C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02115 USA. EM glil@partners.org NR 1 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUL PY 2005 VL 23 IS 4 BP 977 EP 977 DI 10.1016/j.orthres.2005.03.001 PG 1 WC Orthopedics SC Orthopedics GA 950LU UT WOS:000230859500039 ER PT J AU Qin, C Wang, JW Wei, Q She, MP Marasco, WA Jiang, H Tu, XM Zhu, H Ren, LL Gao, H Guo, L Huang, L Yang, RQ Cong, Z Guo, L Wang, YB Liu, YL Sun, YL Duan, SM Qu, JG Chen, LB Tong, W Ruan, L Liu, PM Zhang, H Zhang, JM Zhang, HY Liu, DP Liu, Q Hong, T He, W AF Qin, C Wang, JW Wei, Q She, MP Marasco, WA Jiang, H Tu, XM Zhu, H Ren, LL Gao, H Guo, L Huang, L Yang, RQ Cong, Z Guo, L Wang, YB Liu, YL Sun, YL Duan, SM Qu, JG Chen, LB Tong, W Ruan, L Liu, PM Zhang, H Zhang, JM Zhang, HY Liu, DP Liu, Q Hong, T He, W TI An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus SO JOURNAL OF PATHOLOGY LA English DT Article DE SARS; coronavirus; animal model; pathology; rhesus monkey ID ACUTE RESPIRATORY SYNDROME; LUNG PATHOLOGY; IDENTIFICATION; VIRUS; CHINA AB A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS. (c) Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Chinese Acad Med Sci, Inst Basic Med Sci, Dept Immunol, Beijing 100005, Peoples R China. PUMC, Beijing 100005, Peoples R China. Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China. PUMC, Beijing, Peoples R China. Chinese Ctr Dis Control & Prevent, Inst Virol, Beijing 100052, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP He, W (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Dept Immunol, 5 Dong Dan San Tiao, Beijing 100005, Peoples R China. EM heweiimu@public.bta.net.cn RI Zhang, Jianmin/C-8061-2011; Zhang, Huiyuan/J-2784-2016 FU NIAID NIH HHS [AI-061318] NR 24 TC 54 Z9 63 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JUL PY 2005 VL 206 IS 3 BP 251 EP 259 DI 10.1002/path.1769 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 941TI UT WOS:000230236700001 PM 15892035 ER PT J AU Stevens, R Rusch, D Solt, K Raines, DE Davies, PA AF Stevens, R Rusch, D Solt, K Raines, DE Davies, PA TI Modulation of human 5-hydroxytryptamine type 3AB receptors by volatile anesthetics and n-alcohols SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MINIMUM ALVEOLAR CONCENTRATION; GATED ION-CHANNEL; 5-HT3 RECEPTORS; NEUROBLASTOMA-CELLS; RAT; SUBUNIT; NEURONS; INTERNEURONS; GABA; EXCITATION AB Functional 5-hydroxytryptamine type 3 (5-HT3) receptors can be formed by 5-HT3A subunits alone or in combination with the 5-HT3B subunit, but only the 5-HT3A receptor has been previously studied with respect to the modulation by volatile anesthetics and n-alcohols. Using two-electrode voltage-clamp, we show for the first time the modulation of heteromeric human (h) 5-HT3AB receptors, expressed in Xenopus oocytes, by a series of n-alcohols and halogenated volatile anesthetics. At twice their anesthetic concentration, compounds having a molecular volume of less than 110 angstrom(3) enhanced submaximal 5-HT-evoked current. Compounds larger than 110 angstrom(3) inhibited submaximal 5-HT-evoked current. In experiments examining 5-HT concentration-response relationships, chloroform and butanol caused a slight decrease in the 5-HT EC50. Sevoflurane and octanol inhibited 5-HT-evoked current at all 5-HT concentrations tions tested but had no effect upon the 5-HT EC50. Compared with previous data on homomeric h5-HT3A receptors, the presence of the h5-HT3B subunit reduces the enhancement of h5-HT3 3 receptors by smaller halogenated volatile anesthetics and n-alcohols. In summary, these results suggest that heteromeric h5-HT3AB receptors are modulated by halogenated volatile anesthetics at clinically relevant concentrations, in addition to n-alcohols, suggesting that these receptors may be another physiological target for these compounds. The modulation is dependent upon the molecular volume of the compound, further supporting the concept of an anesthetic binding pocket of limited volume common on other Cys-loop ligand-gated ion channels. Incorporation of the 5-HT3B subunit alters either the anesthetic binding site or the allosteric interactions between anesthetic binding and channel opening. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, Boston, MA 02114 USA. Univ Hosp Marburg, Dept Anesthesia & Intens Care, Marburg, Germany. Univ Calif San Diego, Program Neurosci, San Diego, CA 92103 USA. RP Davies, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, 55 Fruit St, Boston, MA 02114 USA. EM pdavies2@partners.org OI Davies, Paul/0000-0002-3973-3143; Solt, Ken/0000-0001-5328-2062 FU NIGMS NIH HHS [R01 GM061927, GM61927] NR 39 TC 35 Z9 37 U1 0 U2 0 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 JUL PY 2005 VL 314 IS 1 BP 338 EP 345 DI 10.1124/jpet.105.085076 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936GF UT WOS:000229842800039 PM 15831437 ER PT J AU Anderson, KS LaBaer, J AF Anderson, KS LaBaer, J TI The sentinel within: Exploiting the immune system for cancer biomarkers SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE tumor antigen; antibody; protein array; proteomics; tumor immunology; biomarkers ID TUMOR-ASSOCIATED ANTIGENS; POSTTRANSLATIONAL PROTEIN MODIFICATIONS; MINOR HISTOCOMPATIBILITY ANTIGEN; STEM-CELL TRANSPLANTATION; PROSTATE-SPECIFIC ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; HUMAN COLON-CANCER; BREAST-CANCER; LUNG-CANCER; P53 PROTEIN AB The release of proteins from tumors triggers an immune response in cancer patients. These tumor antigens arise from several mechanisms including tumor-specific alterations in protein expression, mutation, folding, degradation, or intracellular localization. Responses to most tumor antigens are rarely observed in healthy individuals, making the response itself a biomarker that betrays the presence of underlying cancer. Antibody immune responses show promise as clinical biomarkers because antibodies have long half-lives in serum, are easy to measure, and are stable in blood samples. However, our understanding of the specificity and the impact of the immune response in early stages of cancer is limited. The immune response to cancer, whether endogenous or driven by vaccines, involves highly specific T lymphocytes (which target tumor-derived pepticles bound to self-MHC proteins) and B lymphocytes (which generate antibodies to tumor-derived proteins). T cell target antigens have been identified either by expression cloning from tumor cDNA libraries, or by prediction based on patterns of antigen expression ("reverse immunology"). B cell targets have been similarly identified using the antibodies in patient sera to screen cDNA libraries derived from tumor cell lines. This review focuses on the application of recent advances in proteomics for the identification of tumor antigens. These advances are opening the door for targeted vaccine development, and for using immune response signatures as biomarkers for cancer diagnosis and monitoring. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Proteom, Boston, MA 02115 USA. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA117374-01, K08 CA 88444-03, K08 CA088444, P50 CA 89393-05, P50 CA089393, R33 CA 099191-02, R33 CA099191, U01 CA117374, U01 CA117374-02] NR 121 TC 160 Z9 172 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL-AUG PY 2005 VL 4 IS 4 BP 1123 EP 1133 DI 10.1021/pr0500814 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200010 PM 16083262 ER PT J AU Gillette, MA Mani, DR Carr, SA AF Gillette, MA Mani, DR Carr, SA TI Place of pattern in proteomic biomarker discovery SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE biomarker discovery; proteomics; diagnostic; mass spectrometry; serum/plasma; pattern; machine learning; pattern recognition; feature selection; classification ID ELECTRON-CAPTURE DISSOCIATION; FLIGHT-MASS-SPECTROMETRY; ACUTE RESPIRATORY SYNDROME; HUMAN PLASMA PROTEOME; CELL LUNG-CANCER; SELDI-TOF-MS; LIQUID-CHROMATOGRAPHY; OVARIAN-CANCER; PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA AB The role of pattern in biomarker discovery and clinical diagnosis is examined in its historical context. The use of MS-derived pattern is treated as a logical extension of prior applications of non-MS-derived pattern. Criticisms pertaining to specific technology platforms and analytic methodologies are considered separately from the larger issues of pattern utility and deployment in biomarker discovery. We present a hybrid strategy that marries the desirable attributes of high-information content MS pattern with the capability to obtain identity, and explore the key steps in establishing a data analysis pipeline for pattern-based biomarker discovery. C1 MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Cambridge, MA 02141 USA. RP Gillette, MA (reprint author), MIT, Broad Inst, 320 Charles St, Cambridge, MA 02141 USA. EM gillette@broad.mit.edu; scarr@broad.mit.edu NR 92 TC 61 Z9 65 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL-AUG PY 2005 VL 4 IS 4 BP 1143 EP 1154 DI 10.1021/pr0500962 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200013 PM 16083265 ER PT J AU Lacerda, ALT Brambilla, P Sassi, RB Nicoletti, MA Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Lacerda, ALT Brambilla, P Sassi, RB Nicoletti, MA Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Anatomical MRI study of corpus callosum in unipolar depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE neuroimaging; Corpus callosuni; mood disorders; major depressive disorder; magnetic resonance imaging ID SUBGENUAL PREFRONTAL CORTEX; MAJOR DEPRESSION; MOOD DISORDERS; MAGNETIC-RESONANCE; BIPOLAR DISORDER; FIBER COMPOSITION; LOBE DYSFUNCTION; ABNORMALITIES; BRAIN; SCHIZOPHRENIA AB Previous studies have suggested abnormal cerebral lateralization in major depressive disorder (MDD). Few controlled MRI studies have investigated the corpus callosum (CC), the largest commissura connecting the two cerebral hemispheres, in MDD. This study investigated anatomical abnormalities in the CC and its subdivisions in MDD patients. Twenty-two unmedicated MDD patients and 39 healthy subjects underwent brain magnetic resonance imaging (MRI). Measurements of the CC and its sub-regions were performed with a semi-automated software (NIH Image, version 1.62). ANCOVA with age, gender, and intra-cranial volume (ICV) as covariates showed no significant differences in CC measurements between patients and controls (df = 1,56; p > 0.05). However, patients with familial MDD had a significantly larger middle germ area (F-1.45 = 4.252; p = 0.045) compared to healthy controls, and significantly larger middle genu (F-1.13 = 5.366; p = 0.037), anterior splenium (F-1.13 = 6.27; p = 0.026), and middle splenium areas (F-1.13 = 4.706; p = 0.049) compared to patients with non-familial MDD. Although preliminary, our findings suggest that anatomical abnormalities in CC may be restricted to patients with familial MDD, with possible enlargement of CC in this particular sub-group. The possible role of callosal abnormalities in the pathogenesis of mood disorders should be further examined. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Greater ABC UniABC, Dept Psychol, Santo Andre, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15261 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr,MC 7792, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI Lacerda, Acioly/A-7052-2010; brambilla, paolo/B-4184-2010 OI Lacerda, Acioly/0000-0002-9370-0449; brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH01736, MH30915] NR 53 TC 53 Z9 53 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUL PY 2005 VL 39 IS 4 BP 347 EP 354 DI 10.1016/j.jpsychires.2004.10.001 PG 8 WC Psychiatry SC Psychiatry GA 942QC UT WOS:000230295900002 PM 15804385 ER PT J AU Fausti, SA Wilmington, DJ Helt, PV Helt, WJ Konrad-Martin, D AF Fausti, SA Wilmington, DJ Helt, PV Helt, WJ Konrad-Martin, D TI Hearing health and care: The need for improved hearing loss prevention and hearing conservation practices SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE antioxidant; auditory brainstem response; early detection; hearing conservation; hearing protection; noise-induced hearing loss; otoacoustic emission; ototoxic-induced hearing loss; prevention; tinnitus ID PRODUCT OTOACOUSTIC EMISSIONS; CISPLATIN-INDUCED OTOTOXICITY; NUTRITION EXAMINATION SURVEY; DRUG-INDUCED OTOTOXICITY; 3RD NATIONAL-HEALTH; HIGH-FREQUENCY; DISTORTION-PRODUCT; ANTIOXIDANT SYSTEM; SODIUM THIOSULFATE; AUDITORY FUNCTION AB Hearing loss affects 31 million Americans, particularly veterans who were exposed to harmful levels of noise during military Functions. Many veterans also receive treatment with ototoxic medications, which may exacerbate preexisting hearing loss. Thus, hearing loss is the most common and tinnitus the third most common service-connected disability among veterans. Poor implementation of hearing protection programs and a lack of audiometric testing during medical treatment leave veterans vulnerable to unrecognized and untreated hearing loss until speech communication is impaired. Individualized audiometric testing techniques, including assessment of high frequencies, can be used in clinical and occupational settings to detect early hearing loss. Antioxidants also may alleviate cochlear damage Caused by noise and ototoxicity. Ultimately, hearing loss prevention requires education on reducing Occupational and recreational noise exposure and Counseling on the risks and options available to patients. Technological advances will improve monitoring, allow better noise engineering controls, and lead to more effective hearing protection. C1 Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Rehabil Res & Dev Serv, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Fausti, SA (reprint author), Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Rehabil Res & Dev Serv, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM stephen.fausti@med.va.gov RI Legarth, Jonas/A-9156-2012 NR 108 TC 40 Z9 47 U1 3 U2 17 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2005 VL 42 IS 4 SU 2 BP 45 EP 61 DI 10.1682/JRRD.2005.02.0039 PG 17 WC Rehabilitation SC Rehabilitation GA 019OE UT WOS:000235845800005 PM 16470464 ER PT J AU Lim, HK Sherwood, AM AF Lim, HK Sherwood, AM TI Reliability of surface electromyographic measurements from subjects with spinal cord injury during voluntary motor tasks SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE central nervous system; electromyography; lower limb; muscle (voluntary); quantitative evaluation; rehabilitation; reliability; similarity index; spinal cord injury; surface electromyography ID EMG VARIABLES; ISOMETRIC CONTRACTIONS; MUSCLE; GAIT; REPEATABILITY; STIMULATION; ACTIVATION; LOCOMOTION; PATTERNS; FATIGUE AB In this study, the reliability of surface electromyographic data (root-mean-square) for volitional motor tasks drawn from a standardized protocol was assessed. For each motor task, 5 s epochs of data were analyzed with a new method to generate a measure called the voluntary response index (VPI). The VRI consists of two components, magnitude and similarity index (SI), that were separately analyzed for repeatability. We examined three repetitions of each of 10 volitional motor tasks in 69 subjects with spinal cord injury (American Spinal Injury Association [ASIA] Impairment Scale [AIS], classifications C and D: 34 AIS-C and 35 AIS-D) for short-term (within-day) reliability. In 6 of the 69 subjects (3 each, AIS-C and AIS-D), the entire Study was repeated after I week and results were assessed for intermediateterm (I week apart) reliability. The reliability of the method for voluntary motor tasks was assessed by intraclass correlation coefficient (ICC), analysis of variance, coefficient of variance, and Pearson's correlation. Good reliability was found for magnitude (ICC = 0.71-0.99, Pearson's r = 0.77-0.99) and for SI (ICC = 0.65-0.96, Pearson's r = 0.72-0.93) for three repeated tests (within-day). Significant difference was found for studies completed I week apart for magnitude (p = 0.02) but not for SI (p = 0.57). In addition, SI showed less variation than magnitude (p < 0.001). No significant difference of magnitude and SI between tasks was observed. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Lim, HK (reprint author), Korea Res Inst Stand & Sci, Biomagnetism Res Ctr, Div Electromagnet Metrol, 1 Doryong Dong, Taejon 305340, South Korea. EM hlim@kriss.re.kr OI Sherwood, Arthur/0000-0002-0110-4317 NR 38 TC 14 Z9 14 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2005 VL 42 IS 4 BP 413 EP 421 DI 10.1682/JRRD.2004.07.0079 PG 9 WC Rehabilitation SC Rehabilitation GA 995NB UT WOS:000234105900006 PM 16320138 ER PT J AU Koontz, AM Cooper, RA Boninger, ML Yang, YS Impink, BG van der Woude, LHV AF Koontz, AM Cooper, RA Boninger, ML Yang, YS Impink, BG van der Woude, LHV TI A kinetic analysis of manual wheelchair propulsion during start-up on select indoor and outdoor surfaces SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Biomechanics CY SEP 25-27, 2003 CL Toledo, OH SP Amer Soc Biomech DE access; biomechanics; community access; driving surfaces; manual wheelchair; propulsion forces; ramps; rolling resistance; sidewalks; standards; surface resistances; wheelchair propulsion ID SPINAL-CORD INJURIES; MECHANICAL EFFICIENCY; UPPER EXTREMITY; NERVE FUNCTION; ENERGY-COST; USERS; BIOMECHANICS; WEIGHT; PEOPLE AB The objective of this study was to conduct a kinetic analysis of manual wheelchair propulsion during start-LIP on select indoor and Outdoor surfaces. Eleven manual wheelchairs were fitted with a SMART(Wheel) and their users were asked to Push on a Course consisting of high- and low-pile carpet, indoor tile, interlocking concrete pavers, smooth level concrete, grass, hardwood flooring, and a sidewalk with a 5-degree grade. Peak resultant force, wheel torque, mechanical effective force, and maximum resultant force rate of rise were analyzed during start-up for each Surface and normalized relative to their steady-state values on the smooth level concrete. Additional variables included peak velocity, distance traveled, and number of strokes in the first 5 s of the trial. We compared biomechanical data between surfaces using repeated-measures mixed models and paired comparisons with a Bonferroni adjustment. Applied resultant force (p = 0.0154), wheel torque (p < 0.0001), and mechanical effective force (p = 0.0047) were significantly different between surfaces. The kinetic values for grass, interlocking pavers, and ramp ascent were typically higher compared with tile, wood, smooth level concrete, and high- and low-pile carpet. Users were found to travel shorter distances up the ramp and across grass (p < 0.0025) and had a higher stroke Count on the ramp (p = 0.0124). While peak velocity was not statistically different, average velocity was slower for the ramp and grass, which indicates greater wheelchair/user deceleration between strokes. The differences noted between surfaces highlight the importance of evaluating wheelchair propulsion ability over a range of surfaces. C1 Dept Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Hlth Syst, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Vrije Univ, Fac Human Movement Sci, Inst Fundamental & Clin Human Movement Sci, Amsterdam, Netherlands. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R 1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Yang, Yu-Sheng/0000-0002-2767-9354; Boninger, Michael/0000-0001-6966-919X NR 32 TC 47 Z9 47 U1 4 U2 13 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2005 VL 42 IS 4 BP 447 EP 458 DI 10.1682/JRRD.2004.08.0106 PG 12 WC Rehabilitation SC Rehabilitation GA 995NB UT WOS:000234105900009 PM 16320141 ER PT J AU Sevick, MA Piraino, B Sereika, S Starrett, T Bender, C Bernardini, J Stark, S Burke, LE AF Sevick, MA Piraino, B Sereika, S Starrett, T Bender, C Bernardini, J Stark, S Burke, LE TI A preliminary study of PDA-based dietary self-monitoring in hemodialysis patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID C-REACTIVE PROTEIN AB Objective: The purpose of this study was to pilot test an intervention to enhance the adherence of study participants to the hemodialysis dietary regimen. Design: A single case study design was used to examine the potential effectiveness of the intervention over a 4-month period of time. Setting: A dialysis center in southwestern Pennsylvania. Patients: Of the five individuals entered into the study, one was male and four were female, four were black, and one was white. Participants were 63 to 70 years of age, and had been receiving dialysis for a median of 36 months (range, 18 to 84 months). Intervention: The intervention included counseling to enhance self-efficacy, by a renal dietitian, paired with personal digital assistant-based dietary self-monitoring. Participants met twice per week with interventionists during the first 6 weeks, weekly during the second 6-week period, and biweekly in the final 4-week period. Main outcome measures: Monthly laboratory data regarding serum albumin, potassium, and phosphorus levels; Kt/V; and data on average monthly interdialytic weight gain were abstracted from the participants' medical records. C-reactive protein level was determined at baseline and at 4 months. Results: Four of five study participants had an increase in serum albumin level from baseline to their final measurement, and one participant maintained a stable albumin level. Four of five participants also experienced a small increase in serum phosphorus level. Mixed results were obtained with regard to serum potassium and average monthly interdialytic weight gain. Conclusions: Because of the small sample and single case study design, caution must be used in drawing firm conclusions from this study. Data suggest that the intervention may result in improved dietary intake and improved serum albumin levels. With increased dietary intake, serum phosphorus levels may increase. Additional research is needed to determine the potential efficacy and cost-effectiveness of this intervention for improving dietary adherence. (c) 2005 by the National Kidney Foundation, Inc. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Sevick, MA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C, Pittsburgh, PA 15240 USA. EM mary.sevick@med.pd.gov OI Piraino, Beth/0000-0001-5061-0841 FU NCRR NIH HHS [5M01-RR00056]; NIDDK NIH HHS [DK-046204]; NINR NIH HHS [P30-NR03924] NR 19 TC 20 Z9 20 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2005 VL 15 IS 3 BP 304 EP 311 DI 10.1016/j.jrn.2005.04.003 PG 8 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 949GN UT WOS:000230773200004 PM 16007560 ER PT J AU Weisbart, RH Min, Y Wong, AL Kang, J Kwunyeun, S Lin, A Kim, J Chan, G Wakelin, R Sohn, W Chang, SS Nishimura, RN AF Weisbart, RH Min, Y Wong, AL Kang, J Kwunyeun, S Lin, A Kim, J Chan, G Wakelin, R Sohn, W Chang, SS Nishimura, RN TI Selective IgA immune unresponsiveness to Proteus mirabilis fumarate reductase A-chain in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE Proteus mirabilis; rheumatoid arthritis; antibodies; immune tolerance; antibody response ID ANTIPROTEUS ANTIBODIES; RADIOLOGICAL PROGRESSION; HELICOBACTER-PYLORI; FECAL FLORA; DISEASE; ANTIGEN AB Objective. To determine if selective immune unresponsiveness to microbial antigens is associated with predisposition to rheumatoid arthritis (RA). Methods. Proteins from Proteus mirabilis lysate were isolated by SDS-PAGE and examined by Western blotting for antibody responses in sera from patients with RA compared to healthy subjects and patients with psoriatic arthritis (PsA). Results. Although RA patients had marked IgA immune responses to many P. mirabilis proteins compared to healthy subjects, selective unresponsiveness was found in RA to a 66 kDa protein identified as fumarate reductase A-chain (FRD-A) by mass spectroscopy. This was confirmed in Western blots with recombinant FRD-A from P. mirabilis. IgA unresponsiveness to FRD-A was found in 21/59 (35.6%) RA patients compared to 7/63 (11.1%) healthy individuals (p < 0.01) and 6/52 (11.5%) patients with PsA (p < 0.01). IgA unresponsiveness to FRD-A was present in 20/46 (43.5%) RA patients with IgA rheumatoid factors (RF) compared to 1/13 (7.7%) without RF (p < 0.025). Conclusion. Our results identify a selective bole in the IgA immune repertoire for P. mirabilis FRDA in a subset of IgA RF-positive patients with RA. C1 VAGLAHS 11S, Dept Med, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Med Ctr, Dept Med, Sylmar, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Weisbart, RH (reprint author), VAGLAHS 11S, Dept Med, 16111 Plummer St, Sepulveda, CA 91343 USA. EM tweisbar@ucla.edu NR 34 TC 5 Z9 5 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2005 VL 32 IS 7 BP 1208 EP 1212 PG 5 WC Rheumatology SC Rheumatology GA 945WA UT WOS:000230532000008 PM 15996053 ER PT J AU Gastfriend, DR Donovan, D Lefebvre, R Murray, KT AF Gastfriend, DR Donovan, D Lefebvre, R Murray, KT TI Developing a baseline assessment battery: Balancing patient time burden with essential clinical and research monitoring SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID COMPULSIVE DRINKING SCALE; ALCOHOL-USE DISORDERS; QUALITY-OF-LIFE; ADDICTIVE BEHAVIORS; PROBLEM DRINKERS; CONTROLLED-TRIAL; SELF-EFFICACY; DOUBLE-BLIND; NALTREXONE; DEPENDENCE AB Objective: Baseline assessment in a multisite alcohol-dependence treatment study has several purposes: addressing inclusion/exclusion criteria and characterizing participants to illuminate subsequent efficacy and safety patterns of the interventions. Combination pharmacotherapy and behavioral therapy trials, however, require more complex assessments than single-modality studies. Medication trials require measures of initial safety for study drug as well as for subsequent side-effect and adverse-effect monitoring (e.g., physical examination, laboratory markers, somatic symptoms, medical conditions and concomitant medications). Behavioral therapy trials (and in some cases medication trials) warrant baseline measurement of mediators of therapy effect (e.g., prior treatment history, motivation for change, self-efficacy, other psychiatric conditions, treatment expectations and network supports). Measures may be needed to interpret interactions that may be discovered between these modalities. Method: The National Institute on Alcohol Abuse and Alcoholism COMBINE Study evaluated the potentially overwhelming number of candidate instruments through an iterative process, using the following sequence to finalize a rational baseline assessment battery: key constructs, representative measures, determination of duration of assessment, risk of assessment reactivity, goal priorities, necessity for measure "pruning" and order of measure presentation. After selecting the draft battery, feasibility was evaluated in a pilot study prior to the main trial. Results: The battery was feasible to administer and avoided unintended selection bias. Dropout was substantial, however, and differences across sites in baseline assessment completion rates reflected a tendency of a central intake model to function as an initial filter of dropouts, compared with a direct recruitment model. Conclusions: This process holds several potentially useful lessons for investigators. C1 Massachusetts Gen Hosp, Addict Res Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gastfriend, DR (reprint author), Alkermes Inc, 88 Sidney St, Cambridge, MA 02139 USA. EM david.gastfriend@alkermes.com FU NIAAA NIH HHS [U10AA11716, U10AA11773, U10AA11776, U10AA11715, U10AA11799, U10AA11787, U10AA11727, U10AA11756, U10AA11768, U10AA11777, U10AA11783] NR 80 TC 1 Z9 1 U1 5 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 2005 SU 15 BP 94 EP 103 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 958KS UT WOS:000231445600016 PM 16223061 ER PT J AU Shera, CA Tubis, A Talmadge, CL AF Shera, CA Tubis, A Talmadge, CL TI Coherent reflection in a two-dimensional cochlea: Short-wave versus long-wave scattering in the generation of reflection-source otoacoustic emissions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MIDDLE-EAR TRANSMISSION; BASILAR-MEMBRANE; 3-DIMENSIONAL MODEL; LIOUVILLE-GREEN; FINE-STRUCTURE; STIMULUS; DIFFERENCE; MECHANICS; APPROXIMATION; PROPAGATION AB The theory of coherent reflection filtering explains the empirical form of the cochlear reflectance by showing how it emerges from the coherent "backscattering" of forward-traveling waves by impedance perturbations in the mechanics of the cochlear partition. Since the theory was developed using the one-dimensional (I-D) transmission-line model of the cochlea, an obvious logical shortcoming is the failure of the long-wavelength approximation near the peak of the traveling wave, where coherent backscattering is purported to occur. Indeed, existing theory suggests that wave reflection may be strongly suppressed in the short-wave regime. To understand how short-wave behavior near the peak modifies the predictions of the long-wave theory, this paper solves the scattering problem in the 2-D cochlear model. The 2-D problem is reduced to a I -D wave equation and the solution expressed as an infinite series in which successive terms arise via multiple scattering within the cochlea. The cochlear reflectance is computed in response-matched models constructed by solving the inverse problem to control for variations in mechanical tuning among models of different heights and dimensionality. Reflection from the peak region is significantly enhanced by the short-wave hydrodynamics, but other conclusions of the I-D analysis-such as the predicted relation between emission group delay and the wavelength of the traveling wave-carry, over with only minor modifications. The results illustrate the important role of passive hydromechanical effects in shaping otoacoustic emissions and cochlear tuning. (c) 2005 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA. Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC003094, R01 DC003687] NR 93 TC 51 Z9 53 U1 0 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2005 VL 118 IS 1 BP 287 EP 313 DI 10.1121/1.1895025 PG 27 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 943LU UT WOS:000230356200025 PM 16119350 ER PT J AU Sequist, TD Gandhi, TK Karson, AS Fiskio, JM Bugbee, D Sperling, M Cook, EF Orav, EJ Fairchild, DG Bates, DW AF Sequist, TD Gandhi, TK Karson, AS Fiskio, JM Bugbee, D Sperling, M Cook, EF Orav, EJ Fairchild, DG Bates, DW TI A randomized trial of electronic clinical reminders to improve quality of care for diabetes and coronary artery disease SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med ID PRACTICE GUIDELINES COMMITTEE; DECISION-SUPPORT-SYSTEMS; ASSOCIATION TASK-FORCE; COMPUTERIZED REMINDERS; AMERICAN-COLLEGE; PREVENTIVE CARE; MANAGEMENT; ADULTS; IMPLEMENTATION; METAANALYSIS AB Objective: The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease (CAD) care and to assess physician attitudes toward this reminder system. Design: We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics. Clinics were randomized so that physicians received either evidence-based electronic reminders within their patients' electronic medical record or usual care. There were five reminders for diabetes care and four reminders for CAD care. Measurements: The primary outcome was receipt of recommended care for diabetes and CAD. We created a summary outcome to assess the odds of increased compliance with overall diabetes care (based on five measures) and overall CAD care (based on four measures). We surveyed physicians to assess attitudes toward the reminder system. Results: Baseline adherence rates to all quality measures were low. While electronic reminders increased the odds of recommended diabetes care (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.67) and CAD (OR 1.25, 95% CI 1.01-1.55), the impact of individual reminders was variable. A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD. The majority of physicians (76%) thought that reminders improved quality of care. Conclusion: An integrated electronic reminder system resulted in variable improvement in care for diabetes and CAD. These improvements were often limited and quality gaps persist. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02120 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Partners HealthCare Syst, Boston, MA USA. RP Bates, DW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St, Boston, MA 02120 USA. EM dbates@partners.org FU AHRQ HHS [5 U18 HS011046] NR 32 TC 141 Z9 142 U1 11 U2 17 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2005 VL 12 IS 4 BP 431 EP 437 DI 10.1197/jamia.M1788 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 950LR UT WOS:000230859200009 PM 15802479 ER PT J AU Saleem, JJ Patterson, ES Militello, L Render, ML Orshansky, G Asch, SM AF Saleem, JJ Patterson, ES Militello, L Render, ML Orshansky, G Asch, SM TI Exploring barriers and facilitators to the use of computerized clinical reminders SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID DECISION-SUPPORT-SYSTEMS; CARE; QUALITY AB Objective: Evidence-based practices in preventive care and chronic disease management are inconsistently implemented. Computerized clinical reminders (CRs) can improve compliance with these practices in outpatient settings. However, since clinician adherence to CR recommendations is quite variable and declines over time, we conducted observations to determine barriers and facilitators to the effective use of CRs. Design: We conducted an observational study of nurses and providers interacting with CRs in outpatient primary care clinics for two days in each of four geographically distributed Veterans Administration (VA) medical centers. Measurements: Three observers recorded interactions of 35 nurses and 55 physicians and mid-level practitioners with the CRs, which function as part of an electronic medical record. Field notes were typed, coded in a spreadsheet, and then sorted into logical categories. We then integrated findings across observations into meaningful patterns and abstracted the data into themes, such as recurrent strategies. Several of these themes translated directly to barriers and facilitators to effective CR use. Results: Optimally using the CR system for its intended purpose was impeded by (1) lack of coordination between nurses and providers; (2) using the reminders while not with the patient, impairing data acquisition and/or implementation of recommended actions; (3) workload; (4) lack of CR flexibility; and (5) poor interface usability. Facilitators included (1) limiting the number of reminders at a site; (2) strategic location of the computer workstations; (3) integration of reminders into workflow; and (4) the ability to document system problems and receive prompt administrator feedback. Conclusion: We identified barriers that might explain some of the variability in the use of CRs. Although these barriers may be difficult to overcome, some strategies may increase user acceptance and therefore the effectiveness of the CRs. These include explicitly assigning responsibility for each CR to nurses or providers, improving visibility of positive results from CRs in the electronic medical record, creating a feedback mechanism about CR use, and limiting the overall number of CRs. C1 VAMC, VA GAPS Ctr, Cincinnati, OH 45220 USA. Ohio State Univ, Inst Ergon, Columbus, OH 43210 USA. Univ Dayton, Res Inst, Dayton, OH 45469 USA. Univ Cincinnati, Coll Med, Dept Internal Med, Div Pulm Crit Care, Cincinnati, OH USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Saleem, JJ (reprint author), VAMC, VA GAPS Ctr, 3200 Vine St,MDP 111, Cincinnati, OH 45220 USA. EM Jason.Saleem@med.va.gov RI Patterson, Emily/B-4398-2011; OI Patterson, Emily/0000-0002-4514-2075; Militello, Laura G/0000-0001-8445-5640 NR 21 TC 106 Z9 107 U1 3 U2 20 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2005 VL 12 IS 4 BP 438 EP 447 DI 10.1197/jamia.M1777 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 950LR UT WOS:000230859200010 PM 15802482 ER PT J AU Haas, CE Lin, L Cloen, D Kufel, T Moon, R Frerichs, V AF Haas, Curtis E. Lin, Lydia Cloen, Denise Kufel, Thomas Moon, Richard Frerichs, Valerie TI Omeprazole absorption from a compounded Transdermal formulation in healthy volunteers SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE transdermal drug administration; omeprazole; pharmacokinetics; compounding ID STRUCTURE-PERMEABILITY RELATIONSHIPS; SKIN PERMEABILITY; DELIVERY; DRUGS AB Objective: To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. Design: Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. Setting: Academic clinical research center. Participants: Eight healthy volunteers between 18 and 50 years of age. Interventions: Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. Main Outcome Measures: PK parameters ( maximal plasma concentration [C(max)], the time of C(max) [T(max)], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. Results: Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (+/- SD) C(max) was 0.153 +/- 0.241 ng/mL, and the T(max) in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000- fold lower than those observed with oral dosing. Conclusion: Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule. C1 [Haas, Curtis E.] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharm Practice, Buffalo, NY 14260 USA. [Haas, Curtis E.; Cloen, Denise] Clin Res Ctr, US Dept Vet Affairs, Buffalo, NY USA. [Kufel, Thomas] Dept Med, Buffalo, NY USA. [Moon, Richard] Pharm Innovat, Jamestown, NY USA. RP Haas, CE (reprint author), SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharm Practice, 311 Hochstetter Hall, Buffalo, NY 14260 USA. EM haas@buffalo.edu FU NCRR NIH HHS [S10RR14572] NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JUL-AUG PY 2005 VL 45 IS 4 BP 473 EP 478 DI 10.1331/1544345054475603 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V47JM UT WOS:000203201800012 PM 16128503 ER PT J AU Wang, JC Riley, BM AF Wang, JC Riley, BM TI A new fixation technique for the lapidus bunionectomy SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID HALLUX-VALGUS AB Presented here is a preliminary report of 102 patients who underwent first metatarsocuneiform joint arthrodeses performed with external fixation for the correction of hallux valgus. The advantages of using external fixation are the ability to initiate early weightbearing, predictable fusion, and removal of all of the hardware postoperatively. In the 102 patients reported here, the average time to initiation of unassisted full weightbearing was 13.1 days. The average time to fusion was 5.3 weeks, with removal of the external fixator at an average of 5.5 weeks postoperatively. There was no incidence of delayed union or nonunion. There was one case of pin-tract irritation, which resolved with appropriate pin care and a short course of oral antibiotics. External fixation is an effective alternative to traditional internal fixation techniques in metatarsocuneiform joint arthrodesis. C1 Century City Hosp, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Wang, JC (reprint author), 2428 Santa Monica Blvd,Ste 100, Santa Monica, CA 90404 USA. NR 16 TC 14 Z9 15 U1 0 U2 2 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JUL-AUG PY 2005 VL 95 IS 4 BP 405 EP 409 PG 5 WC Orthopedics SC Orthopedics GA 947RI UT WOS:000230663500014 PM 16037560 ER PT J AU Davis, CL Delmonico, FL AF Davis, CL Delmonico, FL TI Living-donor kidney transplantation: A review of the current practices for the live donor SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POSITIVE CROSS-MATCH; STAGE RENAL-DISEASE; BODY-MASS INDEX; BLOOD-PRESSURE; FOLLOW-UP; UNITED-STATES; LAPAROSCOPIC NEPHRECTOMY; UNILATERAL NEPHRECTOMY; VENOUS THROMBOEMBOLISM; HEART-DISEASE AB The first successful living-donor kidney transplant was performed 50 yr ago. Since then, in a relatively brief period of medical history, living kidney transplantation has become the preferred treatment for those with ESRD. Organ replacement from either a live or a deceased donor is preferable to dialysis therapy because transplantation provides a better quality of life and improved survival. The advantages of live versus deceased donor transplantation now are readily apparent as it affords earlier transplantation and the best long-term survival. Live kidney donation has also been fostered by the technical advance of laparoscopic nephrectomy and immunologic maneuvers that can overcome biologic obstacles such as HLA disparity and ABO or cross-match incompatibility. Congressional legislation has provided an important model to remove financial disincentives to being a live donor. Federal employees now are afforded paid leave and coverage for travel expenses. Candidates for renal transplantation are aware of these developments, and they have become less hesitant to ask family members, spouses, or friends to become live kidney donors. Living donation as practiced for the past 50 yr has been safe with minimal immediate and long-term risk for the donor. However, the future experience may not be the same as our society is becoming increasingly obese and developing associated health problems. In this environment, predicting medical futures is less precise than in the past. Even so, isolated abnormalities such as obesity and in some instances hypertension are no longer considered absolute contraindications to donation. These and other medical risks bring additional responsibility in such circumstances to track the unknown consequences of a live-donor nephrectomy. C1 Univ Washington, Sch Med, Dept Med, Div Nephrol,Transplantat Serv, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Davis, CL (reprint author), Univ Washington, Sch Med, Dept Med, Div Nephrol,Transplantat Serv, Box 356174,1959 NE Pacific St, Seattle, WA 98195 USA. EM cdavis@u.washington.edu NR 80 TC 166 Z9 182 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2005 VL 16 IS 7 BP 2098 EP 2110 DI 10.1681/ASN.2004100824 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 939BK UT WOS:000230046900029 PM 15930096 ER PT J AU Kurella, M Chertow, GM Fried, LF Cummings, SR Harris, T Simonsick, E Satterfield, S Ayonayon, H Yaffe, K AF Kurella, M Chertow, GM Fried, LF Cummings, SR Harris, T Simonsick, E Satterfield, S Ayonayon, H Yaffe, K TI Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CARDIOVASCULAR HEALTH; RISK-FACTORS; HEMODIALYSIS-PATIENTS; RENAL-INSUFFICIENCY; PLASMA HOMOCYSTEINE; ALZHEIMERS-DISEASE; SERUM CREATININE; OLDER-ADULTS; DEMENTIA; STROKE AB Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment, Whether he longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score < 80 or a decline in 3MS > 5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores >= 80. Participants with CKD, defined as an estimated GFR (eGFR) < 60 ml/min per 1.73 m(2), were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [Cl] 1.03 to 1.69) and OR 2.43 (95% Cl, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m(2) and < 45 ml/min per 1.73 m(2), respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted. C1 Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Med, Div Neurol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Med, Div Psychiat, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Nephrol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Neurol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Psychiat, San Francisco, CA 94118 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. San Francisco Coordinating Ctr, San Francisco, CA USA. NIA, Intramural Res Program, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. RP Kurella, M (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, Laurel Hts,3333 Calif St,Suite 430, San Francisco, CA 94118 USA. EM kurella@itsa.ucsf.eclu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NIA NIH HHS [N01-AG-6-2106, AG00888, N01-AG-6-2101, N01-AG-6-2103]; NIDDK NIH HHS [R01 DK01005, R01 DK58411] NR 31 TC 191 Z9 198 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2005 VL 16 IS 7 BP 2127 EP 2133 DI 10.1681/ASN.2005010005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 939BK UT WOS:000230046900032 PM 15888561 ER PT J AU Gutierrez, O Isakova, T Rhee, E Shah, A Holmes, J Collerone, G Juppner, H Wolf, M AF Gutierrez, O Isakova, T Rhee, E Shah, A Holmes, J Collerone, G Juppner, H Wolf, M TI Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MODERATE RENAL-INSUFFICIENCY; VITAMIN-D METABOLISM; SECONDARY HYPERPARATHYROIDISM; PHOSPHATE HOMEOSTASIS; PARATHYROID-HORMONE; HYPOPHOSPHATEMIC RICKETS; FGF-23; HEMODIALYSIS; FGF23; MICE AB Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal la-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D-3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe,,,) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was < 30. Increased Fe,,, was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe-PO4. Increased FGF-23 and decreased 25(OH)D-3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe-PO4, and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Internal Med Residency Training Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pediat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Renal Unit, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Internal Med Residency Training Program, Bartlett 911,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org FU NCRR NIH HHS [K23RR017376, M01RR01066] NR 43 TC 444 Z9 476 U1 3 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2005 VL 16 IS 7 BP 2205 EP 2215 DI 10.1681/ASN.2005010052 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 939BK UT WOS:000230046900042 PM 15917335 ER PT J AU Pollard, JD Ropper, A Cros, D Vallat, JM Toal, M Dawson, K Riester, K AF Pollard, JD Ropper, A Cros, D Vallat, JM Toal, M Dawson, K Riester, K TI A randomized, double-blind, placebo-controlled, dose-ranging study of interferon beta-1a (Avonex (R)) in chronic inflammatory demyelinating polyradiculoneurbopathy SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Peripheral Nerve Society CY JUL, 2005 CL Tuscany, ITALY SP Peripheral Nerve Soc C1 Univ Sydney, Sydney, NSW 2006, Australia. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duputryen Univ Hosp, Limoges, France. Biogen Idec, Maidenhead, Berks, England. Biogen Idec, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUL PY 2005 VL 10 SU 1 BP 74 EP 74 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 942YY UT WOS:000230320000202 ER PT J AU Koo, L Kapadia, MK Singh, RP Sheridan, R Hatton, MP AF Koo, L Kapadia, MK Singh, RP Sheridan, R Hatton, MP TI Gender differences in etiology and outcome of open globe injuries SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID PENETRATING OCULAR INJURIES; EYE INJURIES; PROGNOSTIC FACTORS; TRAUMA; EPIDEMIOLOGY; CHILDREN; WOMEN; MEN AB Purpose: Patterns of injury and outcomes after multi-system trauma differ between men and women. Few data exist regarding the epidemiology of gender differences in severe eye trauma. We hypothesized that the incidence and patterns of open globe injuries might differ between men and women. Methods. charts of 220 patients with open globe injuries presenting to the Massachusetts Eye and Ear Infirmary during a three-year period were retrospectively reviewed. The data were analyzed with respect to gender, type of open globe injury (penetrating, perforating, or rupture), and mechanism of globe injury (projectile, non-projectile, assault, fall, sports, motor vehicle crash). Results. The majority (78.6%) of patients were men. Women with open globe injuries were older (median age 73 years) than men (median age 36 years). Men were more likely to suffer from penetrating injuries (69.9%) while women were more likely to experience blunt globe rupture (68.1%). Projectile objects accounted for the majority of open globe injuries in men (54.9%) and were an infrequent cause in women (4.3%). Nearly one-third (31.8%) of the projectile injuries in men were work-related, and 19.7% occurred during home improvement projects. Compared with men, falls were more frequently responsible for globe injuries in women (55.3 % versus 8.1 %). Injuries limited to the cornea were more common in men than women (46.2% versus 23.4%), while more posterior globe injuries were more common among women (46.8% versus 28.3 % men). Women were more likely than men to have poor visual acuity at 3 months after injury. Conclusions. The causes and patterns of open globe injuries differ between men and women. In this series, the majority of injuries to men were caused by projectile objects related to work or home improvement projects. Open globe injuries in women were most often resulted from fall, and were more likely to cause rupture posterior to the limbus. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hatton, MP (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Mark_Hatton@meei.harvard.edu NR 35 TC 24 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUL PY 2005 VL 59 IS 1 BP 175 EP 178 DI 10.1097/01.TA.0000173624.7438.D6 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 956ZN UT WOS:000231339000038 PM 16096559 ER PT J AU McDougal, WS Gervais, DA McGovern, FJ Mueller, PR AF McDougal, WS Gervais, DA McGovern, FJ Mueller, PR TI Long-term followup of patients with renal cell carcinoma treated with radio frequency ablation with curative intent SO JOURNAL OF UROLOGY LA English DT Article DE carcinoma; renal cell; kidney neoplasms AB Purpose: We defined the role of radio frequency ablation in the treatment of renal cell carcinoma. Materials and Methods: A total of 16 patients with biopsy proven renal cell carcinoma were treated with radio frequency ablation in an outpatient setting and followed for a minimum of 4 years. Results: Of the 16 patients 5 died before 4 years of followup of unrelated causes. All except 1 tumor was successfully treated. All patients with exophytic tumors were successfully treated. Conclusions: Radio frequency ablation of exophytic renal cell carcinomas less than 5 cm in diameter is effective in eradicating the tumor and comparable to surgical extirpation at 4 years. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 5 TC 117 Z9 122 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2005 VL 174 IS 1 BP 61 EP 63 DI 10.1097/01.ju.0000162046.45024.2b PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 937SS UT WOS:000229946400016 PM 15947578 ER PT J AU Dahl, DM AF Dahl, DM TI Classification and trends of perioperative morbidities following laparoscopic radical prostatectomy - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Dahl, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2005 VL 174 IS 1 BP 139 EP 139 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 937SS UT WOS:000229946400037 ER PT J AU Campbell, JA Schelling, P Wetzel, JD Johnson, EM Forrest, JC Wilson, GAR Aurrand-Lions, M Imhof, BA Stehle, T Dermody, TS AF Campbell, JA Schelling, P Wetzel, JD Johnson, EM Forrest, JC Wilson, GAR Aurrand-Lions, M Imhof, BA Stehle, T Dermody, TS TI Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus SO JOURNAL OF VIROLOGY LA English DT Article ID ATTACHMENT PROTEIN SIGMA-1; CENTRAL-NERVOUS-SYSTEM; CELLULAR RECEPTOR; SIALIC-ACID; MEASLES-VIRUS; ALPHA-DYSTROGLYCAN; CRYSTAL-STRUCTURE; TYPE-3 REOVIRUS; B VIRUSES; ADENOVIRUS AB Reovirus infectious are initiated by the binding of viral attachment protein sigma 1 to receptors on the surface of host cells. The sigma 1 protein is an elongated fiber comprised of an N-terminal tail that inserts into the virion and a C-terminal head that extends from the virion surface. The prototype reovirus strains type 1 Lang/53 (T1L/53) and type 3 Dearing/55 (T3D/55) use junctional adhesion molecule A (JAM-A) as a receptor. The C-terminal half of the T3D/55 sigma 1 protein interacts directly with JAM-A, but the determinants of receptor-binding specificity have not been identified. In this study, we investigated whether JAM-A also mediates the attachment of the prototype reovirus strain type 2 Jones/55 (T2J/55) and a panel of field-isolate strains representing each of the three serotypes. Antibodies specific for JAM-A were capable of inhibiting infections of HeLa cells by T1L/53, T2J/55, and T3D/55, demonstrating that strains of all three serotypes use JAM-A as a receptor. To corroborate these findings, we introduced JAM-A or the structurally related JAM family members JAM-B and JAM-C into Chinese hamster ovary cells, which are poorly permissive for reovirus infection. Both prototype and field-isolate reovirus strains were capable of infecting cells transfected with JAM-A but not those transfected with JAM-B or JAM-C. A sequence analysis of the sigma 1-encoding SI gene segment of the strains chosen for study revealed little conservation in the deduced sigma 1 amino acid sequences among the three serotypes. This contrasts markedly with the observed sequence variability within each serotype, which is confined to a small number of amino acids. Mapping of these residues onto the crystal structure of sigma 1 identified regions of conservation and variability, suggesting a likely mode of JAM-A binding via a conserved surface at the base of the sigma 1 head domain. C1 Vanderbilt Univ, Sch Med, Lamb Ctr Pediat Res, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Ctr Med Univ Geneva, Dept Pathol, Geneva, Switzerland. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Ctr Med Univ Geneva, Dept Pathol, Geneva, Switzerland. RP Dermody, TS (reprint author), Vanderbilt Univ, Sch Med, Lamb Ctr Pediat Res, D7235 MCN, Nashville, TN 37232 USA. EM terry.dermody@vanderbilt.edu RI Aurrand-Lions, Michel/O-9953-2016 OI Aurrand-Lions, Michel/0000-0002-8361-3034 FU NCI NIH HHS [T32 CA009385, T32 CA09385, P30 CA068485, CA68485]; NIAID NIH HHS [R01 AI38296, R01 AI038296]; NIDDK NIH HHS [P30 DK020593, DK20593, P60 DK020593]; NIGMS NIH HHS [R01 GM67853, R01 GM067853] NR 72 TC 58 Z9 60 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 7967 EP 7978 DI 10.1128/JVI.79.13.7967-7978.2005 PG 12 WC Virology SC Virology GA 936PA UT WOS:000229866700003 PM 15956543 ER PT J AU Schmitz, JE Johnson, RP McClure, HM Manson, KH Wyand, MS Kuroda, MJ Lifton, MA Khunkhun, RS McEvers, KJ Gillis, J Piatak, M Lifson, JD Grosschupff, G Racz, P Tenner-Racz, K Rieber, EP Kuus-Reichel, K Gelman, RS Letvin, NL Montefiori, DC Ruprecht, RM Desrosiers, RC Reimann, KA AF Schmitz, JE Johnson, RP McClure, HM Manson, KH Wyand, MS Kuroda, MJ Lifton, MA Khunkhun, RS McEvers, KJ Gillis, J Piatak, M Lifson, JD Grosschupff, G Racz, P Tenner-Racz, K Rieber, EP Kuus-Reichel, K Gelman, RS Letvin, NL Montefiori, DC Ruprecht, RM Desrosiers, RC Reimann, KA TI Effect of CD8(+) lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239 Delta 3-vaccinated rhesus macaques SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC-T-LYMPHOCYTE; HIV-1/SIV CHIMERIC VIRUS; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; PATHOGENIC SIVMAC239; VAGINAL CHALLENGE; MUCOSAL CHALLENGE; CELL DEPLETION; HIV VACCINES AB Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8(+) lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239 Delta 3 of CD8(+) lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8(+) lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8(+) cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01(+) major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8' T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01(-) animals. Consistent with these findings, the depletion of CD8' lymphocytes abrogated vaccine-induced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01(+) than in Manni-A*01(-) animals. The partial control of postchallenge viremia after CD8' lymphocyte depletion suggests that both Immoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined. C1 Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Primedica Corp, Worcester, MA 01536 USA. NCI, SAIC, AIDS Vaccine Program, Retroviral Pathogenesis Lab, Frederick, MD 21702 USA. Bernhard Nocht Inst Trop Med, Hamburg, Germany. Tech Univ Dresden, Inst Immunol, D-8027 Dresden, Germany. Beckman Ctr, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Schmitz, JE (reprint author), Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med, RE-113,330 Brookline Ave, Boston, MA 02215 USA. EM jschmitz@bidmc.harvard.edu FU NCI NIH HHS [N01-CO-124000]; NCRR NIH HHS [R24 RR016001, K26 RR000168, P51 RR000168, R01 RR014180, RR00168, RR13150, RR14180, RR16001]; NIAID NIH HHS [AI060354, AI062412, AI35365, AI48394, N01AI30034, P01 AI035365, P30 AI060354, R01 AI048394, R01 AI062412, U01 AI035365] NR 55 TC 98 Z9 98 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8131 EP 8141 DI 10.1128/JVI.79.13.8131-8141.2005 PG 11 WC Virology SC Virology GA 936PA UT WOS:000229866700018 PM 15956558 ER PT J AU Koibuchi, T Allen, TM Lichterfeld, M Mui, SK O'Sullivan, KM Trocha, A Kalams, SA Johnson, RP Walker, BD AF Koibuchi, T Allen, TM Lichterfeld, M Mui, SK O'Sullivan, KM Trocha, A Kalams, SA Johnson, RP Walker, BD TI Limited sequence evolution within persistently targeted CD8 Epitopes in chronic human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; ACTIVE ANTIRETROVIRAL THERAPY; LYMPHOCYTE RESPONSE; FINE SPECIFICITY; AUTOLOGOUS VIRUS; VIRAL LOAD; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; CONSERVED REGION; HIV-1 INFECTION AB Studies in acute human immunodeficiency virus type I (HIV-1) infection indicate viral evolution under CD8 T-cell immune selection pressure, but the effects of ongoing immune pressure on epitope evolution during chronic infection are not well described. In this study, we performed a detailed longitudinal analysis of viral sequence variation within persistently targeted cytotoxic T-lymphocyte (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent viremia. Responses were quantitated using freshly isolated peripheral blood lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma) Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in each person. In the majority of cases, the dominant epitope sequence did not change over time, even in the presence of responses of sufficient magnitude that they were detectable using fresh peripheral blood mononuclear cells in direct lytic assays. Only 4 of the 14 autologous epitopes tested represented potential CTL escape variants; however, in most cases strong responses to these epitopes persisted for the 6 years of study. Although persistent IFN-gamma responses were detected to all epitopes, direct lytic assays demonstrated declining responses to some epitopes despite the persistence of the targeted sequence in vivo. These data indicate limited viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Vanderbilt Univ, Infect Dis Unit, Dept Internal Med, Nashville, TN USA. Vanderbilt Univ, Infect Dis Unit, Dept Microbiol & Immunol, Nashville, TN USA. New England Primate Res Ctr, Southborough, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI39966, R01 AI028568, R01 AI039966, R01 AI28568] NR 48 TC 29 Z9 31 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 JUL PY 2005 VL 79 IS 13 BP 8171 EP 8181 DI 10.1128/JVI.79.13.8171-8181.2005 PG 11 WC Virology SC Virology GA 936PA UT WOS:000229866700022 PM 15956562 ER PT J AU Carnes, M Handelsman, J Sheridan, J AF Carnes, M Handelsman, J Sheridan, J TI Diversity in academic medicine: The stages of change model SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material ID SMOKING C1 Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. Univ Wisconsin, Dept Med, Madison, WI 53715 USA. Univ Wisconsin, WISELI, Madison, WI 53715 USA. Univ Wisconsin, Dept Plant Pathol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, Meriter Hosp 6 W,202 S Pk St, Madison, WI 53715 USA. EM mlcarnes@wisc.edu NR 18 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL PY 2005 VL 14 IS 6 BP 471 EP 475 DI 10.1089/jwh.2005.14.471 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 971SE UT WOS:000232404000005 PM 16115000 ER PT J AU Ward, WF Qi, WB Van Remmen, H Zackert, WE Roberts, LJ Richardson, A AF Ward, WF Qi, WB Van Remmen, H Zackert, WE Roberts, LJ Richardson, A TI Effects of age and caloric restriction on lipid peroxidation: Measurement of oxidative stress by F-2-isoprostane levels SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ADULT DROSOPHILA-MELANOGASTER; LIFE-SPAN; SUPEROXIDE-DISMUTASE; OVEREXPRESSION; ISOPROSTANES; EXPRESSION; INDUCTION; DISEASE; DAMAGE AB The free radical theory of aging proposes that the accumulation of oxidative damage is a key component of the aging process. The discovery of F-2-isoprostanes (F-2-isoPs) and their establishment as a sensitive and accurate biomarker of lipid peroxidation represents a major advance for measuring the oxidative stress status of an organism. We have shown that plasma free and total (free plus esterified) F-2-isoPs increase with age (185% and 66%, respectively), and that these increases are reduced by life-extending caloric restriction (50% and 23%, respectively). In addition, we found that levels of esterified F-2-isoPs increase 68% with age in liver, and 76% with age in kidney. Caloric restriction modulated the age-related increase, reducing the esterified F-2-isoPs levels 27% in liver and 35% in kidney. These age-related increases in esterified F-2-isoPs levels correlate well with DNA oxidation, as measured by 8-oxodeoxyguanosine production demonstrating that F-2-isoPs are an excellent biomarker for age-related changes in oxidative damage to membranes. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr & Res Serv, San Antonio, TX USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Ward, WF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, MSC-7756,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wardw@uthscsa.edu FU NIA NIH HHS [R01 AG23843, R01 AG025362-01]; NIGMS NIH HHS [R37 GM42053] NR 23 TC 72 Z9 73 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 847 EP 851 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900005 PM 16079206 ER PT J AU Moody-Ayers, SY Mehta, KM Lindquist, K Sands, L Covinsky, KE AF Moody-Ayers, SY Mehta, KM Lindquist, K Sands, L Covinsky, KE TI Black-white disparities in functional decline in older persons: The role of cognitive function SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med ID NORTH-CAROLINA EPESE; MINI-MENTAL-STATE; AFRICAN-AMERICAN; ALZHEIMER-DISEASE; UNITED-STATES; APOLIPOPROTEIN-E; TEST-PERFORMANCE; ELDERLY PERSONS; RISK; DISABILITY AB Background. Black elders have a greater frequency of functional decline than do white elders. The impact of cognitive function on explaining black-white disparities in functional decline has not been extensively explored. Methods. To compare the extent to which different risk domains (comorbidity, smoking, socioeconomic status (SES), self-rated health, and cognitive function) explain more frequent functional decline in black elders, we studied 779 black and 4892 white community-dwelling adults aged 70 and older from the Assets and Health Dynamics Among the Oldest Old (AHEAD), a population-based cohort study begun in 1993. Our primary outcome was worse functional status at 2 years than at baseline. We used logistic regression to compare the unadjusted with the adjusted black-white odds ratios (ORs) after adjusting for each risk domain. Results. At baseline black participants aged 70-79 had higher rates of smoking, diabetes, and hypertension; lower SES; and worse cognitive function than did white participants (p <.05 for all). The mean cognitive score was 15.7 in black and 21.8 in white participants (p <.01). Black participants had a higher frequency of 2-year functional decline than did white participants (10.9% vs 4.7%; OR = 2.61, 95% confidence interval [CI], 1.69-4.03 adjusted for age and sex). Adjustment for comorbidity and smoking did not significantly change the black-white OR, whereas self-rated health and SES accounted for about half the risk. Adjustment for cognitive function accounted for nearly all the associated decline (OR 1.10, 95% CI, 0.67-1.79). Among participants aged 80 and over, those who were black had significantly lower risk for functional decline after adjustment for cognitive function (OR = 0.61, 95% CI, 0.38-0.96 vs OR = 1.08, 95% CI, 0.70-1.66 adjusted for age and sex only). Conclusions. Cognitive function mediated the higher frequency of functional decline among black elders. Efforts to understand cognitive function may enhance our understanding of black-white disparities in health outcomes. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. RP Moody-Ayers, SY (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM sandra.moody@med.va.gov; covinsky@medicine.ucsf.edu RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU AHRQ HHS [K02HS000006-01]; NIA NIH HHS [1R01AG019827-01] NR 48 TC 33 Z9 33 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 933 EP 939 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900020 PM 16079221 ER PT J AU Yang, J Maarek, JMI Holschneider, DP AF Yang, J Maarek, JMI Holschneider, DP TI In vivo quantitative assessment of catheter patency in rats SO LABORATORY ANIMALS LA English DT Article DE indwelling catheters; catheter patency; fibrosis; steroids ID MUSCLE CELL-PROLIFERATION; CENTRAL VENOUS CATHETER; INTIMAL HYPERPLASIA; MYOINTIMAL HYPERPLASIA; JUGULAR-VEIN; VENA-CAVA; HEPARIN; BLOOD; DEXAMETHASONE; INHIBITION AB Formation of fibrin sleeves around catheter tips is a central factor in catheter failure during chronic implantation, and such tissue growth can occur despite administration of anticoagulants. We developed a novel method for monitoring catheter patency. This method recognizes the progressive nature of catheter occlusion, and tracks this process over time through measurement of changes in catheter resistance to a standardized 1 mL bolus infusion from a pressurized reservoir. Two indirect measures of catheter patency were used: (a) reservoir residual pressure and (b) reservoir discharge time. This method was applied to the study of catheter patency in rats comparing the effect of catheter material (silastic, polyurethane, Microrenathane(TM)), lock solution (heparin, heparin/dexamethasone) and two different cannulation sites (superior vena cava via the external jugular vein, inferior vena cava via the femoral vein). Our findings reveal that application of flexible smaller-size silastic catheters and a dexamethasone lock solution resulted in prolonged catheter patency. Patency could be maintained over nine weeks with the femoral vein catheters, compared with five weeks with the external jugular vein catheters. The current method for measuring catheter patency provides a useful index for the assessment of tissue growth around the catheter tip. The method also provides an objective and quantitative way of comparing changes in catheter patency for different surgical methods and catheter types. Our method improves on the conventional method of assessing catheter occlusion by judging the ability to aspirate from the catheter. C1 Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. Univ So Calif, Sch Engn, Dept Biomed Engn, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Holschneider, DP (reprint author), Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, 1333 San Pablo St,BMT 401,MC 9112, Los Angeles, CA 90089 USA. EM holshne@usc.edu FU NIBIB NIH HHS [R01 EB-00300-03, R01 EB000300] NR 37 TC 15 Z9 16 U1 1 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0023-6772 J9 LAB ANIM-UK JI Lab. Anim. PD JUL PY 2005 VL 39 IS 3 BP 259 EP 268 DI 10.1258/0023677054307033 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 946FR UT WOS:000230558300001 PM 16004684 ER PT J AU Prise, KM Schettino, G Folkard, M Held, KD AF Prise, KM Schettino, G Folkard, M Held, KD TI New insights on cell death from radiation exposure SO LANCET ONCOLOGY LA English DT Review ID CHARGED-PARTICLE MICROBEAM; DOSE HYPER-RADIOSENSITIVITY; DOUBLE-STRAND BREAKS; TARGETED CYTOPLASMIC IRRADIATION; INDUCED GENOMIC INSTABILITY; SISTER-CHROMATID EXCHANGES; LINEAR-ENERGY-TRANSFER; EARLY DNA-DAMAGE; ALPHA-PARTICLES; IONIZING-RADIATION AB Ionising radiation has been an important part of cancer treatment for almost a century, being used in external-beam radiotherapy, brachytherapy, and targeted radionuclide therapy. At the molecular and cellular level, cell killing has been attributed to deposition of energy from the radiation in the DNA within the nucleus, with production of DNA double-strand breaks playing a central part. However, this DNA-centric model has been questioned because cell-death pathways, in which direct relations between cell killing and DNA damage diverge, have been reported. These pathways include membrane-dependent signalling pathways and bystander responses (when cells respond not to direct radiation exposure but to the irradiation of their neighbouring cells). New insights into mechanisms of these responses coupled with technological advances in targeting of cells in experimental systems with microbeams have led to a reassessment of the model of how cells are killed by ionising radiation. This review provides an update on these mechanisms. C1 Mt Vernon Hosp, Gray Canc Inst, Northwood HA6 2JR, Middx, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Prise, KM (reprint author), Mt Vernon Hosp, Gray Canc Inst, POB 100, Northwood HA6 2JR, Middx, England. EM prise@gci.ac.uk RI Prise, Kevin/N-7872-2015; OI Prise, Kevin/0000-0001-6134-7946; Schettino, Giuseppe/0000-0003-3284-3953 FU NCI NIH HHS [P01 CA 095227] NR 89 TC 170 Z9 179 U1 2 U2 28 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2005 VL 6 IS 7 BP 520 EP 528 DI 10.1016/S1470-2045(05)70246-1 PG 9 WC Oncology SC Oncology GA 943PV UT WOS:000230367100022 PM 15992701 ER PT J AU Kirsch, DG Ebb, DH Hernandez, AH Tarbell, NJ AF Kirsch, DG Ebb, DH Hernandez, AH Tarbell, NJ TI Proton radiotherapy for Hodgkin's disease in the sacrum SO LANCET ONCOLOGY LA English DT Article ID RADIATION C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Paediat Haematol & Oncol, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ntarbell@partners.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2005 VL 6 IS 7 BP 532 EP 533 DI 10.1016/S1470-2045(05)70248-5 PG 2 WC Oncology SC Oncology GA 943PV UT WOS:000230367100024 PM 15992703 ER PT J AU Heaton, JT Kohler, JB Hillman, RE Zeitels, SM AF Heaton, JT Kohler, JB Hillman, RE Zeitels, SM TI A new instrument for intraoperative assessment of individual vocal folds SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY APR 30-MAY 01, 2004 CL Phoenix, AZ SP Amer Laryngol Assoc DE larynx; mucosal wave; phonosurgery; stroboscopy; vocal fold scarring; voice ID PHONATION THRESHOLD PRESSURE AB Objectives. Intraoperative assessment of vocal fold vibration during phonomicrosurgery performed under general anesthesia may enhance surgical decision-making. We therefore developed and bench-tested a new device we refer to as the aerodynamic vocal fold driver (AVFD). Materials and Methods: The AVFD comprises a hand-held probe that uses airflow to drive individual vocal folds into phonatory-like vibration. This permits stroboscopic visualization of mucosal waves with simultaneous control of subglottal air pressure. In initial experiments to validate the technique, AVFD driven phonation and conventional whole-larynx phonation were compared using excised canine larynges (n = 14). Results. Single vocal fold phonation using the AVFD and whole larynx phonation yielded similar, positive correlations between subglottal pressure and both amplitude and frequency of vibration. Experiments simulating vocal fold scar-related mucosal stiffening by subepithelial injection of fixative showed the expected elevation of phonation threshold pressures as measured with the AVFD. Likewise, unilateral tissue compression injury disrupted vocal fold vibration, and the AVFD was useful for quantifying improvement in the damaged vocal fold after repair with injection of cross-linked hyaluronic acid gel. Conclusions: These results show that this new instrument has the potential to provide novel and useful information for laryngeal experimentation and to improve phonosurgery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. RP Heaton, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM jheaton@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2005 VL 115 IS 7 BP 1223 EP 1229 DI 10.1097/01.MLG.0000163747.38402.78 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 943CM UT WOS:000230329600014 PM 15995511 ER PT J AU Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, N Richardson, P Figg, WD Anderson, KC AF Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, N Richardson, P Figg, WD Anderson, KC TI Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs SO LEUKEMIA LA English DT Article DE neoplasia; therapy; signal transduction; apoptosis; angiogenesis ID BONE-MARROW ANGIOGENESIS; MULTIPLE-MYELOMA CELLS; PROGNOSTIC VALUE; THERAPY; RESISTANCE; GROWTH AB Thalidomide alone or in combination with steroids has significant activity in multiple myeloma (MM). However, given its teratogenic potential, analogs have been synthesized, retaining the anti- MM activity without these side effects. We examined the anti- MM activity of two thalidomide analogs, CPS11 and CPS49. Direct cytotoxicity of the drugs on myeloma cell lines and patient myeloma cells was examined using thymidine uptake. Tumor cell apoptosis was evaluated by flow cytometry as well as Western blotting for caspase and PARP cleavage. Cellular signaling events were examined by immuno-blotting for phosphorylated proteins. Both drugs inhibit proliferation of several MM cell lines sensitive and resistant to conventional therapies. They decrease secretion of IL-6, IGF, and VEGF by marrow stromal cells. Importantly, they inhibit proliferation of MM cells adherent to stromal cells. These drugs induce caspase- mediated apoptosis in MM cell lines, as well as patient MM cells. They inhibit the PI3K/Akt and JAK/STAT (signal transducers and activators of transcription) pathways in MM cells and are antiangiogenic in matrigel- based assays. CPS11 and CPS49 have potent antimyeloma activity and can overcome protective effects of the tumor microenvironment. They have potent antiangiogenic activity and direct effect on bone marrow stroma. These encouraging preclinical data provide the basis for further evaluation in the clinic. C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Div Hematol, Rochester, MN USA. NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Anderson, KC (reprint author), Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, VA Boston Healthcare Syst, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008; Figg Sr, William/M-2411-2016; OI Kumar, Shaji/0000-0001-5392-9284; Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947]; PHS HHS [P0-78378] NR 20 TC 29 Z9 32 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 JUL PY 2005 VL 19 IS 7 BP 1253 EP 1261 DI 10.1038/sj.leu.2403776 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 937WR UT WOS:000229957400021 PM 15858615 ER PT J AU Lauer, GM AF Lauer, GM TI Hepatitis C virus-specific CD8(+) T cells restricted by donor HLA alleles following liver transplantation SO LIVER TRANSPLANTATION LA English DT Editorial Material ID IMMUNE-RESPONSES; INFECTION; TOLERANCE; ASSOCIATION; PERSISTENCE; ACTIVATION; ANTIGEN; ESCAPE AB By necessity, human liver transplantation is performed across HLA barriers. As a result, intracellular infection of the allograft presents a unique immunologic challenge for the recipient's immune system. In this study, we describe the presence of HLA-A2-restricted, hepatitis C virus (HCV)-specific CD8+ T cells in liver transplant recipients in whom the allograft is HLA-A2 positive and the recipient is HLA-A2 negative. These memory-effector T cells are recipient derived and recognize HCV peptide uniquely in the context of HLA-A2. Furthermore, these cells were absent before the transplant, suggesting that the allograft is capable of selectively expanding naive CD8+ T cells. The in vitro specificity to donor HLA allele-restricted CD8+ T cells suggests that these cells may function to control HCV spread in the allograft. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Lauer, GM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 19 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2005 VL 11 IS 7 BP 848 EP 850 DI 10.1002/lt.20423 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 940QH UT WOS:000230158500019 PM 15973724 ER PT J AU Belani, C von Pawel, J Pluzanska, A Gorbounova, V Kaukel, E Mattson, K Ramlau, R Fidias, P Millward, M Fossella, F AF Belani, C von Pawel, J Pluzanska, A Gorbounova, V Kaukel, E Mattson, K Ramlau, R Fidias, P Millward, M Fossella, F TI Phase III study of docetaxel-cisplatin (DC) or docetaxel-carboplatin (DCb) versus vinorelbine-cisplatin (VC) as first-line treatment of advanced non-small cell lung cancer (NSCLC): Analyses by gender SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Asklepios Fachkliniken Munchen Gauting, Gauting, Germany. M Kopernik Mem Hosp, Lodz, Poland. RAMS, Canc Res Ctr, Moscow, Russia. AK Hamburg Harbug, Hamburg, Germany. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Reg Lung Dis Ctr, Poznan, Poland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sydney Canc Ctr, Camperdown, NSW, Australia. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S235 EP S236 DI 10.1016/S0169-5002(05)80945-6 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801373 ER PT J AU Choi, NC Wolfgang, J Flarnpouri, S Patel, A Jiang, S Niernierko, A Chen, GTY AF Choi, NC Wolfgang, J Flarnpouri, S Patel, A Jiang, S Niernierko, A Chen, GTY TI 4D CT (computed tomography) improves TCP without an increase in NTCP of lung when compared with helical CT planning in 3D conformal radiation therapy (CRT) for patients with lung cancer SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 3 BP S25 EP S26 DI 10.1016/S0169-5002(05)80079-0 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NY UT WOS:000231308100017 ER PT J AU Earle, CC AF Earle, CC TI Reimbursement policies, research, and prescribing practices: The United States perspective SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 3 BP S31 EP S31 DI 10.1016/S0169-5002(05)80083-2 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NY UT WOS:000231308100021 ER PT J AU Eberhard, D Johnson, B Goddard, A Herbst, R Janne, P Johnson, D Klein, P Ostland, M Seshagiri, S Hillan, K AF Eberhard, D Johnson, B Goddard, A Herbst, R Janne, P Johnson, D Klein, P Ostland, M Seshagiri, S Hillan, K TI Mutation in EGFR, HER2, KRAS and BRAF in NSCLC: Prevalences and correlations with clinical outcomes in patients treated with carboplatin and paclitaxel with or without erlotinib SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Genentech Inc, San Francisco, CA 94080 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S62 EP S62 DI 10.1016/S0169-5002(05)80320-4 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800195 ER PT J AU Engelman, J Janne, R Mermel, C Pearlberg, J Mukohara, T Fleet, C Cichowski, K Johnson, B Cantley, L AF Engelman, J Janne, R Mermel, C Pearlberg, J Mukohara, T Fleet, C Cichowski, K Johnson, B Cantley, L TI ErbB-3 mediates PI3K activity in gefitinib-sensitive non-small cell lung cancer cell lines SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S108 EP S108 DI 10.1016/S0169-5002(05)80475-1 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800350 ER PT J AU Fanucchi, M Fossella, F Fidias, P Natale, R Belt, R Govindan, R Raez, L Schiller, J Kashala, O Kelly, K AF Fanucchi, M Fossella, F Fidias, P Natale, R Belt, R Govindan, R Raez, L Schiller, J Kashala, O Kelly, K TI Phase 2 study of bortezomib +/- docetaxel in advanced non-small cell lung cancer (NSCLC) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. Kansas City Oncol Hematol Grp, Kansas City, MO USA. Washington Univ, St Louis, MO USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S30 EP S30 DI 10.1016/S0169-5002(05)80217-X PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800092 ER PT J AU Hanna, N Bonomi, P Lynch, T Ansari, R Govindan, R Janne, R Lilenbaum, R AF Hanna, N Bonomi, P Lynch, T Ansari, R Govindan, R Janne, R Lilenbaum, R TI A phase II trial of cetuximab as therapy for recurrent non-small cell lung cancer (NSCLC) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Indiana Univ, Bloomington, IN 47405 USA. Rush Univ, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Michigan Hematol Oncol PC, South Bend, IN USA. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S38 EP S38 DI 10.1016/S0169-5002(05)80240-5 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800115 ER PT J AU Herbst, R Davies, A Johnson, B Natale, R Dang, T Murren, J Schiller, J Garland, L Miller, V Mendelson, D Melenevsky, Y Devries, D Van Den Abbeele, A Eberhard, D Lyons, B Lutzker, S AF Herbst, R Davies, A Johnson, B Natale, R Dang, T Murren, J Schiller, J Garland, L Miller, V Mendelson, D Melenevsky, Y Devries, D Van Den Abbeele, A Eberhard, D Lyons, B Lutzker, S TI Efficacy and safety of single agent pertuzumab (rhuMAb 2C4), a HER climerization inhibitor, in Non-Small Cell Lung Cancer (NSCLC) patients after prior chemotherapy SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 MD Anderson Canc Grp Houston, Houston, TX USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Cedars Sinai Canc Ctr, Los Angeles, CA 90048 USA. Vanderbilt Ingram Canc Ctr, Knoxville, TN USA. Yale Univ, Sch Med, Sect Med Oncol, New Haven, CT USA. Univ Wisconsin, Madison, WI USA. Arizona Canc Ctr, Tucson, AZ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Arizona Canc Ctr, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S62 EP S62 DI 10.1016/S0169-5002(05)80321-6 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800196 ER PT J AU Herbst, R Johnson, B Rowbottom, J Fidias, P Lu, C Prager, D Roubec, J Csada, E Dimery, I Heymach, J AF Herbst, R Johnson, B Rowbottom, J Fidias, P Lu, C Prager, D Roubec, J Csada, E Dimery, I Heymach, J TI ZD6474 plus docetaxel in patients with previously treated NSCLC: Results of a randomized, placebo-controlled Phase II trial SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN SP Int Assoc Study Lung Canc C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. AstraZeneca, Macclesfield, Cheshire, England. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Ostrava, Univ Hosp Ostrava, CZ-70852 Ostrava, Czech Republic. Univ Szeged, Szeged, Hungary. AstraZeneca, Wilmslow, Cheshire, England. NR 0 TC 22 Z9 26 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S35 EP S36 DI 10.1016/S0169-5002(05)80234-X PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800109 ER PT J AU Jackman, D Lucca, J Fidias, R Rabin, M Lynch, T Ostler, P Skarin, A Temel, J Johnson, B Janne, P AF Jackman, D Lucca, J Fidias, R Rabin, M Lynch, T Ostler, P Skarin, A Temel, J Johnson, B Janne, P TI Phase II study of the EGFR tyrosine kinase inhibitor erlotinib (Tarceva) in patients > 70 years of age with previously untreated advanced non-small cell lung carcinoma SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S62 EP S63 DI 10.1016/S0169-5002(05)80322-8 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800197 ER PT J AU Janne, P Simon, G Langer, C Taub, R Dowlati, A Fidias, P Bloss, L Ye, Z Obasaju, C Kindler, H AF Janne, P Simon, G Langer, C Taub, R Dowlati, A Fidias, P Bloss, L Ye, Z Obasaju, C Kindler, H TI An update of pemetrexed (P) plus gemcitabine (G) as front-line chemotherapy for patients (pts) with malignant pleural mesothelioma (MPM): A phase II clinical trial SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Oncol, Indianapolis, IN USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S282 EP S282 DI 10.1016/S0169-5002(05)81113-4 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802099 ER PT J AU Janne, R Sequist, L Lindeman, N Bell, D Huberman, M Meyerson, M Haber, D Lynch, T Johnson, B AF Janne, R Sequist, L Lindeman, N Bell, D Huberman, M Meyerson, M Haber, D Lynch, T Johnson, B TI Long-term survival of NSCLC patients with EGFR mutations treated with EGFR TKIs gefitinib or erlotinib SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S109 EP S109 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800353 ER PT J AU Kindler, H Lu, C Gandara, D Stevenson, J Krug, L Janne, P Gitlitz, B Karrison, T Stadler, W Vokes, E AF Kindler, H Lu, C Gandara, D Stevenson, J Krug, L Janne, P Gitlitz, B Karrison, T Stadler, W Vokes, E TI Gemcitabine/cisplatin plus bevacizumab or placebo in advanced malignant mesothelioma: A multi-center, double-blind, placebo-controlled, randomized phase III trial SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Chicago, Chicago, IL 60637 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Penn, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S28 EP S29 DI 10.1016/S0169-5002(05)80210-7 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800085 ER PT J AU Krug, L Pass, H Rusch, V Sugarbaker, D Rosenzweig, K Friedberg, J Bloss, L Obasaju, C Vogelzang, N AF Krug, L Pass, H Rusch, V Sugarbaker, D Rosenzweig, K Friedberg, J Bloss, L Obasaju, C Vogelzang, N TI A multicenter phase 2 trial of neo-adjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy (EPP) and radiation (RT) for malignant pleural mesothelioma (MPM) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Lilly Res Labs Inc, Indianapolis, IN USA. Nevada Canc Inst, Las Vegas, NV USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S223 EP S223 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801328 ER PT J AU Ma, P Dietrich, S Fox, E Naoki, K Schaefer, E Lader, A Richards, W Sugarbaker, D Jagadeeswaran, R Salgia, R AF Ma, P Dietrich, S Fox, E Naoki, K Schaefer, E Lader, A Richards, W Sugarbaker, D Jagadeeswaran, R Salgia, R TI Novel semaphorin- and juxtamembrane-domain mutations of c-MET in NSCLC: Potential for targeted inhibition SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Chicago, Canc Res Ctr, Pritzker Sch Med, Chicago, IL USA. Dana Farber Canc Inst, Dept Mol Diagnost, Boston, MA 02115 USA. Yokohama Municipal Citizens Hosp, Yokohama, Kanagawa, Japan. BioSource Int Inc, Camarillo, CA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RI Jagadeeswaran, Ramasamy/C-9987-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S64 EP S65 DI 10.1016/S0169-5002(05)80328-9 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800203 ER PT J AU Merrick, D Winterhalder, R Kittelson, J Franklin, W Kotantoulas, G Ingeberg, S Miller, Y Hirsch, F AF Merrick, D Winterhalder, R Kittelson, J Franklin, W Kotantoulas, G Ingeberg, S Miller, Y Hirsch, F TI Increased expression of C-erb-B1 (EGF-R) but not C-erb-B2 (HER2) is associated with dysplastic change in bronchial airways: Correlation with increased Ki67, MCM2 and P53 expression SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S83 EP S83 DI 10.1016/S0169-5002(05)80390-3 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800265 ER PT J AU Merrick, D Sugita, M Hirsch, F Keith, R Miller, Y Coldren, C Lapadat, R Witta, S Geraci, M Franklin, W AF Merrick, D Sugita, M Hirsch, F Keith, R Miller, Y Coldren, C Lapadat, R Witta, S Geraci, M Franklin, W TI Affymetrix gene expression profiles in premalignant bronchial mucosa SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S19 EP S20 DI 10.1016/S0169-5002(05)80181-3 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800056 ER PT J AU Miller, Y Keith, R Hirsch, F Dempsey, E Franklin, W Kennedy, T AF Miller, Y Keith, R Hirsch, F Dempsey, E Franklin, W Kennedy, T TI Natural history of untreated endobronchial carcinoma in situ SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S184 EP S184 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801187 ER PT J AU Miller, Y Hyun, D Blatchford, P Lewis, M Keith, R Kennedy, T Franklin, W Kittelson, J Hirsch, F AF Miller, Y Hyun, D Blatchford, P Lewis, M Keith, R Kennedy, T Franklin, W Kittelson, J Hirsch, F TI Ki67 proliferation index in endbronchial biopsies: Association with lung cancer, airflow obstruction and smoking history SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Colorado, Ctr Canc, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S183 EP S184 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801186 ER PT J AU Mukohara, T Engelman, J Lindeman, N Pearlberg, J Cantley, L Johnson, B Janne, P AF Mukohara, T Engelman, J Lindeman, N Pearlberg, J Cantley, L Johnson, B Janne, P TI Differential effects of gefitinib and cetuximab on EGFR mutant non-small cell lung cancers (NSCLC) cell lines SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S7 EP S7 DI 10.1016/S0169-5002(05)80141-2 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800016 ER PT J AU Pandya, K Levy, D Hidalgo, M Cohen, R Lee, M Dancey, J Schiller, J Johnson, D AF Pandya, K Levy, D Hidalgo, M Cohen, R Lee, M Dancey, J Schiller, J Johnson, D TI A randomized phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small cell lung cancer in remission after induction therapy SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Rochester, Rochester, NY 14627 USA. Dana Farber Canc Inst, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. Vanderbilt Univ, Nashville, TN 37240 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S54 EP S54 DI 10.1016/S0169-5002(05)80292-2 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800167 ER PT J AU Patel, J Gray, R Stewart, J Skinner, H Schiller, J AF Patel, J Gray, R Stewart, J Skinner, H Schiller, J TI The anti-estrogen tamoxifen has no impact of the risk of lung cancer in women SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Madison, WI USA. Northwestern Univ, Chicago, IL 60611 USA. RI Skinner, Halcyon/A-1049-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S195 EP S195 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801225 ER PT J AU Pirl, W Temel, J Cashavelly, B Lynch, T AF Pirl, W Temel, J Cashavelly, B Lynch, T TI Validity of one-item scale for rapid screening of fatigue in thoracic oncology patients SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S56 EP S57 DI 10.1016/S0169-5002(05)80300-9 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800175 ER PT J AU Richards, W Zellos, L Bueno, R Jaklitsch, M Wright, J Tretyakov, O Hartigan, P FitzGerald, D Frei, E Sugarbaker, D AF Richards, W Zellos, L Bueno, R Jaklitsch, M Wright, J Tretyakov, O Hartigan, P FitzGerald, D Frei, E Sugarbaker, D TI A Phase I trial of extrapleural pneumonectomy and intraoperative, bicavitary, hyperthermic cisplatin lavage with intravenous sodium thiosulfate protection for patients with malignant pleural mesothelioma SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S228 EP S228 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801346 ER PT J AU Rizvi, N Villalona-Calero, M Lynch, T Yee, L Gabrail, N Sandler, A Cropp, G Graham, M Palmer, G AF Rizvi, N Villalona-Calero, M Lynch, T Yee, L Gabrail, N Sandler, A Cropp, G Graham, M Palmer, G TI A Phase II study of KOS-862 (Epothilone D) as second-line therapy in non-small cell lung cancer SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Kosan Biosci Inc, Hayward, CA USA. Ohio State Univ, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NW Med Specialists, Tacoma, WA USA. Gabrail Canc Ctr, Canton, OH USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S267 EP S267 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802044 ER PT J AU Sandler, A Kris, M Miller, V Carbone, D Pao, W Billheimer, D Tsao, A Patel, J Johnson, B Johnson, D AF Sandler, A Kris, M Miller, V Carbone, D Pao, W Billheimer, D Tsao, A Patel, J Johnson, B Johnson, D TI Phase II trial of erlotinib in patients with bronchioloalveolar carcinoma SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S38 EP S39 DI 10.1016/S0169-5002(05)80243-0 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800118 ER PT J AU Sandler, AB Gray, R Brahmer, J Dowlati, A Schiller, JH Perry, MC Johnson, DH AF Sandler, AB Gray, R Brahmer, J Dowlati, A Schiller, JH Perry, MC Johnson, DH TI Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC #704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) trial - E4599 SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Wisconsin, Madison, WI USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. RI Johnson, David/A-7437-2009 NR 0 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S31 EP S31 DI 10.1016/S0169-5002(05)80220-X PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800095 ER PT J AU Sequist, L Fidias, P Temel, J Kennedy, E Ostler, P Rabin, M Huberman, M Keck, J Brown, G Lynch, T AF Sequist, L Fidias, P Temel, J Kennedy, E Ostler, P Rabin, M Huberman, M Keck, J Brown, G Lynch, T TI Phase I-II trial of TLK286 (telcyta), carboplatin (C), and paclitaxel (P) as first-line treatment for advanced non-small cell lung cancer (NSCLC) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Telik Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S269 EP S269 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802051 ER PT J AU Sequist, L Janne, P Joshi, V Fidias, P Verlander, P Meyerson, M Haber, D Johnson, B Kucherlapati, R Lynch, T AF Sequist, L Janne, P Joshi, V Fidias, P Verlander, P Meyerson, M Haber, D Johnson, B Kucherlapati, R Lynch, T TI The Massachusetts General Hospital/Dana-Farber Cancer Institute/Harvard Medical School partners Healthcare center for genetics and genomics experience with clinical testing for somatic EGFR mutations in NSCLC patients SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners HealthCare Ctr Genet & Genom, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S112 EP S112 DI 10.1016/S0169-5002(05)80489-1 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800364 ER PT J AU Shigematsu, H Nomura, M Suzuki, M Lee, H Wistuba, I Fong, K Toyooka, S Shimizu, N Minna, J Gazdar, A AF Shigematsu, H Nomura, M Suzuki, M Lee, H Wistuba, I Fong, K Toyooka, S Shimizu, N Minna, J Gazdar, A TI Gene mutations indicate different pathways to lung cancers in never and ever smokers SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S7 EP S8 DI 10.1016/S0169-5002(05)80143-6 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800018 ER PT J AU Temel, J Jackson, V Billings, A Dahlin, C Fidias, P Buss, M Block, S Ostler, P Kornblith, A Lynch, T AF Temel, J Jackson, V Billings, A Dahlin, C Fidias, P Buss, M Block, S Ostler, P Kornblith, A Lynch, T TI Early palliative care (EPC) in patients with advanced non-small cell lung cancer (NSCLC) is feasible SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S342 EP S342 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802326 ER PT J AU Temel, J Pirl, W Cashavelly, B Lynch, T AF Temel, J Pirl, W Cashavelly, B Lynch, T TI Fatigue screening in a thoracic oncology clinic SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S342 EP S342 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802325 ER PT J AU Wakelee, H Wang, W Schiller, J Langer, C Sandler, A Belani, C Johnson, D AF Wakelee, H Wang, W Schiller, J Langer, C Sandler, A Belani, C Johnson, D TI Survival differences by gender for patients with advanced non-small cell lung cancer in Eastern Cooperative Oncology Group trial 1594 SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Stanford Univ, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Madison, WI USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Vanderbilt Univ, Nashville, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S22 EP S22 DI 10.1016/S0169-5002(05)80188-6 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800063 ER PT J AU Burns, MA Taylor, JL Wu, CL Zepeda, AG Bielecki, A Cory, D Cheng, LL AF Burns, MA Taylor, JL Wu, CL Zepeda, AG Bielecki, A Cory, D Cheng, LL TI Reduction of spinning sidebands in proton NMR of human prostate tissue with slow high-resolution magic angle spinning SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE HRMAS; proton MRS; human prostate; slow spinning; pathology ID MAGNETIC-RESONANCE SPECTROSCOPY; H-1-NMR SPECTROSCOPY; CARTILAGE; TOXICITY; CANCER; TUMORS AB High-resolution magic angle spinning (HRMAS) NMR spectroscopy has proven useful for analyzing intact tissue and permitting correlations to be made between tissue metabolites and disease pathologies. Extending these studies to slow-spinning methodologies helps protect tissue pathological structures from HRMAS centrifuging damage and may permit the study of larger objects. Spinning sidebands (SSBs), which are produced by slow spinning, must be suppressed to prevent the complication of metabolic spectral regions. In this study human prostate tissues, as well as gel samples of a metabolite mixture solution, were measured with continuous-wave (CW) water pre-saturation on a 14.1T spectrometer, with HRMAS spinning rates of 250, 300, 350, 600, and 700 Hz, and 3.0 kHz. Editing the spectra by means of a simple minimum function (Min(A, B,..., N) for N spectra acquired at different but close spinning rates) produced SSB-free spectra. Statistically significant linear correlations were observed for metabolite concentrations quantified from the Min(A, B,..., N)-edited spectra generated at low spinning rates, with concentrations measured from the 3 kHz spectra, and also with quantitative pathology. These results indicate the empirical utility of this scheme for analyzing intact tissue, which also may be used as an adjunct tool in pathology for diagnosing disease. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. MIT, Francis Bitter Magnet Lab, Cambridge, MA USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. RP Cheng, LL (reprint author), Pathol Res, CNY-7,149 13th St, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu FU NCI NIH HHS [CA095624, CA77727, CA80901]; NIBIB NIH HHS [EB002026] NR 17 TC 20 Z9 20 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUL PY 2005 VL 54 IS 1 BP 34 EP 42 DI 10.1002/mrm.20523 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 938OX UT WOS:000230013800006 PM 15968646 ER PT J AU Wiggins, GC Potthast, A Triantafyllou, C Wiggins, CJ Wald, LL AF Wiggins, GC Potthast, A Triantafyllou, C Wiggins, CJ Wald, LL TI Eight-channel phased array coil and detunable TEM volume coil for 7 T brain imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE phased array; 7 T; RF coil design; SNR; high field MRI ID HIGH-FIELD; SURFACE COIL; HEAD; NMR; POWER; TESLA AB An eight-channel receive-only brain coil and table-top detunable volume transmit coil were developed and tested at 7 T for human imaging. Optimization of this device required attention to sources of interaction between the array elements, between the transmit and receive coils and minimization of common mode currents on the coaxial cables. Circular receive coils (85 mm dia.) were designed on a flexible former to fit tightly around the head and within a 270-mm diameter TEM transmit volume coil. In the near cortex, the array provided a fivefold increase in SNR compared to a TEM transmit-receive coil, a gain larger than that seen in comparable coils at 3 T. The higher SNR gain is likely due to strong dielectric effects, which cause the volume coil to perform poorly in the cortex compared to centrally. The sensitivity and coverage of the array is demonstrated with high-resolution images of the brain cortex. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Dept Radiol, AA Martinos Ctr, Charlestown, MA USA. Siemens Med Syst Inc, Erlangen, Germany. RP Wiggins, GC (reprint author), Ctr Biomed Imaging, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM gwiggins@nmr.mgh.harvard.edu RI Triantafyllou, Christina/E-7724-2011; Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [5P41RRO14075-05] NR 18 TC 46 Z9 46 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUL PY 2005 VL 54 IS 1 BP 235 EP 240 DI 10.1002/mrm.20547 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 938OX UT WOS:000230013800033 PM 15968650 ER PT J AU Aspinall, SL Good, CB Glassman, PA Valentino, MA AF Aspinall, SL Good, CB Glassman, PA Valentino, MA TI The evolving use of cost-effectiveness analysis in formulary management within the Department of Veterans Affairs SO MEDICAL CARE LA English DT Article DE cost-effectiveness analysis; formulary management; pharmacy benefits management; drug use evaluation ID CORONARY-HEART-DISEASE; PULMONARY-ARTERIAL-HYPERTENSION; AVERAGE CHOLESTEROL LEVELS; PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; SUBCUTANEOUS INFUSION; MULTIPLE-SCLEROSIS; EVENTS; PREVENTION; PRAVASTATIN AB The Veterans Health Administration (VHA) runs the largest integrated healthcare system in the nation. Formulary management within VHA primarily involves 3 national groups: the Medical Advisory Panel, the Veterans Integrated Service Network Formulary Leaders, and the Pharmacy Benefits Management Strategic Healthcare Group. Together, these groups manage the VHA national drug formulary with a goal of providing a comprehensive, safe, and cost-effective pharmacy benefit for veterans. Traditionally, VHA has relied on cost-minimization analyses in formulary decisions. More recently, VHA has emphasized the use of cost-effectiveness data, especially for newer, costly drugs. In addition to including this data in drug monographs, the VHA has begun requiring formal cost-effectiveness analysis from manufacturers of selected pharmaceuticals. VHA has also requested that clinically relevant information such as quality of life plus mortality benefit be made available from industry so that internal cost analyses can be performed. It is hoped that by setting the expectation that cost-effectiveness will be formally considered in all VHA formulary decisions, the pharmaceutical industry and others will be stimulated to collect and report data that enables these analyses. We believe that if other organizations also place an emphasis on economic evaluations, industry and the public will be more accepting of decisions that incorporate cost considerations. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. VA Greater Los Angeles Healthcare Syst W LA, Div Gen Internal Med 111G, Los Angeles, CA USA. Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Hines, IL USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151-C, Pittsburgh, PA 15240 USA. EM Sherrie.Aspinall@med.va.gov NR 36 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2005 VL 43 IS 7 SU S BP 20 EP 26 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 942ZX UT WOS:000230322500004 PM 16056005 ER PT J AU Helfand, M AF Helfand, M TI Incorporating information about cost-effectiveness into evidence-based decision-making - The Evidence-Based Practice Center (EPC) model SO MEDICAL CARE LA English DT Article DE cost effectiveness; evidence-based medicine; decision making ID SERVICES-TASK-FORCE; PREVENTIVE-SERVICES; ECONOMIC EVALUATIONS; THYROID-DISEASE; TRIALS; RECOMMENDATIONS; GUIDELINES; MANAGEMENT; DYSPEPSIA; REVIEWS AB Rationale: There is a pressing need for guidance on how to incorporate economic information into evidence-based decision-making. Such guidance should take account of the quality and relevance of economic evaluations. Objective: To summarize lessons learned in integrating information from decision analyses and cost-effectiveness analyses. Key Issues: Several methods used by the Evidence-Based Practice Centers (EPCs) to conduct systematic reviews are applicable to assessing economic studies. We discuss methods to identify key questions for the review of economic studies. Reviews should assess how an economic model incorporates clinical logic and handles uncertainty about effectiveness. As is the case for metaanalysis of interventions, qualitative or quantitative synthesis of economic studies should explore heterogeneity to identify key uncertainties underlying divergent results as well as unsuspected sources of bias. Conclusions: Applying EPC methods to synthesis of economic information can increase their relevance to clinicians and policy-makers and inform decisions that require tradeoffs between effectiveness and harms of interventions. C1 Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. RP Helfand, M (reprint author), Portland VA Med Ctr, Dept Hosp & Specialty Med, P3-MED,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM helfand@ohsu.edu NR 38 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2005 VL 43 IS 7 SU S BP 33 EP 43 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 942ZX UT WOS:000230322500006 PM 16056007 ER PT J AU Asch, SM Baker, DW Keesey, JW Broder, M Schonlau, M Rosen, M Wallace, PL Keeler, EB AF Asch, SM Baker, DW Keesey, JW Broder, M Schonlau, M Rosen, M Wallace, PL Keeler, EB TI Does the collaborative model improve care for chronic heart failure? SO MEDICAL CARE LA English DT Article DE quality improvement; collaboratives; congestive heart failure ID CONTINUOUS QUALITY IMPROVEMENT; CHRONIC ILLNESS; DISEASE MANAGEMENT; PERFORMANCE; ENALAPRIL; INTERVENTIONS; IMPACT; LIFE AB Background: Organizationally based, disease-targeted collaborative quality improvement efforts are widely applied but have not been subject to rigorous evaluation. We evaluated the effects of the Institute of Healthcare Improvement's Breakthrough Series (IHI BTS) on quality of care for chronic heart failure (CHF). Research Design: We conducted a quasi-experiment in 4 organizations participating in the IHI BTS for CHF in 1999-2000 and 4 comparable control organizations. We reviewed a total of 489 medical records obtained from the sites and used a computerized data collection tool to measure performance on 23 predefined quality indicators. We then compared differences in indicator performance between the baseline and postintervention periods for participating and nonparticipating organizations. Results: Participating and control patients did not differ significantly with regard to measured clinical factors at baseline. After adjusting for age, gender, number of chronic conditions, and clustering by site, participating sites showed greater improvement than control sites for I I of the 21 indicators, including use of lipid-lowering and angiotensin converting enzyme inhibition therapy. When all indicators were combined into a single overall process score, participating sites improved more than controls (17% versus 1%, P < 0.0001). The improvement was greatest for measures of education and counseling (24% versus -1%, P < 0.0001). Conclusions: Organizational participation in a common disease-targeted collaborative provider interaction improved a wide range of processes of care for CHF, including both medical therapeutics and education and counseling. Our data support the use of programs like the IHI BTS in improving the processes of care for patients with chronic diseases. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. Northwestern Univ, Feinberg Sch Med, Inst Hlth Serv & Policy Res, Div Gen Internal Med, Chicago, IL 60611 USA. Zynx, Los Angeles, CA USA. RP Asch, SM (reprint author), 11301 Wilshire Blvd,Mailstop 111G, Los Angeles, CA 90073 USA. EM sasch@rand.org NR 36 TC 42 Z9 42 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2005 VL 43 IS 7 BP 667 EP 675 DI 10.1097/01.mlr.0000167182.72251.a1 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 940QJ UT WOS:000230158700005 PM 15970781 ER PT J AU Cargill, VA Stone, VE AF Cargill, VA Stone, VE TI HIV/AIDS: A minority health issue SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; AIDS CLINICAL-TRIALS; PROTEASE INHIBITORS; P-GLYCOPROTEIN; DRUG-USERS; ANTIRETROVIRAL THERAPY; AFRICAN-AMERICANS; UNITED-STATES; SERVICE USE AB HIV infection disproportionately affects racial and ethnic minority populations in the United States. The reasons for this disproportionate impact are complex, and intertwined with many confounding issues that also disproportionately affect racial and ethnic minorities. Superimposed on these factors are the unique cultural beliefs and contexts that influence behavior, health beliefs in general, and HIV infection in particular. As the epidemic continues in these communities, presentations of plicated by the presence of other chronic portionate in these communities, Failure broad-based prevention interventions for ties virtually ensures that HIV transmission in communities already severely affected. HIV infection are diseases that are disproportionate to achieve successful racial and ethnic minorities virtually ensures that HIV transmission will continue unabated in communities already severely affected. C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Cargill, VA (reprint author), NIH, Off AIDS Res, 2 Ctr Dr,Room 4E20, Bethesda, MD 20892 USA. EM vc52x@nih.gov NR 70 TC 70 Z9 71 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2005 VL 89 IS 4 BP 895 EP + DI 10.1016/j.mcna.2005.03.005 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 938WU UT WOS:000230034900011 PM 15925655 ER PT J AU Boas, D AF Boas, D TI Diffuse optical imaging of the neuro-metabolic-vascular relationship during brain activation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 51st Annual Meeting of the Canadian-Organization-of-Medical-Physicists/Canadian-College-of-Physicis ts-in-Medicine CY JUL 07-09, 2005 CL McMaster Univ, Hamilton, CANADA SP Canadian Org Med Phys, Canadian Coll Phys Med HO McMaster Univ C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2005 VL 32 IS 7 BP 2407 EP 2407 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 945ZW UT WOS:000230542600030 ER PT J AU Giannopoulou, I Fernhall, B Carhart, R Weinstock, RS Baynard, T Figueroa, A Kanaley, JA AF Giannopoulou, I Fernhall, B Carhart, R Weinstock, RS Baynard, T Figueroa, A Kanaley, JA TI Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID C-REACTIVE PROTEIN; SERUM LEPTIN LEVELS; PLASMA RESISTIN CONCENTRATIONS; REVERSES INSULIN-RESISTANCE; SUBCUTANEOUS ADIPOSE-TISSUE; LINKED-IMMUNOSORBENT-ASSAY; NECROSIS-FACTOR-ALPHA; WEIGHT-LOSS; OBESE WOMEN; METABOLIC SYNDROME AB This study examined the independent and combined effects of diet and exercise on adipocytokine and inflammatory cytokines in postmenopausal women with type 2 diabetes. Using a randomized, controlled design, 33 women (age, 50-70 years) were assigned to diet alone (D), exercise alone (EX), or diet + exercise (D + E) for 14 weeks. Before and after the interventions, blood samples for adipocytokines and inflammatory markers were drawn, a meal test was performed, and abdominal fat distribution was measured by magnetic resonance imaging (MRI). Body weight decreased similar to 4.5 +/- 0.6 kg (P <.05) after the D and D + E interventions, whereas only small changes in body weight were found with the exercise-alone intervention. Plasma C-reactive protein levels were decreased by -15% with all 3 interventions, whereas leptin levels were reduced with the D and D + E intervention (1): pre = 48.7 +/- 6.0, post = 38.9 +/- 5.0 ng/mL; D + E: pre = 38.5 +/- 6.0, post = 22.9 +/- 5.0 ng/mL; P <.05) with no differences between groups. There was a trend for leptin levels to decrease in the EX group (P =.06). Plasma resistin levels were not altered by the 3 interventions from pre- to posttreatment (1): pre = 6.9 +/- 0.6, post = 6.2 +/- 0.4 ng/mL; D + E: pre = 5.6 +/- 0.6, post = 5.7 +/- 0.4 ng/mL; E: pre = 6.2 +/- 0.6, post = 5.9 +/- 0.6 ng/mL, P >.05), and no differences in adiponectin and tumor necrosis factor alpha (TNF-alpha) levels were found. Visceral adipose tissue and tumor necrosis factor a were the only predictors of calculated insulin resistance (P <.05), explaining 43% of the variability. A typically prescribed weight loss program with lifestyle changes resulted in few changes in adipocytokines and inflammatory cytokines in older women with type 2 diabetes, suggesting that dramatic weight loss or clinical interventions are needed. (c) 2005 Elsevier Inc. All rights reserved. C1 Syracuse Univ, Dept Exercise Sci, Syracuse, NY 13244 USA. SUNY Upstate Med Univ, Dept Cardiol, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Med, Joslin Diabet Ctr, Syracuse, NY 13210 USA. Vet Adm Med Ctr, Dept Med, Syracuse, NY 13210 USA. RP Kanaley, JA (reprint author), Syracuse Univ, Dept Exercise Sci, Syracuse, NY 13244 USA. EM jakanale@syr.edu OI Baynard, Tracy/0000-0002-5150-4095 NR 65 TC 100 Z9 104 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2005 VL 54 IS 7 BP 866 EP 875 DI 10.1016/j.metabol.2005.01.033 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 942KS UT WOS:000230281900005 PM 15988694 ER PT J AU Copeland, LA Fletcher, CE Patterson, JE AF Copeland, LA Fletcher, CE Patterson, JE TI Veterans' health and access to care in the year after September 11, 2001 SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT AcademyHealth Annual Meeting CY JUN, 2004 CL San Diego, CA ID TERRORIST ATTACKS; SURVEY SF-36; SELECTION; SERVICES; STRESS; CITY AB Objective: The goal was to explore veterans' perceptions of their health care in the year after September 11, 2001. Methods: A random sample of outpatients seen at a Manhattan (New York City) or Midwestern Veterans Affairs facility between September 12, 2001, and September 30, 2002, received a mailed questionnaire. Regression assessed the effects of site, demographic features, military service, and symptoms of post-traumatic stress disorder (PTSD) on health status, care-seeking, and satisfaction with health care among 490 patients. Results: Veterans from New York City reported better health and more satisfaction that their providers listened to them. Patients with more PTSD symptoms reported poorer health, more September 11-related symptoms, and less satisfaction with care and were more likely to seek care outside the Veterans Affairs system. Conclusions: Proximity to the September 11 terrorist attacks had little relationship to patients' perceptions of their health and health care, whereas PTSD symptoms had a pervasive effect. Patients with PTSD symptoms may require out-reach programs to assist them in dealing with catastrophic events, regardless of their proximity to the events. C1 VA Ann Arbor Healthcare Syst, Dev Ctr Excellence, Ann Arbor, MI 48105 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv Res, Ann Arbor, MI 48105 USA. VA New York Harbor Healthcare Syst Ctr, Dept Psychol, Brooklyn, NY 11209 USA. RP Copeland, LA (reprint author), S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX 78229 USA. OI Copeland, Laurel/0000-0002-9478-0209 NR 20 TC 3 Z9 3 U1 1 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2005 VL 170 IS 7 BP 602 EP 606 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 019JN UT WOS:000235831500011 PM 16130642 ER PT J AU Qa'dan, M Christensen, KA Zhang, L Roberts, TA Collier, RJ AF Qa'dan, M Christensen, KA Zhang, L Roberts, TA Collier, RJ TI Membrane insertion by anthrax protective antigen in cultured cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LETHAL FACTOR; ADENYLATE-CYCLASE; DEPENDENT PROCESS; MAMMALIAN-CELLS; TOXIN RECEPTOR; EDEMA FACTOR; N-TERMINUS; TRANSLOCATION; IDENTIFICATION; MACROPHAGES AB The enzymatic moieties of anthrax toxin enter the cytosol of mammalian cells via a pore in the endosomal membrane formed by the protective antigen (PA) moiety. Pore formation involves an acidic pH-induced conformational rearrangement of a heptameric precursor (the prepore), in which the seven 2 beta 2-2 beta 3 loops interact to generate a 14-strand transmembrane P-barrel. To investigate this model in vivo, we labeled PA with the fluorophore 7-nitrobenz-2-oxa-1,3-diazole (NBD) at cysteine residues introduced into the 2 beta 2-2 beta 3 loop. Each labeled PA was bound to CHO cells, and NBD fluorescence was monitored over time in stirred cell suspensions or by confocal microscopy. A strong increase was observed with NBD at positions 305, 307, 309, and 311, sites where side chains are predicted to face the bilayer, and little change was seen at residues 304, 306, 308, 310, and 312, sites where side chains are predicted to face the pore lumen. The increase at position 305 was inhibited by membrane-restricted quenchers, low temperature, or various reagents known to affect toxin action. Of the 24 NBD attachment sites examined, all but three gave results qualitatively consistent with the P-barrel model. Besides supporting the P-barrel model of membrane insertion, our results describe the time course of insertion and identify PA residues where NBD gives a strong signal upon membrane insertion in vivo. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Collier, RJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM jcollier@hms.harvard.edu RI Christensen, Kenneth/A-3235-2009; Christensen, Kenneth/D-3460-2017; OI Collier, R John/0000-0002-2427-4239 FU NIAID NIH HHS [AI22021, R01 AI022021, R37 AI022021] NR 34 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 13 BP 5492 EP 5498 DI 10.1128/MCB.25.13.5492-5498.2005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 937IX UT WOS:000229918900017 PM 15964805 ER PT J AU Skaar, JR Arai, T DeCaprio, JA AF Skaar, JR Arai, T DeCaprio, JA TI Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EARLY EMBRYONIC LETHALITY; SCF UBIQUITIN LIGASE; CYCLIN-E; MDM2-DEFICIENT MICE; MAMMALIAN-CELLS; PROTEINS; COMPLEX; P53; DOMAIN; GENE AB CUL7, a recently identified member of the cullin family of E3 ubiquitin ligases, forms a unique SCF-like complex and is required for mouse embryonic development. To further investigate CUL7 function, we sought to identify CUL7 binding proteins. The p53-associated, parkin-like cytoplasmic protein (PARC), a homolog of CUL7, was identified as a CUL7-interacting protein by mass spectrometry. The heterodimerization of PARC and CUL7, as well as homodimerization of PARC and CUL7, was confirmed in vivo. To determine the biological role of PARC by itself and in conjunction with CUL7, a targeted deletion of Pare was created in the mouse. In contrast to the neonatal lethality of the Cul7 knockout mice, Parc knockout mice were born at the expected Mendelian ratios and exhibited no apparent phenotype. Additionally, Pare deletion did not appear to affect the stability or function of p53. These results suggest that PARC and CUL7 form an endogenous complex and that PARC and CUL7 functions are at least partially nonoverlapping. In addition, although PARC and p53 form a complex, the absence of effect of Pare deletion on p53 stability, localization, and function suggests that p53 binding to PARC may serve to control PARC function. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer Bldg 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01 CA093804, R01CA93804] NR 35 TC 19 Z9 22 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 13 BP 5579 EP 5589 DI 10.1128/mcb.25.13.5579-5589.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 937IX UT WOS:000229918900025 PM 15964813 ER PT J AU Sofer, A Lei, K Johannessen, CM Ellisen, LW AF Sofer, A Lei, K Johannessen, CM Ellisen, LW TI Regulation of mTOR and cell growth in response to energy stress by REDD1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR COMPLEX; TOP MESSENGER-RNAS; TRANSLATION INITIATION; RPS6 PHOSPHORYLATION; 3-KINASE/AKT PATHWAY; SIGNALING PATHWAY; CYCLE PROGRESSION; MAMMALIAN TARGET; HUMAN-DISEASE AB The tuberous sclerosis tumor suppressors TSC1 and TSC2 regulate the mTOR pathway to control translation and cell growth in response to nutrient and growth factor stimuli. We have recently identified the stress response REDD1 gene as a mediator of tuberous sclerosis complex (TSC)-dependent mTOR regulation by hypoxia. Here, we demonstrate that REDD1 inhibits mTOR function to control cell growth in response to energy stress. Endogenous REDD1 is induced following energy stress, and REDD1(-/-) cells are highly defective in dephosphorylation of the key mTOR substrates S6K and 4E-BP1 following either ATP depletion or direct activation of the AMP-activated protein kinase (AMPK). REDD1 likely acts on the TSC1/2 complex, as regulation of mTOR substrate phosphorylation by REDD1 requires TSC2 and is blocked by overexpression of the TSC1/2 downstream target Rheb but is not blocked by inhibition of AMPK. Tetracycline-inducible expression of REDD1 triggers rapid dephosphorylation of S6K and 4E-BP1 and significantly decreases cellular size. Conversely, inhibition of endogenous REDD1 by short interfering RNA increases cell size in a rapamycin-sensitive manner, and REDD1(-/-) cells are defective in cell growth regulation following ATP depletion. These results define REDD1 as a critical transducer of the cellular response to energy depletion through the TSC-mTOR pathway. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA122589] NR 58 TC 230 Z9 239 U1 2 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 14 BP 5834 EP 5845 DI 10.1128/MCB.25.14.5834-5845.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942EZ UT WOS:000230267000005 PM 15988001 ER PT J AU Awasthi, S Sharma, A Wong, K Zhang, JY Matlock, EF Rogers, L Motloch, P Takemoto, S Taguchi, H Cole, MD Luescher, B Dittrich, O Tagami, H Nakatani, Y McGee, M Girard, AM Gaughan, L Robson, CN Monnat, RJ Harrod, R AF Awasthi, S Sharma, A Wong, K Zhang, JY Matlock, EF Rogers, L Motloch, P Takemoto, S Taguchi, H Cole, MD Luescher, B Dittrich, O Tagami, H Nakatani, Y McGee, M Girard, AM Gaughan, L Robson, CN Monnat, RJ Harrod, R TI A human T-Cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; CREB BINDING-PROTEIN; TAX-TRANSGENIC MICE; READING FRAME II; LEUKEMIA-VIRUS; C-MYC; HTLV-I; CYCLE PROGRESSION; ESSENTIAL COFACTOR; ONCOGENIC TRANSFORMATION AB The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4(+) lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30(II) markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30(II), is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the stabilization of HTLV-1 p30(II)/Myc-TIP60 chromatin-remodeling complexes. The p30(II), oncoprotein colocalizes and coimmunoprecipitates with Myc-TIP60 complexes in cultured HTLV-1-infected ATLL patient lymphocytes. Amino acid residues 99 to 154 within HTLV-1 p30(II) interact with the TIP60 HAT, and p30(II), transcriptionally activates numerous cellular genes in a TIP60-dependent or TIP60-independent manner, as determined by microarray gene expression analyses. Importantly, these results suggest that p30(II) functions as a novel retroviral modulator of Myc-TIP60-transforming interactions that may contribute to adult T-cell leukemogenesis. C1 So Methodist Univ, Dept Biol Sci, Mol Virol Lab, Dallas, TX 75275 USA. Kochi Med Sch Hosp, Dept Hematol & Resp Med, Nankoku, Kochi 7838505, Japan. Dartmouth Coll, Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. Norris Cotton Canc Ctr, Hanover, NH 03755 USA. Klinikum RWTH, Inst Biochem, Abt Biochem & Mol Biol, D-52057 Aachen, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA. Oregon State Univ, Ctr Gene Res & Biotechnol, Corvallis, OR 97331 USA. Univ Newcastle Upon Tyne, Sch Med, Sch Surg Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Harrod, R (reprint author), So Methodist Univ, Dept Biol Sci, Mol Virol Lab, 334-DLS,6501 Airline Dr, Dallas, TX 75275 USA. EM rharrod@mail.smu.edu OI Takemoto, Shigeki/0000-0003-4130-074X NR 88 TC 42 Z9 44 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 JUL PY 2005 VL 25 IS 14 BP 6178 EP 6198 DI 10.1128/MCB.25.14.6178-6198.2005 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942EZ UT WOS:000230267000032 PM 15988028 ER PT J AU Zou, JH Ichikawa, H Blackburn, ML Hu, HM Zielinska-Kwiatkowska, A Mei, Q Roth, GJ Chansky, HA Yang, L AF Zou, JH Ichikawa, H Blackburn, ML Hu, HM Zielinska-Kwiatkowska, A Mei, Q Roth, GJ Chansky, HA Yang, L TI The oncogenic TLS-ERG fusion protein exerts different effects in hernatopoietic cells and fibroblasts SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ETV6-NTRK3 GENE FUSION; HUMAN MYELOID-LEUKEMIA; RNA-BINDING PROTEIN; EWINGS-SARCOMA; CHROMOSOMAL TRANSLOCATION; DNA; EXPRESSION; EWS/FLI; DOMAIN; TRANSCRIPTION AB The oncogenic TLS-ERG fusion protein is found in human myeloid leukemia and Ewing's sarcoma as a result of specific chromosomal translocation. To unveil the potential mechanism(s) underlying cellular transformation, we have investigated the effects of TLS-ERG on both gene transcription and RNA splicing. Here we show that the TLS protein forms complexes with RNA polymerase II (Pol II) and the serine-arginine family of splicing factors in vivo. Deletion analysis of TLS-ERG in both mouse L-G myeloid progenitor cells and NIH 3T3 fibroblasts revealed that the RNA Pol II-interacting domain of TLS-ERG resides within the first 173 amino acids. While TLS-ERG repressed expression of the luciferase reporter gene driven by glycoprotein IX promoter in L-G cells but not in NIH 3T3 cells, the fusion protein was able to affect splicing of the E1A reporter in NIH 3T3 cells but not in L-G cells. To identify potential target genes of TLS-ERG, the fusion protein and its mutants were stably expressed in both L-G and NIH 3T3 cells through retroviral transduction. Microarray analysis of RNA samples from these cells showed that TLS-ERG activates two different sets of genes sharing little similarity in the two cell lines. Taken together, these results suggest that the oncogenic TLS-ERG fusion protein transforms hematopoietic cells and fibroblasts via different pathways. C1 Univ Washington, Dept Orthoped, Seattle, WA 98195 USA. Univ Washington, Dept Med Hematol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Natl Canc Ctr, Res Inst, Canc Transcriptome Project, Chuo Ku, Tokyo 104, Japan. RP Yang, L (reprint author), Univ Arkansas Med Sci, Dept Pathol, BRCII, Room 641-B2,4301 W Markham St, Little Rock, AR 72205 USA. EM lyang@uams.edu FU NCI NIH HHS [1R01CA090941, R01 CA090941]; NIAMS NIH HHS [1R01AR051455, R01 AR051455] NR 44 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 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 14 BP 6235 EP 6246 DI 10.1128/MCB.25.14.6235-6246.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942EZ UT WOS:000230267000036 PM 15988032 ER PT J AU Chaiswing, L Cole, MP Ittarat, W Szweda, LI St Clair, DK Oberley, TD AF Chaiswing, L Cole, MP Ittarat, W Szweda, LI St Clair, DK Oberley, TD TI Manganese superoxide dismutase and inducible nitric oxide synthase modify early oxidative events in acute Adriamycin-induced mitochondrial toxicity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TRANSGENIC MICE; IN-VIVO; EPITHELIAL-CELLS; PEROXYNITRITE; INJURY; OXYGEN; DAMAGE; CARDIOMYOPATHY; LOCALIZATION; GENERATION AB In the present study, we used genetically engineered B6C3 mice [mice overexpressing manganese superoxide dismutase (TgM(+/+)), mice in which inducible nitric oxide synthase had been inactivated (iNOSKO(-/-)), and crosses of these two genotypes] to study the role of manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS) in the development of acute Adriamycin-induced cardiotoxicity. Both nontransgenic and genetically engineered mice were treated with 20 mg/kg Adriamycin and cardiac left ventricular tissues studied at 0, 3, 6, and 24 hours. Ultrastructural damage and levels of 4-hydroxy-2-nonenal (4HNE) protein adducts and 3-nitrotyrosine (3NT) were determined in cardiomyocytes using immunogold ultrastructural techniques. Our previous results showed that Adriamycin caused mitochondrial injury without significant nuclear or cytoplasmic damage at early time points. Interestingly, overexpression of MnSOD protected against acute mitochondrial injury, whereas deficiency in NOS potentiated mitochondrial injury in comparison with levels of injury present in cardiomyocyte mitochondria of nontransgenic mice. In TgM(+/+) mice, there was a significant inverse correlation between mitochondrial injury and 4HNE/3NT levels at all time points analyzed, suggesting that reactive oxygen species/reactive nitrogen species damage products directly regulated acute Adriamycin-induced mitochondrial injury in these mice. The present studies are the first to directly quantify the effects of MnSOD and NOS on mitochondrial injury during acute Adriamycin-induced cardiotoxicity and show extensive and specific patterns of posttranslational modifications of mitochondrial proteins following Adriamycin treatment. C1 William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI USA. Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand. Univ Kentucky, Dept Toxicol, Lexington, KY USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu FU NCI NIH HHS [CA 49797, CA 80152, CA 94853]; NIDDK NIH HHS [T32DK07778] NR 28 TC 37 Z9 38 U1 0 U2 0 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 JUL PY 2005 VL 4 IS 7 BP 1056 EP 1064 DI 10.1158/1535-7163.MCT-04-0322 PG 9 WC Oncology SC Oncology GA 945XY UT WOS:000230537500004 PM 16020663 ER PT J AU Caruso, ME Jenna, S Beaulne, S Lee, EH Bergeron, A Chauve, C Roby, P Rual, JF Hill, DE Vidal, M Bosse, R Chevet, E AF Caruso, ME Jenna, S Beaulne, S Lee, EH Bergeron, A Chauve, C Roby, P Rual, JF Hill, DE Vidal, M Bosse, R Chevet, E TI Biochemical clustering of monomeric GTPases of the Ras superfamily SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID GTP-BINDING-PROTEIN; CAENORHABDITIS-ELEGANS; EXPRESSION; PURIFICATION; HOMOLOG; CLONING; CELLS; RAC1 AB To date phylogeny has been used to compare entire families of proteins based on their nucleotide or amino acid sequence. Here we developed a novel analytical platform allowing a systematic comparison of protein families based on their biochemical properties. This approach was validated on the Rho subfamily of GTPases. We used two high throughput methods, referred to as AlphaScreen(TM) and FlashPlate(R), to measure nucleotide binding capacity, exchange, and hydrolysis activities of small monomeric GTPases. These two technologies have the characteristics to be very sensitive and to allow homogenous and high throughput assays. To analyze and integrate the data obtained, we developed an algorithm that allows the classification of GTPases according to their enzymatic activities. Integration and hierarchical clustering of these results revealed unexpected features of the small Rho GTPases when compared with primary sequence-based trees. Hence we propose a novel phylobiochemical classification of the Ras superfamily of GTPases. C1 PerkinElmer BioSignal, Montreal, PQ H3J 1R4, Canada. McGill Univ, Dept Surg, Organelle Signaling Lab, Montreal, PQ H3A 2B2, Canada. McGill Univ, Montreal Proteom Network, Montreal, PQ H3A 2B2, Canada. Univ Quebec, Lab Combinatoire & Informat Math, Montreal, PQ H3C 3P8, Canada. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Chevet, E (reprint author), PerkinElmer BioSignal, Montreal, PQ H3J 1R4, Canada. EM eric.chevet@mcgill.ca RI Bergeron, Anne/B-9861-2012; Hill, David/B-6617-2011; Chevet, Eric/E-4992-2016; OI Chevet, Eric/0000-0001-5855-4522; Rual, Jean-Francois/0000-0003-4465-8819 NR 21 TC 14 Z9 21 U1 0 U2 2 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 JUL PY 2005 VL 4 IS 7 BP 936 EP 944 DI 10.1074/mcp.M500025-MCP200 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 943EG UT WOS:000230334500007 PM 15814614 ER PT J AU Abou-Montet, K Montet, X Weissleder, R Josephson, L AF Abou-Montet, Karin Montet, Xavier Weissleder, Ralph Josephson, Lee TI Transfection Agent Induced Nanoparticle Cell Loading SO MOLECULAR IMAGING LA English DT Article DE Transfection agent; nanoparticle; internalization; magnetic resonance; aggregation ID LYMPH-NODE METASTASES; MR CONTRAST AGENTS; IN-VIVO TRACKING; STEM-CELLS; TAT PEPTIDE; FERUMOXIDES; FERUMOXTRAN; PROGENITOR; NECK AB Loading cells with magnetic nanoparticles, and tracking their fate in vivo by high resolution MRI, is an attractive approach for enhancing the efficacy of cell-based therapies including those utilizing hematopoietic stem cells, neuroprogenitor cells, and T cells. The transfection agent (internalization agent) assisted loading with the Feridex IV (R) nanoparticle is an attractive method of loading because of the low cost of materials, and possible low regulatory barriers for eventual clinical use. We therefore explored the interaction between Feridex IV1 and three internalization agents protamine (PRO), polylysine (PLL), and lipofectamine (LFA). Feridex reacted with internalization agents to form aggregates, except when either the internalization agent or Feridex was present in large excess. When Jurkat T cells were incubated with Feridex/LFA or Feridex/PRO mixtures, and washed by centrifugation, nanoparticle aggregates co-purified with cells. With C17.2 cells large iron oxide particles adhered to the cell surface. At 30 mu g/mL Feridex and 3 mu g/mL LFA, internalization was largely mediated by LFA and was largely cytoplasmic. However, we found that the conditions used to label cells with Feridex and transfection agents need to be carefully selected to avoid the problems of surface adsorption and nanoparticle precipitation. Mol Imaging (2005) 4, 165-171. C1 [Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU Swiss National Science Foundation [PPOB-68778]; Geneva University Hospital; [R01-EB00662-A01]; [R01 EB004626] FX K. M. A. was supported by the Swiss National Science Foundation (grant PPOB-68778) and X. M. was supported by fellowships from the Geneva University Hospital.; We thank Dr. Evan Snyder for supplying C17.2 cells. This research was funded in part by R01-EB00662-A01 and R01 EB004626. NR 19 TC 12 Z9 13 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD JUL PY 2005 VL 4 IS 3 BP 165 EP 171 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V22HD UT WOS:000208265400002 ER PT J AU Crosby, MB Svenson, J Gilkeson, GS Nowling, TK AF Crosby, MB Svenson, J Gilkeson, GS Nowling, TK TI A novel PPAR response element in the murine iNOS promoter SO MOLECULAR IMMUNOLOGY LA English DT Article DE PPAR gamma; iNOS; TZD; gene regulation ID ACTIVATED RECEPTOR-GAMMA; NITRIC-OXIDE SYNTHASE; MRL-LPR/LPR MICE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY CYTOKINES; AUTOIMMUNE-DISEASE; BINDING PROTEIN; IFN-GAMMA; AGONISTS; GENE AB The nuclear hormone receptor peroxisome proliferation activated receptor gamma (PPAR gamma) is a modulator of inflammation including down-regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production. PPAR gamma agonists reduce iNOS expression and NO production in a dose-dependent manner in macrophages, mesangial cells and other inflammatory cells. However, the mechanisms involved in the inhibition of iNOS expression by PPAR gamma and its agonists are not fully understood. Here we show that the PPAR gamma agonist ciglitazone dose-dependently inhibited a murine iNOS-luciferase reporter construct by up to 50% in transfected mesangial cells. Blocking de novo protein synthesis in mesangial cells had no effect on PPAR gamma agonist activity, indicating that ciglitazone acts directly to inhibit iNOS transcription. We identified a novel PPAR response element (PPRE) in the murine iNOS promoter that is homologous to the PPRE consensus sequence. In binding assays PPAR gamma directly binds to this response element in vitro and can function as a positive element in response to PPAR gamma agonists when placed in front of a reporter gene. Site-directed mutagenesis of this PPRE in a murine iNOS promoter/reporter construct did not block the inhibitory activity of a synthetic PPAR gamma agonist on the iNOS promoter/reporter construct in transfected mesangial cells. However, the mutated construct exhibited lower basal expression, and higher expression in response to inflammatory stimuli compared to the intact construct. These data suggest that the iNOS PPRE contributes to positive basal expression and negative expression of iNOS in response to inflammatory stimuli. The PPRE is not necessary, however, for synthetic PPAR gamma agonists to inhibit iNOS expression. (c) 2005 Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Med Res Serv, Charleston, SC 29425 USA. RP Nowling, TK (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathon Lucas St,Ste 912 CSB, Charleston, SC 29425 USA. EM nowling@musc.edu FU NIAMS NIH HHS [AR47451]; NIGMS NIH HHS [GM08716] NR 29 TC 31 Z9 34 U1 0 U2 3 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 JUL PY 2005 VL 42 IS 11 BP 1303 EP 1310 DI 10.1016/j.molimm.2004.12.009 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 943EX UT WOS:000230336400005 PM 15950726 ER PT J AU Jain, RK Au, P Tam, J Duda, DG Fukumura, D AF Jain, RK Au, P Tam, J Duda, DG Fukumura, D TI Engineering vascularized tissue SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID IN-VIVO; CELLS; VESSEL C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 14 TC 276 Z9 290 U1 5 U2 49 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 821 EP 823 DI 10.1038/nbt0705-821 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700025 PM 16003365 ER PT J AU Daley, GQ AF Daley, GQ TI Customized human embryonic stem cells SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID NUCLEAR TRANSPLANTATION; THERAPY; MICE; GENE C1 Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 826 EP 828 DI 10.1038/nbt0705-826 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700028 PM 16003368 ER PT J AU Han, JDJ Dupuy, D Bertin, N Cusick, ME Vidal, M AF Han, JDJ Dupuy, D Bertin, N Cusick, ME Vidal, M TI Effect of sampling on topology predictions of protein-protein interaction networks SO NATURE BIOTECHNOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; COMPLEX NETWORKS; SCALE-FREE; YEAST; MODULES; ORGANIZATION; STRATEGY; ELEGANS; BIOLOGY AB Currently available protein-protein interaction (PPI) network or 'interactome' maps, obtained with the yeast two-hybrid (Y2H) assay or by co-affinity purification followed by mass spectrometry (co-AP/MS), only cover a fraction of the complete PPI networks. These partial networks display scale-free topologies-most proteins participate in only a few interactions whereas a few proteins have many interaction partners. Here we analyze whether the scale-free topologies of the partial networks obtained from Y2H assays can be used to accurately infer the topology of complete interactomes. We generated four theoretical interaction networks of different topologies ( random, exponential, power law, truncated normal). Partial sampling of these networks resulted in sub-networks with topological characteristics that were virtually indistinguishable from those of currently available Y2H-derived partial interactome maps. We conclude that given the current limited coverage levels, the observed scale-free topology of existing interactome maps cannot be confidently extrapolated to complete interactomes. C1 Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Dupuy, Denis/M-7299-2014; OI Bertin, Nicolas/0000-0002-9835-9606; Dupuy, Denis/0000-0002-4781-5595 NR 51 TC 207 Z9 218 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 839 EP 844 DI 10.1038/nbt1116 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700031 PM 16003372 ER PT J AU Bonner-Weir, S Weir, GC AF Bonner-Weir, S Weir, GC TI New sources of pancreatic beta-cells SO NATURE BIOTECHNOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; INSULIN-PRODUCING CELLS; TYPE-1 DIABETES-MELLITUS; EPIDERMAL-GROWTH-FACTOR; WORK-IN-PROGRESS; BONE-MARROW; EXPRESSING CELLS; PROGENITOR CELLS; NOD MICE; ISLET TRANSPLANTATION AB Two major initiatives are under way to correct the beta-cell deficit of diabetes: one would generate beta-cells ex vivo that are suitable for transplantation, and the second would stimulate regeneration of beta-cells in the pancreas. Studies of ex vivo expansion suggest that cells have a potential for dedifferentiation, expansion, and redifferentiation. Work with mouse and human embryonic stem (ES) cells has not yet produced cells with the phenotype of true beta-cells, but there has been recent progress in directing ES cells to endoderm. Putative islet stem/progenitor cells have been identified in mouse pancreas, and formation of new-cells from duct, acinar and liver cells is an active area of investigation. Peptides, including glucagon-like peptide-1/exendin-4 and the combination of epidermal growth factor and gastrin, can stimulate regeneration of beta-cells in vivo. Recent progress in the search for new sources of beta-cells has opened promising new opportunities and spawned clinical trials. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 77 TC 275 Z9 292 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 857 EP 861 DI 10.1038/nbt1115 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700033 PM 16003374 ER PT J AU Levenberg, S Rouwkema, J Macdonald, M Garfein, ES Kohane, DS Darland, DC Marini, R van Blitterswijk, CA Mulligan, RC D'Amore, PA Langer, R AF Levenberg, S Rouwkema, J Macdonald, M Garfein, ES Kohane, DS Darland, DC Marini, R van Blitterswijk, CA Mulligan, RC D'Amore, PA Langer, R TI Engineering vascularized skeletal muscle tissue SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; ENDOTHELIAL SURVIVAL; DIFFERENTIATION; ANGIOGENESIS; MECHANISMS; DELIVERY; MATRICES AB One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation. C1 Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Twente, Inst Biomed Technol, NL-3723 MB Bilthoven, Netherlands. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Mol Med, Childrens Hosp, Boston, MA 02115 USA. RP Langer, R (reprint author), Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. EM shulamit@bm.technion.ac.il; rlanger@mit.edu OI Rouwkema, Jeroen/0000-0001-9666-9064; van Blitterswijk, Clemens/0000-0003-2371-4615 FU NEI NIH HHS [EY05318]; NHLBI NIH HHS [HL60435] NR 26 TC 634 Z9 655 U1 14 U2 181 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 879 EP 884 DI 10.1038/nbt1109 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700036 PM 15965465 ER PT J AU Degterev, A Huang, ZH Boyce, M Li, YQ Jagtap, P Mizushima, N Cuny, GD Mitchison, TJ Moskowitz, MA Yuan, JY AF Degterev, A Huang, ZH Boyce, M Li, YQ Jagtap, P Mizushima, N Cuny, GD Mitchison, TJ Moskowitz, MA Yuan, JY TI Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury SO NATURE CHEMICAL BIOLOGY LA English DT Article ID RECEPTOR-INTERACTING PROTEIN; NECROSIS-FACTOR-ALPHA; POLY(ADP-RIBOSE) POLYMERASE; FAS RECEPTOR; IN-VITRO; APOPTOSIS; AUTOPHAGY; PATHWAY; STROKE; MECHANISMS AB The mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. Although stimulation of the Fas/TNFR receptor family triggers a canonical 'extrinsic' apoptosis pathway, we demonstrated that in the absence of intracellular apoptotic signaling it is capable of activating a common nonapoptotic death pathway, which we term necroptosis. We showed that necroptosis is characterized by necrotic cell death morphology and activation of autophagy. We identified a specific and potent small- molecule inhibitor of necroptosis, necrostatin-1, which blocks a critical step in necroptosis. We demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection. Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. Harvard Univ, Ctr Neurodegenerat & Repair, Lab Drug Discovery Neurodegenerat, Brigham & Womens Hosp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02139 USA. Tokyo Metropolitan Inst Med Sci, Dept Bioregulat & Metab, Tokyo 1138613, Japan. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM jyuan@hms.harvard.edu RI Mizushima, Noboru/C-3635-2009 OI Mizushima, Noboru/0000-0002-6258-6444 FU NIA NIH HHS [R37 AG012859]; NIGMS NIH HHS [R01 GM64703]; NINDS NIH HHS [R01 NS37141-08] NR 37 TC 905 Z9 985 U1 11 U2 116 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JUL PY 2005 VL 1 IS 2 BP 112 EP 119 DI 10.1038/nchembio711 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 975GE UT WOS:000232648200016 PM 16408008 ER PT J AU Grant, PE AF Grant, PE TI Can noninvasive imaging of biomarkers improve clinical grading of pediatric brain tumors? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE choline; lactate; lipid; magnetic resonance spectroscopy; pediatric brain tumor ID SPECTROSCOPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Ellison 237,55 Fruit St, Boston, MA 02114 USA. EM pegrant@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2005 VL 2 IS 7 BP 336 EP 337 DI 10.1038/ncponc0203 PG 2 WC Oncology SC Oncology GA 962QE UT WOS:000231746500004 PM 16075788 ER PT J AU Reiser, J Polu, KR Moller, CC Kenlan, P Altintas, MM Wei, CL Faul, C Herbert, S Villegas, I Avila-Casado, C McGee, M Sugimoto, H Brown, D Kalluri, R Mundel, P Smith, PL Clapham, DE Pollak, MR AF Reiser, J Polu, KR Moller, CC Kenlan, P Altintas, MM Wei, CL Faul, C Herbert, S Villegas, I Avila-Casado, C McGee, M Sugimoto, H Brown, D Kalluri, R Mundel, P Smith, PL Clapham, DE Pollak, MR TI TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function SO NATURE GENETICS LA English DT Article ID NEPHROTIC-SYNDROME; NEPHRIN; PROTEIN; KIDNEY; PODOCYTES; RAT; GENE AB Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 ( TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Inst Nacl Cardiol Ignacio Chavez, Dept Pathol, Mexico City 14080, DF, Mexico. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA. RP Reiser, J (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02129 USA. EM jreiser@partners.org; mpollak@rics.bwh.harvard.edu RI Faul, Christian/D-1549-2011; Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Altintas, Mehmet/0000-0002-1871-6985 FU NIDDK NIH HHS [R01 DK054931, R01 DK055001, R01 DK057683, R56 DK054931] NR 26 TC 410 Z9 450 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2005 VL 37 IS 7 BP 739 EP 744 DI 10.1038/ng1592 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 941EA UT WOS:000230196400021 PM 15924139 ER PT J AU Wang, YX Putnam, CD Kane, MF Zhang, WJ Edelmann, L Russell, R Carrion, DV Chin, L Kucherlapati, R Kolodner, RD Edelmann, W AF Wang, YX Putnam, CD Kane, MF Zhang, WJ Edelmann, L Russell, R Carrion, DV Chin, L Kucherlapati, R Kolodner, RD Edelmann, W TI Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal instability and cancer in mice SO NATURE GENETICS LA English DT Article ID REPLICATION PROTEIN-A; SACCHAROMYCES-CEREVISIAE; GENOME INSTABILITY; CHECKPOINT FUNCTIONS; SHORT ARM; RECOMBINATION; REARRANGEMENTS; DAMAGE; SUPPRESSION; YEAST AB Most cancers have multiple chromosomal rearrangements; the molecular mechanisms that generate them remain largely unknown. Mice carrying a heterozygous missense change in one of the DNA- binding domains of Rpa1 develop lymphoid tumors, and their homozygous littermates succumb to early embryonic lethality. Array comparative genomic hybridization of the tumors identified large- scale chromosomal changes as well as segmental gains and losses. The Rpa1 mutation resulted in defects in DNA double- strand break repair and precipitated chromosomal breaks as well as aneuploidy in primary heterozygous mutant mouse embryonic fibroblasts. The equivalent mutation in yeast is hypomorphic and semidominant and enhanced the formation of gross chromosomal rearrangements in multiple genetic backgrounds. These results indicate that Rpa1 functions in DNA metabolism are essential for the maintenance of chromosomal stability and tumor suppression. C1 Univ Calif San Diego, Ludwig Inst Canc Res, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Ctr Genet & Genom, Harvard Med Sch Partners Healthcare Ctr Genet & G, Boston, MA 02115 USA. NYU, Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, Ctr Canc, La Jolla, CA 92093 USA. EM rkolodner@ucsd.edu; edelmann@aecom.yu.edu NR 30 TC 81 Z9 81 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2005 VL 37 IS 7 BP 750 EP 755 DI 10.1038/ng1587 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 941EA UT WOS:000230196400023 PM 15965476 ER PT J AU von Boehmer, H AF von Boehmer, H TI Notch in lymphopoiesis and T cell polarization SO NATURE IMMUNOLOGY LA English DT Editorial Material ID LYMPHOID PROGENITORS; IN-VITRO; LINEAGES; CD4 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 17 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2005 VL 6 IS 7 BP 641 EP 642 DI 10.1038/ni0705-641 PG 2 WC Immunology SC Immunology GA 938BS UT WOS:000229975500003 PM 15970933 ER PT J AU Heissmeyer, V Ansel, KM Rao, AJ AF Heissmeyer, V Ansel, KM Rao, AJ TI A plague of autoantibodies SO NATURE IMMUNOLOGY LA English DT Editorial Material ID HELPER-CELLS; T-CELLS; AUTOIMMUNITY C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Heissmeyer, V (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2005 VL 6 IS 7 BP 642 EP 644 DI 10.1038/ni1214 PG 4 WC Immunology SC Immunology GA 938BS UT WOS:000229975500004 PM 15991362 ER PT J AU Laouar, A Haridas, V Vargas, D Xia, ZN Chaplin, D van Lier, RAW Manjunath, N AF Laouar, A Haridas, V Vargas, D Xia, ZN Chaplin, D van Lier, RAW Manjunath, N TI CD70(+) antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa SO NATURE IMMUNOLOGY LA English DT Article ID SYSTEMIC VIRUS-INFECTION; ALPHA-DEFICIENT MICE; INTRAEPITHELIAL LYMPHOCYTES; DENDRITIC CELLS; LISTERIA-MONOCYTOGENES; LAMINA PROPRIA; TOLERANCE INDUCTION; TRANSGENIC MICE; PEYERS PATCH; IFN-GAMMA AB One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had antigen-presenting functions. After oral infection of mice with Listeria monocytogenes, proliferation and differentiation of antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. Acad Med Ctr, Expt Immunol Lab, NL-1105 AZ Amsterdam, Netherlands. RP Manjunath, N (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM swamy@cbr.med.harvard.edu OI van Lier, Rene/0000-0002-3201-7144; Chaplin, David/0000-0002-1354-3069 FU NIAID NIH HHS [AI46566, R01 AI046566, R21 AI046566] NR 57 TC 76 Z9 78 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2005 VL 6 IS 7 BP 698 EP 706 DI 10.1038/ni1212 PG 9 WC Immunology SC Immunology GA 938BS UT WOS:000229975500013 PM 15937486 ER PT J AU Huang, ZL Qu, WM Eguchi, N Chen, JF Schwarzschild, MA Fredholm, BB Urade, Y Hayaishi, O AF Huang, ZL Qu, WM Eguchi, N Chen, JF Schwarzschild, MA Fredholm, BB Urade, Y Hayaishi, O TI Adenosine A2(A), but not A(1), receptors mediate the arousal effect of caffeine SO NATURE NEUROSCIENCE LA English DT Article ID HOMEOSTATIC REGULATION; SLEEP; RATS AB Caffeine, a component of tea, coffee and cola, induces wakefulness. It binds to adenosine A(1) and A(2A) receptors as an antagonist, but the receptor subtype mediating caffeine-induced wakefulness remains unclear. Here we report that caffeine at 5, 10 and 15 mg kg(-1) increased wakefulness in both wild-type mice and A(1) receptor knockout mice, but not in A(2A) receptor knockout mice. Thus, caffeine-induced wakefulness depends on adenosine A(2A) receptors. C1 Osaka Biosci Inst, Dept Mol Behav Biol, Osaka 5650874, Japan. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02129 USA. Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. RP Hayaishi, O (reprint author), Osaka Biosci Inst, Dept Mol Behav Biol, Osaka 5650874, Japan. EM hayaishi@obi.or.jp NR 15 TC 233 Z9 250 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2005 VL 8 IS 7 BP 858 EP 859 DI 10.1038/nn1491 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 940IK UT WOS:000230137100010 PM 15965471 ER PT J AU von Boehmer, H AF von Boehmer, H TI Opinion - Unique features of the pre-T-cell receptor alpha-chain: not just a surrogate SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID GAMMA-DELTA; ALLELIC EXCLUSION; PT-ALPHA; LYMPHOCYTE DEVELOPMENT; TRANSGENIC MICE; BETA LOCUS; TCR-BETA; THYMOCYTE DEVELOPMENT; SURFACE EXPRESSION; DEFICIENT MICE AB The pre-T-cell receptor (pre-TCR) has a crucial role in the normal development of a T cells. Different views have emerged concerning the structure and function of the pre-TCR. This molecular complex can be viewed as a variant of the alpha beta -TCR in which the pre-TCR alpha-chain that is covalently associated with the TCR beta-chain is a 'surrogate' TCR alpha-chain. Alternatively, the unique structure of the pre-TCR might be associated with a unique function, owing to evolutionary selection of a pre-TCR alpha-chain that has different capabilities from the TCR alpha-chain. As described here, I consider that experimental evidence favours the latter view. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Harald_Von_Boehmer@dfci.harvard.edu NR 79 TC 83 Z9 85 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUL PY 2005 VL 5 IS 7 BP 571 EP 577 DI 10.1038/nri1636 PG 7 WC Immunology SC Immunology GA 944KL UT WOS:000230426700015 PM 15999096 ER PT J AU Czanner, G Grun, S Iyengar, S AF Czanner, G Grun, S Iyengar, S TI Theory of the snowflake plot and its relations to higher-order analysis methods SO NEURAL COMPUTATION LA English DT Article ID SPATIOTEMPORAL FIRING PATTERNS; NEURONS; ENSEMBLES; DISPLAY; CORTEX; MEMORY; TRAINS AB The snowflake plot is a scatter plot that displays relative timings of three neurons. It has had rather limited use since its introduction by Perkel, Gerstein, Smith, and Tatton (1975), in part because its triangular coordinates are unfamiliar and its theoretical properties are not well studied. In this letter, we study certain quantitative properties of this plot: we use projections to relate the snowflake plot to the cross-correlation histogram and the spike-triggered joint histogram, study the sampling properties of the plot for the null case of independent spike trains, study a simulation of a coincidence detector, and describe the extension of this plot to more than three neurons. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Free Univ Berlin, Inst Biol Neurobiol, D-14195 Berlin, Germany. RP Czanner, G (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM gabriela@neurostat.mgh.harvard.edu; gruen@neurobiologie.fu-berlin.de; si@stat.pitt.edu OI Grun, Sonja/0000-0003-2829-2220 NR 26 TC 14 Z9 14 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD JUL PY 2005 VL 17 IS 7 BP 1456 EP 1479 DI 10.1162/0899766053723041 PG 24 WC Computer Science, Artificial Intelligence SC Computer Science GA 924LK UT WOS:000228980100002 PM 15901404 ER PT J AU Barker, F Curry, W Carter, B AF Barker, F Curry, W Carter, B TI Racial disparities in patient outcome after craniotomy for tumors in the United States, 1988-2000 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 85 BP 303 EP 303 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900090 ER PT J AU Raizer, J Abrey, L Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M AF Raizer, J Abrey, L Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M TI A phase I trial of OSI-774 (tarceva) in patients (pts) with recurrent malignant gliomas (MG) on enzyme inducing anti-convulsants: A North American Brain Tumor Consortium Trial SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. NCI, NIH, Neuro Oncol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 154 BP 320 EP 321 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900158 ER PT J AU Manley, P Turner, C Chi, S Zimmerman, M Chordas, C Gordon, A Thomas, A Hoffman, K Kieran, M AF Manley, P Turner, C Chi, S Zimmerman, M Chordas, C Gordon, A Thomas, A Hoffman, K Kieran, M TI A prospective, blinded analysis of A-PROTEIN levels in pediatric patients with central nervous system tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Cytra Corp, Wrentham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 202 BP 332 EP 332 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900206 ER PT J AU Kolak, GC Henson, JW Leahy, NM Stephen, E Pappas, C AF Kolak, GC Henson, JW Leahy, NM Stephen, E Pappas, C TI The impact of the nurse practitioner on length of stay of neuro-oncology patients in an acute care setting in a large teaching hospital SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Neuro Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 212 BP 335 EP 335 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900216 ER PT J AU Finlay, J Allen, J Diez, B Kellie, S Chi, S Asgharzadeh, S Zacharoulis, S Gardner, S AF Finlay, J Allen, J Diez, B Kellie, S Chi, S Asgharzadeh, S Zacharoulis, S Gardner, S TI Outcome of intensive induction chemotherapy followed by consolidative myeloablative chemotherapy and autologous stem cell rescue (AuSCR) in young children with newly diagnosed non-cerebellar primitive neuroectodermal tumors (PNET): The "Head Start" I and II protocols SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Childrens Hosp Los Angeles, Neural Tumors Program, Los Angeles, CA 90027 USA. NYU, New York, NY USA. Inst FLENI, Buenos Aires, DF, Argentina. Childrens Hosp Westmead, Westmead, NSW, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 269 BP 351 EP 351 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900269 ER PT J AU Brennan, C Feng, B Louis, D Black, PM Chin, L AF Brennan, C Feng, B Louis, D Black, PM Chin, L TI Amplifications and deletions in the glioblastoma genome: From novel loci to candidate gene and non-gene targets SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. OI Brennan, Cameron/0000-0003-4064-8891 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 311 BP 361 EP 361 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900311 ER PT J AU Jeyapalan, S Pasternack, M Knipe, D Hochberg, FH Reilly, K AF Jeyapalan, S Pasternack, M Knipe, D Hochberg, FH Reilly, K TI Immune rejection of gliomas in a murine model SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 354 BP 372 EP 372 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900354 ER PT J AU Previti, M Chamberlain, M Kesari, S Wen, P Edwards, K Van Horn, A Glantz, M AF Previti, M Chamberlain, M Kesari, S Wen, P Edwards, K Van Horn, A Glantz, M TI Levetiracetam (LEV) monotherapy in patients with primary brain tumors (PBTs): Efficacy, side effects, and CSF and plasma pharmacokinetics SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Univ So Calif, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 372 BP 376 EP 376 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900372 ER PT J AU Lamfers, M Gianni, D Tung, CH Idema, S Quax, PH van Beusechem, VW Vandertop, WP Dirven, CMF Chiocca, EA Gerritsen, WR AF Lamfers, M Gianni, D Tung, CH Idema, S Quax, PH van Beusechem, VW Vandertop, WP Dirven, CMF Chiocca, EA Gerritsen, WR TI Tissue inhibitor of metalloproteinases-3 expression in the context of an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo but does not enhance antitumor efficacy in malignant glioma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 VU Univ Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neuro Oncol Labs,Neurol Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. TNO PG, Gaubius Lab, Leiden, Netherlands. VU Univ Med Ctr, Dept Med Oncol, Div Gene Therapy, Amsterdam, Netherlands. RI Gerritsen, W.R./H-8031-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 384 BP 379 EP 380 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900384 ER PT J AU Sathornsumetee, S Batt, D Kieran, M Kier, S Ramsey, T Yusuff, N Reardon, D Bigner, D Friedman, H Rich, J AF Sathornsumetee, S Batt, D Kieran, M Kier, S Ramsey, T Yusuff, N Reardon, D Bigner, D Friedman, H Rich, J TI Targeting malignant gliomas with a low-molecular-weight Raf/vascular endothelial growth factor receptor inhibitor SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Novartis Inst Biomed Res, Dept Oncol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 381 BP 379 EP 379 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900381 ER PT J AU Mrugala, MM Schreiber, S Knobbe, CB Muzikansky, A Harris, GJ Rabinov, J Hochberg, FH AF Mrugala, MM Schreiber, S Knobbe, CB Muzikansky, A Harris, GJ Rabinov, J Hochberg, FH TI Primary central nervous system lymphoma - Volumetric analysis of response to chemotherapy: Is there predictive value to a "response nomogram"? SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 450 BP 396 EP 396 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900449 ER PT J AU Auranen, T Nummenmaa, A Hamalainen, MS Jaaskelainen, IP Lampinen, J Vehtari, A Sams, M AF Auranen, T Nummenmaa, A Hamalainen, MS Jaaskelainen, IP Lampinen, J Vehtari, A Sams, M TI Bayesian analysis of the neuromagnetic inverse problem with l(p)-norm priors SO NEUROIMAGE LA English DT Article DE MEG inverse; Bayesian inference; l(p)-norm; MCMC; slice sampling ID CORTICAL ACTIVITY; MEG DATA; EEG; LOCALIZATION; FMRI; RECONSTRUCTION; SIGNAL; MODEL; MRI AB Magnetoencephalography (MEG) allows millisecond-scale non-invasive measurement of magnetic fields generated by neural currents in the brain. However, localization of the underlying current sources is ambiguous due to the so-called inverse problem. The most widely used source localization methods (i.e., minimum-norm and minimum-current estimates (NINE and MCE) and equivalent current dipole (ECD) fitting) require ad hoc determination of the cortical current distribution (l(2)-, l(1)-norm priors and point-sized dipolar, respectively). In this article, we perform a Bayesian analysis of the MEG inverse problem with l(p)-norm priors for the current sources. This way, we circumvent the arbitrary choice between l(1)- and l(2)-norm prior, which is instead rendered automatically based on the data. By obtaining numerical samples from the joint posterior probability distribution of the source current parameters and model hyperparameters (such as the l(p)-norm order p) using Markov chain Monte Carlo (MCMC) methods, we calculated the spatial inverse estimates as expectation values of the source current parameters integrated over the hyperparameters. Real MEG data and simulated (known) source currents with realistic MRI-based cortical geometry and 306-channel MEG sensor array were used. While the proposed model is sensitive to source space discretization size and computationally rather heavy, it is mathematically straightforward, thus allowing incorporation of, for instance, a priori functional magnetic resonance imaging (fMRI) information. (c) 2005 Elsevier Inc. All rights reserved. C1 Helsinki Univ Technol, Lab Computat Engn, Espoo 02015, Finland. Helsinki Univ Technol, Adv Magnet Imaging Ctr, Espoo, Finland. Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Charlestown, MA 02139 USA. Helsinki Univ Technol, Low Temp Lab, Brain Res Unit, FIN-02150 Espoo, Finland. RP Auranen, T (reprint author), Helsinki Univ Technol, Lab Computat Engn, POB 9203, Espoo 02015, Finland. EM Toni.Auranen@hut.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Vehtari, Aki/A-7584-2008; Hamalainen, Matti/C-8507-2013; Lampinen, Jouko/D-3927-2014; Auranen, Toni/J-7137-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Vehtari, Aki/0000-0003-2164-9469; FU NICHD NIH HHS [R01-HD40712] NR 40 TC 34 Z9 34 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2005 VL 26 IS 3 BP 870 EP 884 DI 10.1016/j.neuroimage.2005.02.046 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 941JM UT WOS:000230211100023 PM 15955497 ER PT J AU Goldstein, JM Jerram, M Poldrack, R Anagnoson, R Breiter, HC Makris, N Goodman, JM Tsuang, MT Seidman, LJ AF Goldstein, JM Jerram, M Poldrack, R Anagnoson, R Breiter, HC Makris, N Goodman, JM Tsuang, MT Seidman, LJ TI Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory SO NEUROPSYCHOLOGY LA English DT Article DE sex differences; working memory; attention; fMRI ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; ADULT HUMAN BRAIN; GENDER-DIFFERENCES; FUNCTIONAL-ORGANIZATION; GONADAL-HORMONES; TASK-DIFFICULTY; FRONTAL-CORTEX; RHESUS-MONKEY AB Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results. C1 Harvard Univ,Med Sch, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth,Dept Psychiat, Boston, MA 02120 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Jamaica Plain, MA USA. Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ,Med Sch, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth,Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Cambridge, MA 02138 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Ctr Morphometr Anal, Dept Neurol, Med Sch,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Ctr Morphometr Anal, Dept Neurol, Med Sch,Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Goldstein, JM (reprint author), Harvard Univ,Med Sch, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth,Dept Psychiat, 1 Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU NIMH NIH HHS [R03 MH55748] NR 84 TC 79 Z9 81 U1 10 U2 25 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JUL PY 2005 VL 19 IS 4 BP 509 EP 519 DI 10.1037/0894-4105.19.4.509 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 951BC UT WOS:000230902800012 PM 16060826 ER PT J AU Curry, WT Butler, WE Barker, FG AF Curry, WT Butler, WE Barker, FG TI Rapidly rising incidence of cerebrospinal fluid shunting procedures for idiopathic intracranial hypertension in the United States, 1988-2002 SO NEUROSURGERY LA English DT Article DE cerebrospinal fluid shunting; indiopathic intracranial hypertension; incidence ID NERVE SHEATH DECOMPRESSION; PREVENTION CONFERENCE VII; PEDIATRIC PSEUDOTUMOR CEREBRI; INDUCED WEIGHT-LOSS; BARIATRIC SURGERY; DESCRIPTIVE EPIDEMIOLOGY; MORBID-OBESITY; HEART-DISEASE; LUMBOPERITONEAL SHUNT; DIVERSION PROCEDURES AB OBJECTIVE: Obesity, a major risk factor for idiopathic intracranial hypertension (IIH), is rapidly increasing in all ages of the United States population. We studied trends in the incidence of cerebrospinal fluid (CSF) shunts for IIH in the United States between 1988 and 2002, using a national hospital discharge database. METHODS: This was a retrospective study using the Nationwide Inpatient Sample and robust weighted least-squares regression, adjusted for stratified survey methodology. RESULTS: There were 2779 admissions for CSF shunting procedures (new or revision) in IIH patients in the database. In-hospital mortality for new shunts was 0.5% (0.9% for ventricular shunts and 0.2% for lumbar shunts). The estimated total United States caseload of CSF shunting procedures for IIH increased 350% between 1988 and 2002 (P < 0.001). (The 2002 United States caseload was 1370 admissions.) New shunt placements increased 320% during this interval (P < 0.001). In some subpopulations in which obesity is less important as a risk factor for IIH, caseload increases were less marked: pediatric IIH shunting (age < 13 yr) increased 52% and shunting in male IIH patients increased 38%, but shunting in older patients (age > 44 yr) increased 240% during the study period. Bariatric procedures (e.g., gastric bypass) increased very rapidly in incidence since 1998, with nearly 200 such procedures performed on IIH patients in 2002. CONCLUSION: The incidence of CSF shunting for IIH is increasing in the population of the United States at about the same relative rate as morbid obesity. Studies to establish the best shunting method in IIH and to explore alternative treatment strategies, such as optic nerve sheath fenestration and bariatric surgery, are urgently needed. C1 Massachusetts Gen Hosp, Pappas Ctr NeuroOncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Neurosurg Serv, Ctr Neurooncol, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Pappas Ctr NeuroOncol, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 83 TC 56 Z9 57 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2005 VL 57 IS 1 BP 97 EP 107 DI 10.1227/01.NEU.0000163094.23923.E5 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 942ZQ UT WOS:000230321800030 PM 15987545 ER PT J AU Hoh, BL Ogilvy, CS AF Hoh, BL Ogilvy, CS TI Endovascular treatment of cerebral vasospasm: Transluminal balloon angioplasty, intra-arterial papaverine, and intra-arterial nicardipine SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; SYMPTOMATIC VASOSPASM; COOPERATIVE ANEURYSM; BLOOD-FLOW; INTRAVENOUS NICARDIPINE; MORPHOLOGICAL-CHANGES; RANDOMIZED-TRIAL; INFUSION; THERAPY; EXPERIENCE AB Cerebral vasospasm is still one of the leading causes of morbidity and mortality from subarachnoid hemorrhage. Vasospasm refractory to medical management can be treated with enclovascular therapies, such as transluminal balloon angioplasty or infusion of intra-arterial vasodilating agents. In our review of clinical series reported in the English language literature, transluminal balloon angioplasty produced clinical improvement in 62% of patients, significantly improved mean transcranial Doppler (TCD) velocities (P < .05), significantly improved cerebral blood flow (CBF) in 85% of patients as studied by 133 Xenon techniques and serial single photon emission computerized tomography, and was associated with 5.0% complications and 1.1% vessel rupture. Intra-arterial papaverine therapy produced clinical improvement in 43% of patients but only transiently, requiring multiple treatment sessions (1.7 treatments per patient); significantly improved mean TCD velocities (P < .01) but only for less than 48 hours; improved CBF in 60% of patients but only for less than 12 hours; and was associated with increases in intracranial pressure and 9.9% complications. Intra-arterial nicardipine therapy produced clinical improvement in 42% of patients, significantly improved mean TCD velocities (P < .001) for 4 days, and was associated with no complications in our small series. We have adopted a treatment protocol at our institution of transluminal balloon angioplasty and intra-arterial nicardipine therapy as the endovascular treatments for medically refractory cerebral vasospasm. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Hoh, BL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, VBK 710,55 Fruit St, Boston, MA 02114 USA. EM bhoh@partners.org NR 70 TC 51 Z9 52 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 2005 VL 16 IS 3 BP 501 EP + DI 10.1016/j.nec.2005.04.004 PG 17 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 949ZN UT WOS:000230827500005 PM 15990041 ER PT J AU Sisterson, JM Ullmann, J AF Sisterson, JM Ullmann, J TI Measurements of energy integrated cross sections for reactions producing relatively short-lived radionuclides using neutron beams with an energy range of 0.1-750 MeV SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE cosmic rays; spallation reactions; 'white' neutron beams; energy integrated cross section measurements ID COSMIC-RAY PARTICLES; COSMOGENIC NUCLIDES; PRODUCTION-RATES; NOBLE-GASES; DEPENDENCE; CHONDRITE; DETECTOR; CAPTURE AB Energy integrated cross sections for neutron-induced reactions producing relatively short lived radionuclides were measured using 'white' neutron beams with an energy range of 0.1-750 MeV at the Los Alamos Neutron Science Center (LANSCE). Cross sections for neutron-induced reactions are needed as input to the theoretical models used to understand the production of the radionuclide and stable isotopes produced by cosmic ray interactions with extraterrestrial bodies. Although most primary cosmic rays are protons, significant quantities of short- and long-lived radionuclides and stable isotopes are produced by spallation reactions initiated by secondary neutrons produced in primary cosmic ray interactions. Materials irradiated contained the elements commonly found in lunar rocks and meteorites, including SiO2 (for O), Si, CaCO3 (for Ca), Al, Mg, Fe, Ni and KNO3 (for K). Published by Elsevier B.V. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Los Alamos Natl Lab, LANSCE, Los Alamos, NM 87545 USA. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jsisterson@partners.org NR 36 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD JUL PY 2005 VL 234 IS 4 BP 419 EP 430 DI 10.1016/j.nimb.2005.02.023 PG 12 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 942DA UT WOS:000230261900004 ER PT J AU Chen, T Abbey, K Deng, WJ Cheng, MC AF Chen, T Abbey, K Deng, WJ Cheng, MC TI The bioinformatics resource for oral pathogens SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STANFORD MICROARRAY DATABASE; GENE ONTOLOGY; SWISS-PROT; IMPLEMENTATION; INTERPRO; TREMBL; MIAME AB Complete genomic sequences of several oral pathogens have been deciphered and multiple sources of independently annotated data are available for the same genomes. Different gene identification schemes and functional annotation methods used in these databases present a challenge for cross-referencing and the efficient use of the data. The Bioinformatics Resource for Oral Pathogens (BROP) aims to integrate bioinformatics data from multiple sources for easy comparison, analysis and data-mining through specially designed software interfaces. Currently, databases and tools provided by BROP include: (i) a graphical genome viewer (Genome Viewer) that allows side-by-side visual comparison of independently annotated datasets for the same genome; (ii) a pipeline of automatic data-mining algorithms to keep the genome annotation always up-to-date; (iii) comparative genomic tools such as Genome-wide ORF Alignment (GOAL); and (iv) the Oral Pathogen Microarray Database. BROP can also handle unfinished genomic sequences and provides secure yet flexible control over data access. The concept of providing an integrated source of genomic data, as well as the data-mining model used in BROP can be applied to other organisms. BROP can be publicly accessed at http://www.brop.org. C1 Forsyth Inst, Boston, MA 02115 USA. RP Chen, T (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM tchen@forsyth.org FU NIDCR NIH HHS [K22 DE014742, K22 DE14742] NR 15 TC 27 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2005 VL 33 SU 2 BP W734 EP W740 DI 10.1093/nar/gki361 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GR UT WOS:000230271400151 PM 15980574 ER PT J AU Reche, PA Reinherz, EL AF Reche, PA Reinherz, EL TI PEPVAC: a web server for multi-epitope vaccine development based on the prediction of supertypic MHC ligands SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CLASS-I; PEPTIDE BINDING; HLA-A; POLYMORPHISM; MOLECULES; COMPLEXES AB Prediction of peptide binding to major histocompatibility complex (MHC) molecules is a basis for anticipating T-cell epitopes, as well as epitope discovery-driven vaccine development. In the human, MHC molecules are known as human leukocyte antigens ( HLAs) and are extremely polymorphic. HLA polymorphism is the basis of differential peptide binding, until now limiting the practical use of current epitope-prediction tools for vaccine development. Here, we describe a web server, PEPVAC ( Promiscuous EPitope-based VACcine), optimized for the formulation of multi-epitope vaccines with broad population coverage. This optimization is accomplished through the prediction of peptides that bind to several HLA molecules with similar peptide-binding specificity (supertypes). Specifically, we offer the possibility of identifying promiscuous peptide binders to five distinct HLA class I supertypes (A2, A3, B7, A24 and B15). We estimated the phenotypic population frequency of these supertypes to be 95%, regardless of ethnicity. Targeting these supertypes for promiscuous peptide-binding predictions results in a limited number of potential epitopes without compromising the population coverage required for practical vaccine design considerations. PEPVAC can also identify conserved MHC ligands, as well as those with a C-terminus resulting from proteasomal cleavage. The combination of these features with the prediction of promiscuous HLA class I ligands further limits the number of potential epitopes. The PEPVAC server is hosted by the Dana-Farber Cancer Institute at the site http://immunax.dfci.harvard.edu/PEPVAC/. C1 Harvard Univ, Sch Med, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reche, PA (reprint author), Harvard Univ, Sch Med, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM reche@research.dfci.harvard.edu; ellis_reinherz@dfci.harvard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900, R01 AI050900] NR 21 TC 32 Z9 32 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2005 VL 33 SU 2 BP W138 EP W142 DI 10.1093/nar/gki357 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GR UT WOS:000230271400025 PM 15980443 ER PT J AU Donelan, K Buerhaus, PL Ulrich, BT Norman, L Dittus, R AF Donelan, K Buerhaus, PL Ulrich, BT Norman, L Dittus, R TI Awareness and perceptions of the Johnson & Johnson campaign for nursing's future: Views from nursing students, RNs, and CNOs SO NURSING ECONOMICS LA English DT Article AB The authors examined the awareness and attitudes of nursing students, RNs, and CNOs about initiatives to address nursing recruitment and retention, specifically the Johnson & Johnson Campaign for Nursing's Future. Nursing students, RNs, and CNOs reported a high level of awareness of several key elements of the Johnson & Johnson Campaign - advertisements, recruitment materials, the discover nursing.com Web site, and regional "Promise of Nursing" fundraising events. The immediate and far reach of this Campaign is both visible and perceived to have a positive impact on several dimensions. Nursing students, RNs in practice, and nurses in leadership see the Campaign through different lenses, with each emphasizing different issues of importance. The Campaign remains an ambitious and unique example of private sector involvement in helping address the current and projected future nursing shortage. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Donelan, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JUL-AUG PY 2005 VL 23 IS 4 BP 150 EP + PG 8 WC Nursing SC Nursing GA 046HL UT WOS:000237802100002 PM 16189979 ER PT J AU Giuliano, KK Tyer-Viola, L Lopez, RP AF Giuliano, KK Tyer-Viola, L Lopez, RP TI Unity of knowledge in the advancement of nursing knowledge SO NURSING SCIENCE QUARTERLY LA English DT Article DE knowledge development; paradigm; warrantable evidence; worldview ID SCIENCE; PARADIGMS AB During the past 20 years, we have witnessed an explosion in nursing knowledge providing the discipline with diverse and multifaceted theoretical frameworks and paradigms. One knowledge theme that pervades the dialogue in the scholarly literature is that of multiple ways of knowing. With the acknowledgement that the fundamental nature of nursing knowledge is grounded in the understanding of human nature and its response to its environment, comes an imperative for a consilience of knowledge. The purpose of this article is to present such a unified worldview by articulating a vision of nursing knowledge, a meaning of unity of knowledge, and a challenge to the discipline to embrace inclusive rather than exclusive ways of knowing. C1 Philips Med Syst, Andover, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Giuliano, KK (reprint author), Philips Med Syst, Andover, MA USA. NR 37 TC 1 Z9 3 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD JUL PY 2005 VL 18 IS 3 BP 243 EP 248 DI 10.1177/0894318405277527 PG 6 WC Nursing SC Nursing GA 937CZ UT WOS:000229903500012 PM 15976047 ER PT J AU Buras, J Reenstra, WR Orlow, D Horton, ES Veves, A AF Buras, J Reenstra, WR Orlow, D Horton, ES Veves, A TI Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes SO OBESITY RESEARCH LA English DT Article DE adiponectin; troglitazone; receptor for advanced glycation end-products; endothelial function; vascular reactivity ID INSULIN-RESISTANCE; VASCULAR FUNCTION; RECEPTOR; HYPOADIPONECTINEMIA; EXPRESSION; ADIPOSE; RISK; SENSITIVITY; DYSFUNCTION; ADIPOCYTES AB Objective: Adiponectin has been proposed to be related to endothelial function. We have examined the relationship between the increase in adiponectin levels that is associated with troglitazone treatment and endothelium-dependent vasodilation in type 2 diabetic patients. Research Methods and Procedures: Seventy-two patients participated in this randomized, placebo-controlled, double-blinded study. High-resolution ultrasound images were used to measure the flow-mediated dilation (endothelium-dependent) and nitroglycerin-induced dilation (endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was employed to measure the vascular reactivity in the forearm skin. Results: Troglitazone treatment resulted in an average 75% increase in the adiponectin levels, but no changes were observed in the endothelium-dependent vasodilation, any other, measurement of vascular reactivity, or any other markers of endothelial activation. Also, no changes were observed in the expression of the receptor for advanced glycation end-products in skin biopsies taken from the forearm. Significant correlations were observed during troglitazone treatment between the changes in the adiponectin levels and the changes in fasting plasma glucose (r = -0.29, p < 0.05), hemoglobin A, (r = -0.30, p < 0.05), total cholesterol (r = 0.25, p < 0.05), and low-density lipoprotein-cholesterol (r = 0.34, p < 0.01). Discussion: The increase in adiponectin levels after troglitazone treatment is not associated with an improvement in the endothelium-dependent vasodilation, indicating that adiponectin is not a major determinant of endothelial function. In addition, receptor for advanced glycation end-products expression in the skin microcirculation is not affected by troglitazone treatment. C1 Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU NCRR NIH HHS [RR 01032] NR 32 TC 7 Z9 7 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 2005 VL 13 IS 7 BP 1167 EP 1174 DI 10.1038/oby.2005.138 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 955GE UT WOS:000231212800007 PM 16076985 ER PT J AU Tracy, EE AF Tracy, EE TI What's a cervix? SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID HEALTH LITERACY; KNOWLEDGE; CARE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Founders 406,Fruit St, Boston, MA 02114 USA. EM EETracy@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2005 VL 106 IS 1 BP 190 EP 191 DI 10.1097/01.AOG.0000167388.21251.cc PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 939LF UT WOS:000230073500029 PM 15994636 ER PT J AU Stone, RM AF Stone, RM TI Farnesyl transferase inhibitors in myeloid disorders - The Lancet/Karp article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID MYELODYSPLASTIC SYNDROME; MULTICENTER PHASE-2; LEUKEMIA; R115777; ZARNESTRA(TM); ADULTS; TRIAL; AML C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 8 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 JUL PY 2005 VL 19 IS 8 BP 1049 EP 1050 PG 2 WC Oncology SC Oncology GA 052EM UT WOS:000238214300019 ER PT J AU Cremers, SL Ciolino, JB Ferrufino-Ponce, ZK Henderson, BA AF Cremers, SL Ciolino, JB Ferrufino-Ponce, ZK Henderson, BA TI Objective assessment of skills in intraocular surgery (OASIS) SO OPHTHALMOLOGY LA English DT Article ID CLINICAL-EVALUATION EXERCISE; LIMBAL RELAXING INCISIONS; CATARACT-SURGERY; SURGICAL COMPETENCE; TECHNICAL SKILLS; AMERICAN BOARD; RISK-FACTORS; PHACOEMULSIFICATION; ASTIGMATISM; OPHTHALMOLOGY AB Objective: To establish an objective ophthalmic surgical evaluation protocol to assess residents' surgical competency and improve residents' surgical outcomes. Participants: Eight experts in resident education from comprehensive ophthalmology, cornea, glaucoma, and retina services; 2 chief residents (postgraduate year 5 [PGY5]); and resident representatives from PGYs 2, 3, and 4 participated in the development of an objective assessment tool of skills in resident cataract surgery. Methods: Analysis of all resident cataract surgeries performed at our service from July 2001 to July 2003 led to the development of a 1-page objective evaluation form to assess residents' skills in cataract surgery. A panel of surgeons at the Massachusetts Eye and Ear Infirmary reviewed the database and the evaluation form and provided constructive feedback. Results: Development of a unique database of all resident cataract cases and constructive feedback by experts in resident teaching assisted in creating a 1-page evaluation form entitled Objective Assessment of Skills in Intraocular Surgery (OASIS). Conclusions: OASIS has face and content validity and can be used to assess, objectively, surgical events and surgical skill. We believe the OASIS evaluation form and database will be a valuable tool for assessing ophthalmology residents' surgical skills at other residency programs as well. (c) 2005 by the American Academy of Ophthalmology. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Cremers, SL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM sandra_cremers@meei.harvard.edu NR 28 TC 57 Z9 57 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2005 VL 112 IS 7 BP 1236 EP 1241 DI 10.1016/j.ophtha.2005.01.045 PG 6 WC Ophthalmology SC Ophthalmology GA 940CK UT WOS:000230121100012 PM 15922450 ER PT J AU Kump, LI Cervantes-Castaneda, RA Androudi, SN Foster, CS AF Kump, LI Cervantes-Castaneda, RA Androudi, SN Foster, CS TI Analysis of pediatric uveitis cases at a tertiary referral center SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 23-26, 2004 CL New Orleans, LA SP Amer Acad Ophthalmol ID VISUAL-LOSS; CHILDHOOD; CHILDREN; EPIDEMIOLOGY; PREVALENCE AB Objective: To analyze demographics, anatomic data, diagnoses, systemic associations, and visual outcomes of pediatric patients in a large tertiary eye center. Design: Retrospective cohort study. Methods: The records of 1242 patients with uveitis referred to the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary (MEEI) from 1985 to 2003 were reviewed retrospectively. Two hundred sixty-nine patients 16 years and younger were identified. Results: Among 269 children with uveitis, 53.5% were girls, 82% were Caucasian, and 82% were born in the United States. Mean age was 8 years (standard deviation, 3.8; range, 1-16). Anterior uveitis represented 56.9% of cases; intermediate, 20.8%; panuveitis, 16%; and posterior, 6.3%. Nongranulomatous (77.6%) and noninfectious (85.7%) were the most frequent types of inflammation. The process was bilateral in 74.4% of patients. Mean follow-up was 22 months, with mean age of 8 years at diagnosis. Mean duration of uveitis at the time of presentation at the MEEI was 2 years. The range of time between the diagnosis of uveitis and referral was 1 day to 5.6 years. The length of time between diagnosis of uveitis and the referral to the tertiary center strongly correlated with the complication rate and degree of visual impairment in our study. The longer the time before the patients were seen by the uveitis expert, the worse the visual outcomes. No systemic associations were found in 58% of patients, juvenile idiopathic arthritis was responsible for 33% of cases, 8% of patients had other systemic associations, and 1% had tubulointerstitial nephritis uveitis syndrome. Conclusions: Uveitis remains a serious cause of morbidity and visual loss in children. Timely referral to uveitis specialists in the tertiary referral centers may lead to improved visual outcomes in children with chronic uveitis. (c) 2005 by the American Academy of Ophthalmology. C1 Massachusetts Eye Res & Surg Inst, Boston, MA 02114 USA. Ocular Immunol & Uveitis Fdn, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, 100 Charles River Plaza,Suite 301, Boston, MA 02114 USA. EM fosters@uveitis.org NR 20 TC 81 Z9 86 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2005 VL 112 IS 7 BP 1287 EP 1292 DI 10.1016/j.ophtha.2005.01.044 PG 6 WC Ophthalmology SC Ophthalmology GA 940CK UT WOS:000230121100020 PM 15921752 ER PT J AU Chang, EL Hatton, MP Bernardino, CR Rubin, PAD AF Chang, EL Hatton, MP Bernardino, CR Rubin, PAD TI Simplified repair of zygomatic fractures through a transconjunctival approach SO OPHTHALMOLOGY LA English DT Article ID CALDWELL-LUC PROCEDURE; BUTTRESS RECONSTRUCTION; MALAR FRACTURES; FIXATION; COMPLEX; REDUCTION; BONE; MANAGEMENT; REGION AB Objective: To describe a simplified technique of zygomatic fracture repair. Design: Retrospective, noncomparative case series with description of a surgical technique. Participants: Twenty consecutive patients with zygomatic fractures undergoing repair with the described technique. Intervention: Fracture repair was accomplished with a technique that used a T-bar screw for reduction through a transconjunctival approach. Main Outcome Measure: Successful fracture reduction. Results: Twenty patients with zygomatic fractures underwent successful reduction with the simplified technique. No complications were observed. Conclusions: The use of the T-bar through a transconjunctival approach is a simplified and effective technique for zygomatic fracture repair. (c) 2005 by the American Academy of Ophthalmology. C1 Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Emory Univ, Sch Med, Ctr Eye, Atlanta, GA 30322 USA. RP Chang, EL (reprint author), Univ So Calif, Keck Sch Med, Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA. NR 33 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2005 VL 112 IS 7 BP 1302 EP 1309 DI 10.1016/j.ophtha.2005.01.053 PG 8 WC Ophthalmology SC Ophthalmology GA 940CK UT WOS:000230121100023 PM 15921754 ER PT J AU Slattery, WH Lev, TH Fisher, LM Connell, SS Lqbal, Z Go, LL AF Slattery, WH Lev, TH Fisher, LM Connell, SS Lqbal, Z Go, LL TI MRI evaluation of neurofibromatosis 2 patients: A standardized approach for accuracy in interpretation SO OTOLOGY & NEUROTOLOGY LA English DT Article DE acquisition protocol; internal auditory canal; magnetic resonance imaging; neurofibromatosis Type 2; vestibular schwannoma ID VESTIBULAR SCHWANNOMA AB Objective: To determine the level of agreement between local radiologists' and an experienced neuroradiologist's measurements of vestibular schwannomas. Study Design: Prospective study with uniform magnetic resonance acquisition protocol parameters and reporting instructions across 30 magnetic resonance imaging facilities worldwide. Setting: Multicenter natural history study of neurofibromatosis Type 2. Subjects: One hundred fifteen magnetic resonance imaging examinations of 57 neurofibromatosis Type 2 patients older than 5 years of age. Interventions: Thin-slice, postcontrast cranial magnetic resonance imaging. Main Outcome Measures: Spearman's rho interobserver association coefficient of vestibular schwannoma linear measurements. Results: The local and experienced radiologist measurements and identification of tumors agreement was fair (K = 0.77). Discordant interpretations were adjudicated by another experienced neuroradiologist. Conclusion: The least interobserver variability was found in measurements of thin-slice postcontrast magnetic resonance imaging scans obtained at neurofibromatosis Type 2 centers in patients without previous operations and moderately sized tumors. If the schwannoma was difficult to assess, because of magnetic resonance imaging acquisition protocol, postoperative changes, or tumors smaller than 5 mm in greatest diameter, the neuroradiologist provided a more thorough assessment. The authors suggest uniform reporting criteria for vestibular schwannoma assessments to ensure clinically relevant information is communicated regarding vestibular schwannoma size. C1 Univ Calif Los Angeles, Keck Sch Med, House Ear Inst, Los Angeles, CA 90057 USA. Univ Calif Los Angeles, Keck Sch Med, House Ear Clin, Los Angeles, CA 90057 USA. Univ Calif Los Angeles, Keck Sch Med, House Ear Inst, Dept Clin Studies, Los Angeles, CA 90057 USA. Univ Calif Los Angeles, Keck Sch Med, Dept Radiol & Otolaryngol, Los Angeles, CA 90057 USA. Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Slattery, WH (reprint author), Univ Calif Los Angeles, Keck Sch Med, House Ear Inst, 2100 W 3rd St,5th Floor, Los Angeles, CA 90057 USA. EM wslattery@hei.org NR 9 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2005 VL 26 IS 4 BP 733 EP 740 DI 10.1097/01.mao.0000169048.15889.80 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 957ZL UT WOS:000231412000032 PM 16015177 ER PT J AU Patton, KK Zacks, ES Chang, JY Shea, MA Ruskin, JN Macrae, CA Ellinor, PT AF Patton, KK Zacks, ES Chang, JY Shea, MA Ruskin, JN Macrae, CA Ellinor, PT TI Clinical subtypes of lone atrial fibrillation SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE lone atrial fibrillation; genetics; morbidity; arrhythmia ID RISK-FACTOR; NATURAL-HISTORY; STROKE; MECHANISMS; MUTATION; LOCUS; DEATH; HEART; KCNQ1 AB Aims: In the face of increasing evidence of underlying genetic heterogeneity for lone atrial fibrillation (LAF), we undertook a clinical analysis of subjects to identify the phenotypic subsets of this arrhythmia. Methods and Results: We evaluated serial patients who presented with LAF between July 5, 2001 and December 19, 2003. Subjects underwent a standardized interview to elicit a detailed medical history, prior therapies, and precipitants of atrial fibrillation. The results of a physical exam, electrocardiogram and echocardiogram were reviewed. One hundred and eighty subjects with a mean age of 45 years (15-67 years) at the time of diagnosis were enrolled. The majority of patients originally presented with paroxysmal fibrillation (94%), and 7.8% progressed to permanent AF. Reported triggers for AF included sleeping (44%), exercise (36%), alcohol use (36%), and eating (34%). Women with LAF had distinct symptoms, triggers for episodic AF, and over one-fourth had an underlying rheumatologic condition. Several subsets of AF including familial AF (39%), exercise-induced AF (32%), and conduction system disease requiring pacemaker implantation (7%), were identified. Conclusions: Family history, exercise as a trigger of AF, and a history of a pacemaker identified subtypes of LAF. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 FU NHLBI NIH HHS [HL-71632, R01 HL075431] NR 34 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2005 VL 28 IS 7 BP 630 EP 638 DI 10.1111/j.1540-8159.2005.00161.x PG 9 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 949RU UT WOS:000230806600005 PM 16008797 ER PT J AU Khasnis, A Jongnarangsin, K Abela, G Veerareddy, S Reddy, V Thakur, R AF Khasnis, A Jongnarangsin, K Abela, G Veerareddy, S Reddy, V Thakur, R TI Tachycardia-induced cardiomyopathy: A review of literature SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Review ID CONGESTIVE-HEART-FAILURE; ATRIAL-FIBRILLATION SUBSTRATE; VENTRICULAR SYSTOLIC DYSFUNCTION; RADIOFREQUENCY CATHETER ABLATION; INDUCED DILATED CARDIOMYOPATHY; TITIN ISOFORM EXPRESSION; SUPRAVENTRICULAR TACHYCARDIA; OXIDATIVE STRESS; CONTRACTILE DYSFUNCTION; NATRIURETIC-FACTOR C1 Michigan State Univ, Dept Internal Med, Div Cardiol, E Lansing, MI 48824 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thakur, R (reprint author), Ingham Reg Med Ctr, Thorac & Cardiovasc Inst, 405 Greenlawn Campus, Lansing, MI 48910 USA. EM thakur@msu.edu NR 101 TC 48 Z9 54 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2005 VL 28 IS 7 BP 710 EP 721 DI 10.1111/j.1540-8159.2005.00143.x PG 12 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 949RU UT WOS:000230806600017 PM 16008809 ER PT J AU Wang, SX Lim, G Yang, LL Zeng, Q Sung, B Martyn, JAJ Mao, JR AF Wang, SX Lim, G Yang, LL Zeng, Q Sung, B Martyn, JAJ Mao, JR TI A rat model of unilateral hindpaw burn injury: Slowly developing rightwards shift of the morphine dose-response curve SO PAIN LA English DT Article DE burn injury; allodynia; hyperalgesia; protein kinase C gamma; mu-opioid receptor; morphine; analgesia ID PROTEIN-KINASE-C; PERIPHERAL-NERVE INJURY; CORD DORSAL-HORN; SPINAL-CORD; NEUROPATHIC PAIN; SECONDARY HYPERALGESIA; THERMAL HYPERALGESIA; OPIOID SYSTEMS; UP-REGULATION; INCREASES AB Management of pain after burn injury is an unresolved clinical issue. In a rat model of hindpaw burn injury, we examined the effects of systemic morphine on nociceptive behaviors following injury. Injury was induced by immersing the dorsal part of one hindpaw into a hot water bath (85 degrees C) for 4, 7, or 12 s under pentobarbital anesthesia. Mechanical allodynia to von Frey filament stimulation and thermal hyperalgesia to radiant heat were assessed. Burn injury induced by the 12-s (but not 4-, or 7-s) hot water immersion resulted in reliable and lasting mechanical allodynia and thermal hyperalgesia evident by day 1. In addition, there was an upregulation of protein kinase C gamma and a progressive downregulation of mu-opioid receptors within the spinal cord dorsal horn ipsilateral to injury as revealed by immunohistochemistry and Western blot. In both injured and sham rats, the anti-nociceptive effects of subcutaneous morphine were examined on post-injury days 7 and 14. While the morphine AD50 dose was comparable on day 7 between burn (1.61 mg/kg) and control (1.7 mg/kg) rats, the morphine dose-response curve was shifted to the right in burn-injured rats (4.6 mg/kg) on post-injury day 14 as compared with both the injured rats on post-injury day 7 and sham rats on day 14 (1.72 mg/kg). These data indicate that hindpaw burn injury reliably produces persistent mechanical allodynia and thermal hyperalgesia and that the reduced efficacy of morphine anti-nociception in chronic burn injury may be in part due to a downregulation of spinal P-opioid receptors. (C) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Pain Ctr,Pain Res, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Pain Ctr,Pain Res, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIGMS NIH HHS [NIH GM31569, GM55082, R01 GM055082]; NINDS NIH HHS [NIH NS42661, NS45681] NR 36 TC 24 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2005 VL 116 IS 1-2 BP 87 EP 95 DI 10.1016/j.pain.2005.03.044 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 944PI UT WOS:000230440700012 PM 15936884 ER PT J AU Seefelder, C Sparks, JW Chirnomas, D Diller, L Shamberger, RC AF Seefelder, C Sparks, JW Chirnomas, D Diller, L Shamberger, RC TI Perioperative management of a child with severe hypertension from a catecholamine secreting neuroblastoma SO PEDIATRIC ANESTHESIA LA English DT Article DE neuroblastoma; catecholamines; pheochromocytoma; malignant hypertension; drugs; doxazosin ID MAGNESIUM-SULFATE; PHEOCHROMOCYTOMA; THERAPY; FAILURE AB Increased catecholamine secretion from neuroblastomas can occasionally be demonstrated, but severe hypertension is uncommon. We report the perioperative management of a 5 year old child with stage III adrenal neuroblastoma who presented with malignant hypertension and high norepinephrine and dopamine levels. Hypertensive crises occurred during anesthesia for surgical biopsy and during chemotherapy. After blood pressure control using phenoxybenzamine and enalapril, doxazosin was used successfully as the preoperative alpha-adrenergic receptor antagonist for surgical tumor resection. C1 Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Naval Med Ctr San Diego, Dept Anesthesia, San Diego, CA USA. Naval Med Ctr San Diego, Postoperat Unit, San Diego, CA USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Seefelder, C (reprint author), Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM christian.seefelder@childrens.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 20 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JUL PY 2005 VL 15 IS 7 BP 606 EP 610 DI 10.1111/j.1460-9592.2005.01631.x PG 5 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 935SO UT WOS:000229803900013 PM 15960647 ER PT J AU Sheridan, R AF Sheridan, R TI Outpatient burn care in the emergency department SO PEDIATRIC EMERGENCY CARE LA English DT Review DE bums; trauma; wounds ID MANAGEMENT; ESCHAROTOMY; CHILDREN C1 Shriners Hosp Children, Burn Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sumner Redstone Adult Burn Ctr, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Shriners Hosp Children, Burn Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM rsheridan@partners.org NR 13 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD JUL PY 2005 VL 21 IS 7 BP 449 EP 456 DI 10.1097/01.pec.0000169438.29315.fe PG 8 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 949GI UT WOS:000230772700009 PM 16027580 ER PT J AU Walor, DM Berdon, WE Westra, SJ AF Walor, DM Berdon, WE Westra, SJ TI 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease SO PEDIATRIC RADIOLOGY LA English DT Article DE cyanotic heart disease; skull; marrow expansion AB "Hair-on-end" skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. C1 Columbia Univ, Med Ctr, Dept Radiol, Childrens Hosp New York, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Berdon, WE (reprint author), Columbia Univ, Med Ctr, Dept Radiol, Childrens Hosp New York, 3959 Broadway, New York, NY 10032 USA. EM Web2@columbia.edu NR 7 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JUL PY 2005 VL 35 IS 7 BP 698 EP 701 DI 10.1007/s00247-005-1403-0 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 935SA UT WOS:000229802500009 PM 15776229 ER PT J AU Anupindi, S Perumpillichira, J Jaramillo, D Zalis, ME Israel, EJ AF Anupindi, S Perumpillichira, J Jaramillo, D Zalis, ME Israel, EJ TI Low-dose CT colonography in children: initial experience, technical feasibility, and utility (vol 35, pg 518, 2005) SO PEDIATRIC RADIOLOGY LA English DT Correction C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Gastroenterol & Nutr, Boston, MA 02115 USA. RP Anupindi, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 246, Boston, MA 02115 USA. EM sanupindi@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JUL PY 2005 VL 35 IS 7 BP 733 EP 733 DI 10.1007/s00247-005-1487-6 PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 935SA UT WOS:000229802500018 ER PT J AU Rothstein, DH Voss, SD Isakoff, M Puder, M AF Rothstein, DH Voss, SD Isakoff, M Puder, M TI Thymoma in a child: case report and review of the literature SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Review DE mediastinal mass; thymoma ID POSTOPERATIVE RADIOTHERAPY; MALIGNANT THYMOMA; THYMIC REGION; TUMORS; CLASSIFICATION AB Thymic lesions comprise approximately 2-3% of all pediatric mediastinal tumors and include thymic cysts, hyperplasia, carcinoma, and thymomas. Thymomas, which represent less than 1% of all mediastinal tumors, are rare mediastinal tumors in the pediatric population. Fewer than 30 cases in children have been described in the literature. These tumors are typically aggressive, with poor outcomes. We report a thymoma in a 14-year-old girl and review the available literature on thymomas and their treatment. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Puder, M (reprint author), Childrens Hosp, Dept Surg, NRB 11213,300 Longwood Ave, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu OI Rothstein, David/0000-0002-2045-9404 NR 21 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD JUL PY 2005 VL 21 IS 7 BP 548 EP 551 DI 10.1007/s00383-005-1419-4 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 965IE UT WOS:000231943000009 PM 15926048 ER PT J AU Binstadt, BA Levine, JC Nigrovic, PA Gauvreau, K Dedeoglu, F Fuhlbrigge, RC Weindling, SN Newburger, JW Sundel, RP AF Binstadt, BA Levine, JC Nigrovic, PA Gauvreau, K Dedeoglu, F Fuhlbrigge, RC Weindling, SN Newburger, JW Sundel, RP TI Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis SO PEDIATRICS LA English DT Article DE juvenile rheumatoid arthritis; Still's disease; Kawasaki disease; fever ID INTRAVENOUS GAMMA-GLOBULIN; RHEUMATOID-ARTHRITIS; KAWASAKI-DISEASE; LUPUS-ERYTHEMATOSUS; CARDIAC INVOLVEMENT; ACUTE-PHASE; ATHEROSCLEROSIS; CHILDREN; ASSOCIATION; DIAGNOSIS AB Objective. To evaluate coronary artery diameters among patients presenting with systemic-onset juvenile idiopathic arthritis (SoJIA). Methods. Fifty cases of SoJIA were reviewed. At the time of initial presentation with fever, 12 patients had echocardiograms that included a complete evaluation of the coronary arteries. A single reviewer measured the diameters of the left main, proximal left anterior descending, and proximal right coronary arteries. Body surface area- adjusted z scores were calculated with respect to a normative population. Results. Coronary artery dilation (z score: > 2) was observed for 5 of the 12 patients with SoJIA who had echocardiograms performed at the time of presentation with fever. No patient developed a coronary artery aneurysm, and all of the coronary artery z scores normalized within 4 months. Only 2 of the 5 patients with coronary artery z scores of > 2 fulfilled the clinical criteria for Kawasaki disease, the most commonly recognized cause of coronary artery dilation among children. Conclusions. Children presenting with SoJIA may have coronary artery dilation similar to that observed for children with Kawasaki disease. These data suggest that the presence of coronary artery dilation on initial echocardiograms for patients with fever does not exclude the diagnosis of SoJIA. C1 Childrens Hosp, Rheumatol Program, Div Immunol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Sundel, RP (reprint author), Childrens Hosp, Rheumatol Program, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM robert.sundel@childrens.harvard.edu RI Binstadt, Bryce/N-1305-2013; OI Binstadt, Bryce/0000-0003-3127-3856; Sundel, Robert/0000-0002-0083-5695 NR 23 TC 32 Z9 33 U1 0 U2 1 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 JUL PY 2005 VL 116 IS 1 BP E89 EP E93 DI 10.1542/peds.2004-2190 PG 5 WC Pediatrics SC Pediatrics GA 941IC UT WOS:000230207500013 PM 15930186 ER PT J AU Spencer, TJ Newcorn, JH Kratochvil, CJ Ruff, D Michelson, D Biederman, J AF Spencer, TJ Newcorn, JH Kratochvil, CJ Ruff, D Michelson, D Biederman, J TI Effects of atomoxetine on growth after 2-year treatment among pediatric patients with attention-deficit/hyperactivity disorder SO PEDIATRICS LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; growth; children; adolescents ID DEFICIT HYPERACTIVITY DISORDER; CHILDREN; HORMONE; STIMULATION; SECRETION; WEIGHT; HEIGHT AB Objective. Treatment for attention-deficit/ hyperactivity disorder is maintained typically over periods of months or years and, as a result, the potential effects on growth of pharmacotherapy for this disorder have been an area of concern. This meta-analysis examined the effect on growth of atomoxetine, now approved in the United States for the treatment of attention-deficit/hyperactivity disorder. Methods. Patients (N = 412) were 6 to 16 years of age at the start of the treatment period and received atomoxetine treatment (maximal dose: 1.8 mg/ kg per day) for >= 2 years. Weight and height measurements were analyzed both as actual values and after conversion to percentiles and z scores with growth charts from the Centers for Disease Control and Prevention. Expected weight and height at the end point were calculated through extrapolation from patients' baseline percentiles with the growth charts. Results. Results indicated that, after 2 years, observed weight and height were close to those predicted on the basis of the patients' baseline weight and height. Weight increased an average of 10.8 kg, a decrease relative to baseline normative weight of 2.7 percentiles, corresponding to 0.87 kg. Height increased an average of 13.3 cm, a decrease relative to baseline normative heights of 2.2 percentiles, corresponding to 0.44 cm. For both weight and height, the quartile of patients who were smallest at baseline had an increase in end- point percentile, whereas patients in the highest quartile had a decrease. Conclusions. These findings suggested that, at the group level, there was only a minimal effect on height after 2 years of treatment with atomoxetine and, for patients most at risk (the lowest quartile), there seemed to be no effect. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 725, Boston, MA 02114 USA. EM tspencer@partners.org OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 24 TC 33 Z9 33 U1 1 U2 1 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 JUL PY 2005 VL 116 IS 1 BP E74 EP E80 DI 10.1542/peds.2004-0624 PG 7 WC Pediatrics SC Pediatrics GA 941IC UT WOS:000230207500011 PM 15995021 ER PT J AU Million, M Maillot, C Adelson, DA Nozu, T Gauthier, A Rivier, J Chrousos, GP Bayati, A Mattsson, H Tache, Y AF Million, M Maillot, C Adelson, DA Nozu, T Gauthier, A Rivier, J Chrousos, GP Bayati, A Mattsson, H Tache, Y TI Peripheral injection of sauvagine prevents repeated colorectal distension-induced visceral pain in female rats SO PEPTIDES LA English DT Article DE antalarmin; sauvagine; CRF; visceral pain; colorectal distension; female Fisher rats ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; RECEPTOR ANTAGONIST; UROTENSIN-I; RECTAL DISTENSION; CRF1 RECEPTOR; PARAVENTRICULAR NUCLEUS; TYPE-1 RECEPTOR; NMDA RECEPTORS; FOS EXPRESSION AB We investigated the effects of peripheral injection of sauvagine, a CRF(2) > CRF(1) receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced visceromotor response (VMR) measured as area under the curve (AUC) of abdominal muscle contraction in conscious female rats. Sauvagine (10 or 20 mu g/kg, s.c.) abolished the 226.7 +/- 64.3 % and 90.4 +/- 38.1 % increase in AUC to the 2nd CRD compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague-Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist, antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further the AUC by 33.5 +/- 23.3 % and 63.5 +/- 7.2 %, respectively in Fisher rats. These data suggest that peripheral CRF receptor activation exerts antinociceptive effects on CRD-induced visceral pain, whereas CRF(1) contributes to visceral sensitization. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, CURE, VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Div Digest Dis,Ctr Neurovisceral Sci & Womens Hlt, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, San Diego, CA 92186 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. AstraZeneca R&D, S-43183 Molndal, Sweden. RP Million, M (reprint author), Univ Calif Los Angeles, CURE, VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmuluget@ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [DK-57238-01A1S1, R01 DK-33061, R01 DK-57238, P50 DK 64539, DK26741] NR 70 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2005 VL 26 IS 7 BP 1188 EP 1195 DI 10.1016/j.peptides.2005.02.004 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 940PE UT WOS:000230155600012 PM 15949637 ER PT J AU Borodic, G Bartley, M Slattery, W Glasscock, M Johnson, E Malazio, C Goodnough, M Acquadro, M McKenna, M AF Borodic, G Bartley, M Slattery, W Glasscock, M Johnson, E Malazio, C Goodnough, M Acquadro, M McKenna, M TI Botulinum toxin for aberrant facial nerve regeneration: Double-blind, placebo-controlled trial using subjective Endpoints SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PRIMARY HEADACHE DISORDERS; PALSY; PARALYSIS; EFFICACY AB Background: Aberrant facial nerve regeneration syndrome is systematically studied by constructing a subjective questionnaire organ nized into pertinent domains (impairment of quality of life, social interactions, perception of self-appearance, visual function, and perception of problem severity) and by physical assessment of degree of involuntary palpebral fissure closure during routine facial movements using videotaping and a physicians' grading scale. Methods: The videotape measurements Of corneal light reflex to upper lid margin distance and vertical palpebral distance were made during adynamic and active facial expression. Thirty-six. patients were studied (six in an open-label pilot study design and 30 in a multicenter, double-blind, placebo-controlled trial). Botulinum toxin type A injecdons consistently suppressed the degree of involuntary eyelid movement associated with smiling, chewing, and puckering by each measurement and in both study designs. Results: In all subjective morbidity domains, improvement was demonstrated in the double-blind study design (quality of life, p < 0.05; social interaction, p < 0.001; personal appearance, p < 0.001; peripheral visual impairment, p < 0.01; and perception of sever-ity, P < 0.05). Correlation between degrees of physical impairment, was significant but low comparing degree of subjective impairment to direct videotaped measurements. Correlation was more significant comparing subjective scores to the physicians' grading scale assessment of degree of physical impairment. Conclusions: Impairment in quality of life, social interactions, and self-assessment of appearance closely reflected the nature of the morbidity associated with palpebral fissure asymmetry associated with aberrant facial nerve regeneration. The physicians' grading scale best reflected subjective morbidity over direct video-taped measurements. C1 Massachusetts Eye & Ear Infirm, Boston, MA USA. House Ear Clin, Los Angeles, CA USA. Baptist Hosp, Nashville, TN USA. Univ Wisconsin, Food Res Div, Madison, WI 53706 USA. RP Borodic, G (reprint author), Beyer Townsend & Borodic PC, 100 Charles River Plaza, Boston, MA 02114 USA. NR 26 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2005 VL 116 IS 1 BP 36 EP 43 DI 10.1097/01.PRS.0000169689.27829.C4 PG 8 WC Surgery SC Surgery GA 942AA UT WOS:000230254100006 PM 15988245 ER PT J AU Dybbs, M Ngai, J Kaplan, JM AF Dybbs, M Ngai, J Kaplan, JM TI Using microarrays to facilitate positional cloning: Identification of tomosyn as an inhibitor of neurosecretion SO PLOS GENETICS LA English DT Article ID NONSENSE-MEDIATED DECAY; MESSENGER-RNA DECAY; PREMATURE TERMINATION CODONS; TOUCH RECEPTOR NEURONS; CAENORHABDITIS-ELEGANS; C-ELEGANS; GENE-EXPRESSION; SYNAPTIC-TRANSMISSION; NEUROTRANSMITTER RELEASE; INSERTIONAL MUTAGENESIS AB Forward genetic screens have been used as a powerful strategy to dissect complex biological pathways in many model systems. A significant limitation of this approach has been the time-consuming and costly process of positional cloning and molecular characterization of the mutations isolated in these screens. Here, the authors describe a strategy using microarray hybridizations to facilitate positional cloning. This method relies on the fact that premature stop codons (i.e., nonsense mutations) constitute a frequent class of mutations isolated in screens and that nonsense mutant messenger RNAs are efficiently degraded by the conserved nonsense-mediated decay pathway. They validate this strategy by identifying two previously uncharacterized mutations: (1) tom-1, a mutation found in a forward genetic screen for enhanced acetylcholine secretion in Coenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1 transcription factor gene. They further demonstrate the broad applicability of this strategy using other known mutants in C. elegans, Arabidopsis, and mouse. Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter secretion. These results also suggest that microarray hybridizations have the potential to significantly reduce the time and effort required for positional cloning. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Calif Berkeley, Helen Wills Neurosci Inst, Funct Genom Lab, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM054728] NR 69 TC 32 Z9 37 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2005 VL 1 IS 1 BP 6 EP 16 AR e2 DI 10.1371/journal.pgen.0010002 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 998CP UT WOS:000234295900003 PM 16103915 ER PT J AU Li, X Li, WH Wang, H Cao, J Maehashi, K Huang, LQ Bachmanov, AA Reed, DR Legrand-Defretin, V Beauchamp, GK Brand, JG AF Li, X Li, WH Wang, H Cao, J Maehashi, K Huang, LQ Bachmanov, AA Reed, DR Legrand-Defretin, V Beauchamp, GK Brand, JG TI Pseudogenization of a sweet-receptor gene accounts for cats' indifference toward sugar SO PLOS GENETICS LA English DT Article ID CANDIDATE TASTE RECEPTOR; SACCHARIN PREFERENCE; SPECIES DIFFERENCES; POSITIONAL CLONING; LOCUS SAC; TAS1R3; IDENTIFICATION; PHYLOGENY; RESPONSES; NEURONS AB Although domestic cats (Felis silvestris catus) possess an otherwise functional sense of taste, they, unlike most mammals, do not prefer and may be unable to detect the sweetness of sugars. One possible explanation for this behavior is that cats lack the sensory system to taste sugars and therefore are indifferent to them. Drawing on work in mice, demonstrating that alleles of sweet-receptor genes predict low sugar intake, we examined the possibility that genes involved in the initial transduction of sweet perception might account for the indifference to sweet-tasting foods by cats. We characterized the sweet-receptor genes of domestic cats as well as those of other members of the Felidae family of obligate carnivores, tiger and cheetah. Because the mammalian sweet-taste receptor is formed by the dimerization of two proteins (T1R2 and T1R3; gene symbols Tas1r2 and Tas1r3), we identified and sequenced both genes in the cat by screening a feline genomic BAC library and by performing PCR with degenerate primers on cat genomic DNA. Gene expression was assessed by RT-PCR of taste tissue, in situ hybridization, and immunohistochemistry. The cat Tas1r3 gene shows high sequence similarity with functional Tas7r3 genes of other species. Message from Tas1r3 was detected by RT-PCR of taste tissue. In situ hybridization and immunohistochemical studies demonstrate that Tas1r3 is expressed, as expected, in taste buds. However, the cat Tas1r2 gene shows a 247-base pair microdeletion in exon 3 and stop codons in exons 4 and 6. There was no evidence of detectable mRNA from cat Tas1r2 by RT-PCR or in situ hybridization, and no evidence of protein expression by immunohistochemistry. Tas1r2 in tiger and cheetah and in six healthy adult domestic cats all show the similar deletion and stop codons. We conclude that cat Tas7r3 is an apparently functional and expressed receptor but that cat Tas1r2 is an unexpressed pseudogene. A functional sweet-taste receptor heteromer cannot form, and thus the cat lacks the receptor likely necessary for detection of sweet stimuli. This molecular change was very likely an important event in the evolution of the cat's carnivorous behavior. C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Waltham Ctr Pet Nutr, Melton Mowbray, Leics, England. Univ Penn, Sch Arts & Sci, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Anat, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Brand, JG (reprint author), Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. EM brand@monell.org OI Bachmanov, Alexander/0000-0002-2861-3322; Reed, Danielle/0000-0002-4374-6107 FU NIDCD NIH HHS [T32 DC000014, R01 DC000882, R01 DC004698, R03 DC005154]; NIDDK NIH HHS [R01 DK025759] NR 40 TC 136 Z9 147 U1 5 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2005 VL 1 IS 1 BP 27 EP 35 AR e3 DI 10.1371/journal.pgen.0010003 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 998CP UT WOS:000234295900005 PM 16103917 ER PT J AU Dahia, PLM Ross, KN Wright, ME Hayashida, CY Santagata, S Barontini, M Kung, AL Sanso, G Powers, JF Tischler, AS Hodin, R Heitritter, S Moore, F Dluhy, R Sosa, JA Ocal, IT Benn, DE Marsh, DJ Robinson, BG Schneider, K Garber, J Arum, SM Korbonits, M Grossman, A Pigny, P Toledo, SPA Nose, V Li, C Stiles, CD AF Dahia, PLM Ross, KN Wright, ME Hayashida, CY Santagata, S Barontini, M Kung, AL Sanso, G Powers, JF Tischler, AS Hodin, R Heitritter, S Moore, F Dluhy, R Sosa, JA Ocal, IT Benn, DE Marsh, DJ Robinson, BG Schneider, K Garber, J Arum, SM Korbonits, M Grossman, A Pigny, P Toledo, SPA Nose, V Li, C Stiles, CD TI A HIF1 alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas SO PLOS GENETICS LA English DT Article ID HIPPEL-LINDAU PROTEIN; INDUCIBLE FACTOR-ALPHA; COMPLEX-II; SUCCINATE-DEHYDROGENASE; RESPIRATORY-CHAIN; HIF-ALPHA; HEREDITARY PARAGANGLIOMA; FAMILIAL PARAGANGLIOMA; ENZYMATIC-ACTIVITY; OXIDATIVE STRESS AB Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits 8 (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1 alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1 alpha activity in tumors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Ninos Dr Ricardo Gutierrez, Ctr Endocrine Invest, Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. St Bartholomews Hosp, London, England. Reg Univ Hosp, Lille, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Dahia, PLM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med & Cellular & Struct Biol, San Antonio, TX 78284 USA. EM Patricia_Dahia@dfci.harvard.edu RI Santagata, Sandro/A-7714-2009; Marsh, Deborah/I-1491-2014 OI Marsh, Deborah/0000-0001-5899-4931 FU NCI NIH HHS [R01 CA048017]; NINDS NIH HHS [R01 NS037685] NR 43 TC 238 Z9 243 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2005 VL 1 IS 1 BP 72 EP 80 AR e8 DI 10.1371/journal.pgen.0010008 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 998CP UT WOS:000234295900009 PM 16103922 ER PT J AU Rodriguez, WR Christodoulides, N Floriano, PN Graham, S Mohanty, S Dixon, M Hsiang, M Peter, T Zavahir, S Thior, I Romanovicz, D Bernard, B Goodey, AP Walker, BD McDevitt, JT AF Rodriguez, WR Christodoulides, N Floriano, PN Graham, S Mohanty, S Dixon, M Hsiang, M Peter, T Zavahir, S Thior, I Romanovicz, D Bernard, B Goodey, AP Walker, BD McDevitt, JT TI A microchip CD4 counting method for HIV monitoring in resource-poor settings SO PLOS MEDICINE LA English DT Article ID T-LYMPHOCYTE ENUMERATION; DEVELOPING-COUNTRIES; LIMITED RESOURCES; VIRAL LOAD; MICROSPHERES; INFECTION; CYTOMETRY; SYSTEM; HEALTH; RISK AB Background More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. Methods and Findings Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r=0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. Conclusion Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. Princess Marina Hosp, Botswana HArvard AIDS Inst Partnership, Gaborone, Botswana. RP Rodriguez, WR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. EM wrodriguez@partners.org; mcdevitt@mail.utexas.edu RI Mohanty, Sanghamitra/D-1122-2015; McDevitt, John/P-4108-2014 OI Mohanty, Sanghamitra/0000-0001-6601-944X; Graham, Susan/0000-0001-7847-8686; McDevitt, John/0000-0001-8789-9351 NR 30 TC 132 Z9 135 U1 0 U2 13 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 JUL PY 2005 VL 2 IS 7 BP 663 EP 672 AR e182 DI 10.1371/journal.pmed.0020182 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 953LJ UT WOS:000231077500016 PM 16013921 ER PT J AU Sohn, L Harada, ND AF Sohn, L Harada, ND TI Knowledge and use of preventive health practices among Korean women in Los Angeles county SO PREVENTIVE MEDICINE LA English DT Article DE health services; preventive health practices; acculturation; Asian American Pacific Islander; Korean American ID AMERICAN WOMEN; ASIAN-AMERICANS; PAP-SMEAR; MAMMOGRAPHY; PREDICTORS; BEHAVIORS; INSURANCE; ATTITUDES; SERVICES; CARE AB Background. The aims of this study are to determine (1) knowledge and use of preventive health practices, and (2) the relationship between acculturation and preventive health practices, in Korean women. Methods. The data came from the 2000 Korean American Health Survey (KAHS), which includes 656 women. The dependent variables included use of pap smears, physical examinations and mammograms, and use and knowledge of self-breast examinations. Independent variables included demographic and acculturation variables. Logistic regression modeling was used to assess the role of acculturation on dependent variables. Results. Some of the acculturation variables significantly predicted preventive practices. Being married (P < 0.0001) and insured (P < 0.05) were significantly associated with receipt of preventive services. A married Korean woman was more likely than an unmarried Korean woman to have a pap smear within 2 years (P < 0.0001), physical exam within 1 year (P < 0.0001), and perform self-breast examinations (P < 0.05). Conclusions. Factors related to acculturation influence use of preventive health practices by Korean American women, highlighting the need to consider cultural background in developing systems of care. Published by Elsevier Inc. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90024 USA. RP Sohn, L (reprint author), VA Greater Los Angeles Healthcare Syst, 11G 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Linda.sohn@med.va.gov NR 29 TC 22 Z9 22 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 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2005 VL 41 IS 1 BP 167 EP 178 DI 10.1016/j.ypmed.2004.09.039 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 933RY UT WOS:000229651800023 PM 15917008 ER PT J AU Koenigsberg, HW Buchsbaum, MS Buchsbaum, BR Schneiderman, JS Tang, CY New, A Goodman, M Siever, LJ AF Koenigsberg, HW Buchsbaum, MS Buchsbaum, BR Schneiderman, JS Tang, CY New, A Goodman, M Siever, LJ TI Functional MRI of visuospatial working memory in schizotypal personality disorder: a region-of-interest analysis SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; SCHIZOPHRENIC SUBJECTS; PERFORMANCE; TASK; FMRI; DYSFUNCTION; RECOGNITION; ACTIVATION; WORDS AB Background. Functional MRI studies have begun to identify neural networks implicated in visuo-spatial working memory in healthy volunteers and patients with schizophrenia. The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum. Method. Unmedicated patients with SPD by DSM-IV criteria and normal controls were assessed with fMRI while performing a visuospatial working-memory task. It required the subjects to retain the location of three dots located on the circumference of an imaginary circle and then respond to a query display in which one dot was presented and the subject required to press a button to indicate whether the probe dot location was previously displayed. Subject groups did not differ significantly in spatial memory scores. The exact Talairach and Tournoux coordinates of brain areas previously reported to show activation with spatial memory tasks were assessed. Results. The majority of these locations showed BOLD response activation significantly less in patients during the memory retention period, including the left ventral prefrontal cortex, superior frontal gyrus, intraparietal cortex and posterior inferior gyrus. Regions in the right middle prefrontal and prestriate cortex showed greater activation at a trend level for patients with SPD than for normal controls. In addition, we replicated the findings of increased activation with the task in healthy volunteers in the premotor areas, ventral prefrontal cortex and parietal cortex. Conclusions. SPD patients show decreased activation compared to healthy volunteers in key frontal regions and we also provided a partial replication of findings reported in healthy subjects. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. RP Koenigsberg, HW (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge, Bronx, NY 10468 USA. EM harold.koenigsberg@med.va.gov RI Schneiderman, Jason/E-1528-2013 OI Schneiderman, Jason/0000-0002-9313-0415 FU NCRR NIH HHS [5M01 RR00071] NR 31 TC 20 Z9 20 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2005 VL 35 IS 7 BP 1019 EP 1030 DI 10.1017/S0033291705004393 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EN UT WOS:000231500000010 PM 16045068 ER PT J AU Hanlon, FM Miller, GA Thoma, RJ Irwin, J Jones, A Moses, SN Huang, MX Weisend, MP Paulson, KM Edgar, JC Adler, LE Canive, JM AF Hanlon, FM Miller, GA Thoma, RJ Irwin, J Jones, A Moses, SN Huang, MX Weisend, MP Paulson, KM Edgar, JC Adler, LE Canive, JM TI Distinct M50 and M100 auditory gating deficits in schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Article DE auditory sensory gating; schizophrenia; M50; M100; magnetoencephalography ID EVOKED MAGNETIC-FIELDS; TEMPORAL GYRUS VOLUME; P50 SUPPRESSION; NEUROPHYSIOLOGICAL EVIDENCE; 1ST-EPISODE SCHIZOPHRENIA; RESPONSE SUPPRESSION; PREFRONTAL CORTEX; LEFT-HEMISPHERE; MEG; RELIABILITY AB The time course of the schizophrenia auditory gating deficit may provide clues to mechanisms of impaired cognition. Magnetoencephalography was recorded during a standard paired-click paradigm. Using source strength of the M50 and M100 components for each click, calculated from dipole locations identified as underlying each component for the first click, a ratio of the second divided by the first was used to measure gating. Patients showed a left-hemisphere gating deficit in M50 and a bilateral gating deficit in M100. Hypothesizing that an early deficit may affect later processing, hierarchical regression was used to examine variance shared between the components. A left-hemisphere M100 gating deficit was coupled with the left M50 gating deficit. In contrast, a right-hemisphere M 100 gating deficit was unrelated to M50 gating in either hemisphere. Investigations of interhemisphere gating relations may clarify group differences in regional connectivity and their role in gating. C1 New Mexico VA Hlth Care Syst, Ctr Funct Brain Imaging, Albuquerque, NM USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Mental Illness & Neurosci Discovery Inst Imaging, Albuquerque, NM USA. Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. Univ Illinois, Dept Psychiat, Urbana, IL 61801 USA. Univ Illinois, Beckman Inst, Biomed Imaging Ctr, Urbana, IL 61801 USA. New Mexico VA Hlth Care Syst, Dept Psychiat, Albuquerque, NM 87108 USA. Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. VA Hlth Care Syst, San Diego, CA USA. New Mexico VA Hlth Care Syst, Dept Radiol, Albuquerque, NM USA. Denver VA Med Ctr, Dept Psychiat, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Canive, JM (reprint author), VAMC, New Mexico VA Hlth Care Syst, 116A,1501 San Pedro SE, Albuquerque, NM 87108 USA. EM Jose.Canive@med.va.gov FU NIMH NIH HHS [R01 MH65304] NR 66 TC 50 Z9 54 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUL PY 2005 VL 42 IS 4 BP 417 EP 427 DI 10.1111/j.1469-8986.2005.00299.x PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 950QY UT WOS:000230873500006 PM 16008770 ER PT J AU Milad, MR Orr, SP Pitman, RK Rauch, SL AF Milad, MR Orr, SP Pitman, RK Rauch, SL TI Context modulation of memory for fear extinction in humans SO PSYCHOPHYSIOLOGY LA English DT Article DE fear renewal; reinstatement; extinction recall; fear conditioning; skin conductance ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; CONDITIONED FEAR; POTENTIATED STARTLE; SPONTANEOUS-RECOVERY; FACIAL EXPRESSIONS; EXTINGUISHED FEAR; EXPOSURE THERAPY; RELEVANT STIMULI; VIETNAM VETERANS AB Distinct memories are formed during fear conditioning and subsequent extinction. In animals, the expression of the latter is gated by the context. The recall of extinction memory after a long delay, and the contextual modulation thereof, has not been directly tested in humans. Mentally healthy volunteers underwent a 2-day fear conditioning and extinction protocol that examined the recall of extinction memory and its relationship to context. Conditioned stimuli were paired with an aversive electric shock in one visual context and extinguished in a different context. Extinction recall and renewal were examined 24 h after training. We found that skin conductance responses were small when the conditioned stimulus was presented in the extinction context, but responses were renewed when the conditioned stimulus was presented in the conditioning context. This finding demonstrates context dependency of extinction recall in humans. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. RP Rauch, SL (reprint author), Dept Psychiat, 149 13th St,CNY 2618, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu NR 83 TC 119 Z9 123 U1 3 U2 47 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUL PY 2005 VL 42 IS 4 BP 456 EP 464 DI 10.1111/j.1469-8986.2005.00302.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 950QY UT WOS:000230873500010 PM 16008774 ER PT J AU Simon, NM Parker, SW Wernick-Robinson, M Oppenheimer, JE Hoge, EA Worthington, JJ Korbly, NB Pollack, MH AF Simon, NM Parker, SW Wernick-Robinson, M Oppenheimer, JE Hoge, EA Worthington, JJ Korbly, NB Pollack, MH TI Fluoxetine for vestibular dysfunction and anxiety: A prospective pilot study SO PSYCHOSOMATICS LA English DT Article ID BALANCE DISORDERS; DIZZINESS; NUCLEUS; RAT; 5-HYDROXYTRYPTAMINE; HYPOTHESIS; MOBILITY; NEURONS AB Anxiety states and disorders amplify the symptoms and impairment associated with vestibular dysfunction. Five patients with inner ear vestibular dysfunction and anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and received an extensive battery of assessments at baseline and after 12 weeks of treatment. Fluoxetine led to significant or near significant reductions in anxiety measures and in impairment due to dizziness; improvements in clinical balance function and vestibular function were less clear The data add to the literature suggesting a role for selective serotonin reuptake inhibitors in the treatment of dizziness and anxiety. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 29 TC 20 Z9 20 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2005 VL 46 IS 4 BP 334 EP 339 DI 10.1176/appi.psy.46.4.334 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 940CF UT WOS:000230120600006 PM 16000676 ER PT J AU Hardin, JM Woodby, LL Crawford, MA Windsor, RA Miller, TM AF Hardin, JM Woodby, LL Crawford, MA Windsor, RA Miller, TM TI Data collection in a multisite project: Teleform (TM) SO PUBLIC HEALTH NURSING LA English DT Article DE AHRQ guideline; automated forms processing; data validation; Medicaid maternity care; Teleform (TM) ID DATA-ENTRY; FORMS AB Data collection, entry, validation, and management are salient time- and resource-consuming dimensions of all research projects. This is especially true for multisite studies, which pose unique, additional challenges because of their research design requirements. To save time and reduce the number of manual data entry errors, automated processing systems are becoming more widely used. Our research team chose Teleform(TM) for data entry and collection for the Smoking Cessation or Reduction in Pregnancy Trial study. This article presents our experience with this new technology. C1 Univ Alabama, Dept Informat Syst Stat & Management, Culverhouse Coll Commerce, Tuscaloosa, AL 35487 USA. Univ Alabama, Dept Family & Community Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, Washington, DC USA. Alabama Dept Publ Hlth, Bur Family Hlth Sci, Montgomery, AL 36102 USA. RP Hardin, JM (reprint author), Univ Alabama, Dept Informat Syst Stat & Management, Culverhouse Coll Commerce, 300 Alston Hall,Box 870226, Tuscaloosa, AL 35487 USA. EM mhardin@cba.ua.edu NR 12 TC 8 Z9 8 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD JUL-AUG PY 2005 VL 22 IS 4 BP 366 EP 370 DI 10.1111/j.0737-1209.2005.220410.x PG 5 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 959IA UT WOS:000231510200013 PM 16150019 ER PT J AU Zalis, ME Barish, MA Choi, JR Dachman, AH Fenlon, HM Ferrucci, JT Glick, SN Laghi, A Macari, M McFarland, EG Morrin, MM Pickhardt, PJ Soto, J Yee, J AF Zalis, ME Barish, MA Choi, JR Dachman, AH Fenlon, HM Ferrucci, JT Glick, SN Laghi, A Macari, M McFarland, EG Morrin, MM Pickhardt, PJ Soto, J Yee, J CA Working Grp Virtual Colonoscopy TI CT colonography reporting and data system: A consensus proposal SO RADIOLOGY LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; COLONIC POLYPS; FOLLOW-UP; SURVEILLANCE; NEOPLASIA; ADENOMA; LESIONS C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Mater Misericordiae Hosp, Dept Radiol, Dublin 7, Ireland. Boston Univ, Ctr Med, Dept Radiol, Boston, MA 02215 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Roma La Sapienza, Dept Radiol Sci, Rome, Italy. NYU, Ctr Med, Dept Radiol, New York, NY USA. St Lukes Hosp, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Univ Wisconsin, Ctr Med, Dept Radiol, Madison, WI USA. Univ Calif San Francisco, San Francisco VA Hosp, Ctr Med, Dept Radiol, San Francisco, CA 94143 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol White 270, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. EM mzalis@partners.org RI Morrin, Maureen/F-2010-2011; Laghi, Andrea/A-2343-2011; OI Laghi, Andrea/0000-0002-3091-7819; Soto, Jorge/0000-0003-2533-3015 NR 36 TC 339 Z9 346 U1 2 U2 9 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 JUL PY 2005 VL 236 IS 1 BP 3 EP 9 DI 10.1148/radiol.2361041926 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937DR UT WOS:000229905300002 PM 15987959 ER PT J AU Lembcke, A Borges, AC Dushe, S Dohmen, PM Wiese, TH Rogalla, P Hermann, KGA Hamm, B Enzweiler, CNH AF Lembcke, A Borges, AC Dushe, S Dohmen, PM Wiese, TH Rogalla, P Hermann, KGA Hamm, B Enzweiler, CNH TI Assessment of mitral valve regurgitation at electron-beam CT: Comparison with Doppler echocardiography SO RADIOLOGY LA English DT Article ID LEFT-VENTRICULAR VOLUME; ULTRAFAST COMPUTED-TOMOGRAPHY; FLOW MEASUREMENTS; VALVULAR REGURGITATION; INVIVO VALIDATION; CARDIAC-OUTPUT; HEART-FAILURE; MR; QUANTIFICATION; SEVERITY AB PURPOSE: To prospectively compare mitral valve regurgitation fractions calculated at electron-beam computed tomography (CT) (Doppler echocardiography as reference standard) and to evaluate accuracy of electron-beam CT volume and flow measurements compared with magnetic resonance (MR) imaging results. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Volume and flow measurements were performed at electron-beam CT in 219 patients (197 men, 22 women; mean age, 61.5 years +/- 10.4 [standard deviation]), of whom 157 had known isolated mitral valve regurgitation. Regurgitation volume was calculated as the difference between left ventricular total and forward stroke volumes. Regurgitation fractions were compared with corresponding echocardiographic grades (grades 0-IV) by using Spearman rank correlation and a weighted K test. In 22 patients, CT volume and flow measurements were compared with MR results by using intraclass correlation. RESULTS: Regurgitation fractions at CT correlated well with echocardiographic grading (rank correlation coefficient, r(s) = 0.82; P <.05). Mean regurgitation fractions for echocardiographic grades 0, I, II, III, and IV were 3.1% +/- 6.2, 12.7% +/- 9.9, 25.3% +/- 12.3, 40.4% +/- 11.5, and 55.9% +/- 13.7, respectively. The most suitable thresholds for differentiating echocardiographic grades were calculated regurgitation fractions of 6%, 20%, 30%, and 44%; with these thresholds, individual echocardiographic grades were differentiated (grades 0 vs I-IV, 0-I vs II-IV, 0-II vs III-IV, and 0-III vs IV, respectively) with sensitivities of 89%, 87%, 86%, and 93% and specificities of 81%, 87%, 92%, and 91%, respectively. There was perfect agreement in classification of mitral valve insufficiency between electron-beam CT and echocardiography in 134 (61%) patients and a mismatch by one grade in 72 (33%) and by two grades in 13 (6%) (kappa = 0.84). Intraclass correlation coefficients between CT and MR imaging for total and forward stroke volumes and regurgitation volume and fraction were 0.88, 0.79, 0.93, and 0.89, respectively. CONCLUSION: Electron-beam CT provides quantitative information on severity of mitral valve regurgitation, but semiquantitative classification of regurgitation showed mismatch between electron-beam CT and Doppler echocardiography by at least one grade in more than one-third of all patients. ((c)) RSNA, 2005. C1 Humboldt Univ, Charite Med Sch, Dept Radiol, Berlin, Germany. Humboldt Univ, Charite Med Sch, Dept Internal Med 1, Cardiol Angiol & Pneumol Sect, Berlin, Germany. Humboldt Univ, Charite Med Sch, Dept Cardiovasc Surg, Berlin, Germany. RP Lembcke, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White Bldg 270, Boston, MA 02114 USA. EM alexander.lembcke@gmx.de OI Hermann, Kay-Geert/0000-0001-6142-3814 NR 40 TC 12 Z9 12 U1 0 U2 4 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 JUL PY 2005 VL 236 IS 1 BP 47 EP 55 DI 10.1148/radiol.2361040618 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937DR UT WOS:000229905300007 PM 15987962 ER PT J AU Zalis, ME Perumpillichira, JJ Kim, JY Del Frate, C Magee, C Hahn, PF AF Zalis, ME Perumpillichira, JJ Kim, JY Del Frate, C Magee, C Hahn, PF TI Polyp size at CT colonography after electronic subtraction cleansing in an anthropomorphic colon phantom SO RADIOLOGY LA English DT Article ID COLORECTAL POLYPS; CANCER; SURVEILLANCE; COLONOSCOPY; GUIDELINES AB PURPOSE: To evaluate the effect of various bowel contrast material concentrations and subtraction software on size measurements of well-defined polyp lesions in a colon phantom at CT colonography. MATERIALS AND METHODS: Repeated scanning and a precise reference standard required the use of a colon phantom in which 21 polyps were randomly distributed. Two readers who had each reviewed computed tomographic (CT) colonographic images from more than 100 cases evaluated polyp size on images obtained when the phantom was partially filled with varying concentrations of contrast material, scanned by using CT colonography, and subjected to electronic subtraction cleansing. The single largest dimension was recorded for each reader for a randomized series of polyps. These measurements were compared with a reference standard that was based on a combination of the manufacturer's polyp size specifications and the subsequent verification of these sizes by an independent consensus panel. Six weeks after initial observations, readers evaluated images of the phantom scanned without the presence of contrast material. Polyp size estimations for the two readers for each series were compared with the reference standard to obtain a mean absolute measurement error for each reader for each series. Data for each reader were compared by using a nonparametric Kruskal-Wallis analysis of variance test. A pair-wise comparison of the experimental and control series was then performed by using the Dunn post hoc test. RESULTS: Contrast material dilutions resulting in an average attenuation of less than 500 HU resulted in complete subtraction and the absence of streak artifacts. There was no statistically significant difference between the average measurement error for contrast attenuations between 300 and 500 HU when compared with that of control. Streak artifact was noticeable for the highest dilution (mean, 840 HU). No statistically significant differences were observed for series in which cleansing software was used in the absence of bowel contrast material. CONCLUSION: The combination of electronic cleansing and bowel contrast enhancement in the range of 300-500 HU results in no substantial change in readers' estimations of polyp size at CT colonography. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mzalis@partners.org NR 17 TC 31 Z9 31 U1 0 U2 0 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 JUL PY 2005 VL 236 IS 1 BP 118 EP 124 DI 10.1148/radiol.2361040231 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937DR UT WOS:000229905300015 PM 15987967 ER PT J AU Flampouri, S McNair, HA Donovan, EM Evans, PM Partridge, M Verhaegen, F Nutting, CM AF Flampouri, S McNair, HA Donovan, EM Evans, PM Partridge, M Verhaegen, F Nutting, CM TI Initial patient imaging with an optimised radiotherapy beam for portal imaging SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE portal imaging; low-Z target ID ENERGY BREMSSTRAHLUNG BEAMS; COMPUTED-TOMOGRAPHY; LINEAR-ACCELERATOR; MEGAVOLTAGE CT; SYSTEM; THERAPY; SCREENS; IMAGES; TARGET AB Background and purpose: To investigate the feasibility and the advantages of a portal-imaging mode on a medical accelerator, consisting of a thin low-Z bremsstrahlung target and a thin Gd2O2S/film detector, for patient imaging. Patients and methods: The international code of practice for high-energy photon dosimetry was used to calibrate dosimetry instruments for the imaging beam produced by 4.75 MeV electrons hitting a 6 mm thick aluminium target. Images of the head and neck of a humanoid phantom were taken with a mammography film system and the dose in the phantom was measured with TLDs calibrated for this beam. The first head and neck patient images are compared with conventional images (taken with the treatment beam on a film radiotherapy verification detector). Visibility of structures for six patients was evaluated. Results: Images of the head and neck of a humanoid phantom, taken with both imaging systems showed that the contrast increased dramatically for the new system while the dose required to form an image was less than 10(-2) Gy. The patient images taken with the new and the conventional systems showed that air-tissue interfaces were better defined in the new system image. Anatomical structures, visible on both films, are clearer with the new system. Additionally, bony structures, such as vertebrae, were clearly visible only with the new system. The system under evaluation was significantly better for all features in lateral images and most features in anterior images. Conclusions: This pilot study of the new portal imaging system showed the image quality is significantly improved. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Inst Canc Res, Joint Phys Dept, Sutton SM2 5PT, Surrey, England. Royal Marsden NHS Trust, Joint Phys Dept, Sutton SM2 5PT, Surrey, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Royal Marsden NHS Trust, Dept Radiotherapy, Sutton, Surrey, England. McGill Univ, Dept Med Phys, Montreal, PQ, Canada. Royal Marsden NHS Trust, Head & Neck Unit, London, England. Inst Canc Res, London SW3 6JB, England. RP Evans, PM (reprint author), Inst Canc Res, Joint Phys Dept, Downs Rd, Sutton SM2 5PT, Surrey, England. EM phil.evans@icr.ac.uk RI Evans, Philip/A-6257-2009; OI Donovan, Ellen/0000-0003-1692-1587; Partridge, Mike/0000-0002-8876-8190 NR 20 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JUL PY 2005 VL 76 IS 1 BP 63 EP 71 DI 10.1016/j.radonc.2005.04.006 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 957ZD UT WOS:000231411200011 PM 15919125 ER PT J AU Rae, A Jackson, D Ramanan, P Flanz, J Leyman, D AF Rae, A Jackson, D Ramanan, P Flanz, J Leyman, D TI Critical feature analysis of a radiotherapy machine SO RELIABILITY ENGINEERING & SYSTEM SAFETY LA English DT Article; Proceedings Paper CT 22nd International Conference on Computer Safety, Reliability and Security CY SEP 23-26, 2003 CL EDINBURGH, SCOTLAND SP British Comp Soc, DIRC, European Asoc Cognit Ergon, ENCRESS, Gesell Informatik, IEE, Int Federat Automat Control, IFIG WG10 4, IFIG WG13 5, ISA EUNET, Austrian Comp Soc, Safety Critical Syst Club, Software Reliabil & Metr Club AB The software implementation of the emergency shutdown feature in a major radiotherapy system was analyzed, using a directed form of code review based on module dependences. Dependences between modules are labelled by particular assumptions; this allows one to trace through the code, and identify those fragments responsible for critical features. An 'assumption tree' is constructed in parallel, showing the assumptions which each module makes about others. The root of the assumption tree is the critical feature of interest, and its leaves represent assumptions which, if not valid, might cause the critical feature to fail. The analysis revealed some unexpected assumptions that motivated improvements to the code. (c) 2004 Elsevier Ltd. All rights reserved. C1 MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Univ Queensland, St Lucia, Qld, Australia. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Ion Beam Applicat, Louvain, Belgium. RP Rae, A (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 32 Vassar St 32 G704, Cambridge, MA 02139 USA. EM arae@itee.uq.edu.au; dnj@mit.edu; flanz@hadron.mgh.harvard.edu; leyman@iba.be RI Rae, Andrew/K-2908-2016 OI Rae, Andrew/0000-0002-9540-503X NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0951-8320 J9 RELIAB ENG SYST SAFE JI Reliab. Eng. Syst. Saf. PD JUL PY 2005 VL 89 IS 1 BP 48 EP 56 DI 10.1016/j.ress.2004.08.006 PG 9 WC Engineering, Industrial; Operations Research & Management Science SC Engineering; Operations Research & Management Science GA 913MP UT WOS:000228156200005 ER PT J AU Arroyo, JG Bula, D AF Arroyo, JG Bula, D TI Congenital hypertrophy of the retinal pigment epithelium inhibits drusen formation SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Editorial Material DE congenital; hypertrophy; retinal pigment; epithelium; drusen; formation ID MACULAR DEGENERATION C1 Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Div Ophthalmol, Retina Serv, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Div Ophthalmol, Retina Serv, 330 Brookline Ave,Shapiro 5th Floor, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUL-AUG PY 2005 VL 25 IS 5 BP 669 EP 671 DI 10.1097/00006982-200507000-00023 PG 3 WC Ophthalmology SC Ophthalmology GA 008AO UT WOS:000235012800023 PM 16077370 ER PT J AU Bolay, H Moskowitz, MA AF Bolay, H Moskowitz, MA TI The emerging importance of cortical spreading depression in migraine headache SO REVUE NEUROLOGIQUE LA English DT Article DE migraine aura; cortical spreading depression; trigeminovascular activation; matrix metalloproteinases; nitric oxide ID CORTEX; PAIN AB Migraine is a disabling neurovascular disorder with a complex pathophysiology. Functional imaging and magneto encephalographic studies strongly suggest that Cortical Spreading Depression (CSD) constitutes the biological basis for the neurologic aura that precedes headache in one fourth of migrainers. It is likely that the aura is the generator of the headache since experimentally, CSD triggers the activation of the trigeminovascular system, possibly through matrix metalloproteases activation which is associated with an increase in vascular permeability. These data may have therapeutic implications: strategies to block trigeminal activation or its downstream consequences are central to treat the acute headache whereas strategies to block events lying upstream of trigeminal activation would be crucial in prophylaxis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Gazi Univ Hosp, Dept Neurol, Ankara, Turkey. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Stroke & Neurovasc Regulat Lab, Room 6403,149 13th St, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 7 TC 25 Z9 25 U1 2 U2 3 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0035-3787 J9 REV NEUROL-FRANCE JI Rev. Neurol. PD JUL PY 2005 VL 161 IS 6-7 BP 655 EP 657 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 943HU UT WOS:000230344900006 PM 16141950 ER PT J AU Lembcke, A Dohmen, PM Wiese, TH Kivelitz, DE Rogalla, P Dewey, M Klessen, C Hamm, B Konertz, WF Enzweiler, CNH AF Lembcke, A Dohmen, PM Wiese, TH Kivelitz, DE Rogalla, P Dewey, M Klessen, C Hamm, B Konertz, WF Enzweiler, CNH TI Surgery of congestive heart failure - The role of computed tomography in the pre- and postsurgical diagnostic evaluation SO ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN LA German DT Review DE computed tomography (CT); heart, failure; heart, function; heart, surgery; heart, transplantation ID PARTIAL LEFT VENTRICULECTOMY; ELECTRON-BEAM TOMOGRAPHY; CORONARY-ARTERY-DISEASE; MULTIDETECTOR ROW CT; MITRAL-VALVE REGURGITATION; MULTISLICE SPIRAL CT; EJECTION FRACTION; BYPASS GRAFTS; DYNAMIC CARDIOMYOPLASTY; DILATED CARDIOMYOPATHY AB The treatment of advanced, drug resistant congestive heart failure gains in importance in the field of cardiac surgery. Cardiac imaging for preoperative assessment and follow-up focuses on the determination of ventricular volumes and function as well as on the detection of postoperative complications. Computed tomography (CT) is highly accurate irrespective of the individual patient's anatomic situation, has a low examiner dependence and short examination time, does not require an arterial vascular access and can be performed in patients with metal implants. CT is the modality of choice in the follow-up of heart transplants to detect extracardiac and cardiac complications including coronary calcifications as an early sign of transplant vasculopathy. In addition, CT visualizes the elements of mechanical assist devices and can identify their possible local cardiac and mediastinal complications. CT can detect fibrolipomatous involution of the mobilized muscle flap in dynamic cardiomyoplasty and can depict fibrous reactions along the epicardial mesh implant in passive cardiac containment. Further indications include assessment of typical local postoperative complications, such as intrathoracic infection and mediastinal bleeding, intracardiac thrombus formation or pericardial effusion. CT is routinely used for evaluating bypass patency but is limited in assessing associated valve defects since it does not visualize flow. C1 Univ Med Berlin, Inst Radiol, Charite, Berlin, Germany. Univ Med Berlin, Klin Kardiovaskulare Chirurg, Charite, Berlin, Germany. Augusta Kranken Anstalt, Inst Radiol, Bochum, Germany. RP Lembcke, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit White Bldg,Room 270, Boston, MA 02114 USA. EM Alexander.Lembcke@gmx.de NR 57 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 1438-9029 J9 ROFO-FORTSCHR RONTG JI Rofo-Fortschr. Gebiet Rontgenstrahlen Bildgeb. Verfahr. PD JUL PY 2005 VL 177 IS 7 BP 946 EP 954 DI 10.1055/s-2005-857960 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 942HQ UT WOS:000230273900004 PM 15973596 ER PT J AU von Boehmer, H AF von Boehmer, H TI Peptide-based instruction of suppressor commitment in naive T cells and dynamics of immunosuppression in vivo SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Review ID IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; GENERATED EX-VIVO; DENDRITIC CELLS; TGF-BETA; PERIPHERAL TOLERANCE; AUTOIMMUNE-DISEASES; REGULATORY CELLS; ORAL TOLERANCE; STEADY-STATE AB Recent years have witnessed the revival of suppressor T cells that control immunity by interfering with the generation of effector T-cell function in vivo. The discovery that CD4 T cells with the CD25 surface marker were enriched in suppressor activity enabled further phenotypic and functional analysis of the so-called natural suppressor cells. In vitro characterization showed that these cells were anergic, i.e. did not respond to antigenic stimulation with proliferation and, instead they suppressed other cells through direct cell contact resulting in inhibition of interleukin-2 gene transcription. We have analysed the generation and function of suppressor T cells in T-cell receptor (TCR) transgenic mice. The results showed that such cells can be generated intrathymically when agonist TCR ligands are expressed on thymic epithelial cells. Thus generated cells constitute a lineage of cells committed to suppression only with the ability to survive for prolonged periods of time in the absence of the inducing ligand. Because of appropriate homing receptors such cells can accumulate and proliferate in antigen draining lymphnodes after antigenic stimulation and suppress proliferation and cytokine secretion of CD4 and CD8 T cells as well as CD8 T-cell-mediated cytotoxicity. We also attempted to generate such cells from naive T cells in secondary lymphoid tissue under conditions where expansion of already preformed suppressor T cells could be excluded. The results showed that subimmunogenic peptide delivery by osmotic minipumps or by peptide containing DEC 205 antibodies yielded CD25(+) suppressor cells that were phenotypically and functionally indistinguishable from intrathymically generated suppressor cells. The experiments with DEC205 antibodies revealed (i) dose-dependent proliferation of naive T cells and (ii)- conversion into suppressor T cells of only those T cells that underwent a limited number of cell divisions. These results are compatible with other studies that were, however, less rigorous in excluding expansion of existing cells as opposed to de novo generation of suppressor cells from naive T cells. The fact that natural suppressor cells have an essential role in preventing autoimmunity and that they can be specifically induced by TCR agonist ligands opens new perspectives in preventing autoimmunity, transplant rejection and allergy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 49 TC 11 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUL PY 2005 VL 62 SU 1 BP 49 EP 54 DI 10.1111/j.1365-3083.2005.01609.x PG 6 WC Immunology SC Immunology GA 951XK UT WOS:000230965500011 PM 15953184 ER PT J AU Koike, K Hashimoto, K Takai, N Shimizu, E Komatsu, N Watanabe, H Nakazato, M Okamura, N Stevens, KE Freedman, R Iyo, M AF Koike, K Hashimoto, K Takai, N Shimizu, E Komatsu, N Watanabe, H Nakazato, M Okamura, N Stevens, KE Freedman, R Iyo, M TI Tropisetron improves deficits in auditory P50 suppression in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE nicotinic receptors; serotonin receptors; evoked potentials auditory; schizophrenia; tropisetron; drug therapy ID ACETYLCHOLINE-RELEASE; NICOTINIC RECEPTORS; CIGARETTE-SMOKING; CORTEX; BRAIN; NORMALIZATION; RELATIVES AB Physiological deficits in inhibition of the P50 auditory evoked potential in schizophrenia have been related to diminished expression of alpha 7 nicotinic acetylcholine receptors. Diminished P50 inhibition is correlated with neuropsychological deficits in attention, one of the principal neurocognitive disturbances in schizophrenia. Nicotine administration improves P50 inhibition, presumably by achieving additional activation of these diminished receptors, but its toxicity and marked tachyphytaxis make it an ineffective therapeutic. Nicotine also has weak positive effects on several neurocognitive deficits in schizophrenia, which raises the possibility that the alpha 7 nicotinic receptor is a clinically relevant therapeutic target that should be addressed by less toxic agents. Tropisetron, a drug already approved for clinical use outside the United States as an anti-emetic, is a partial agonist at a7 nicotinic receptors and an antagonist at 5-HT3 receptors. As an initial proof-of-principle study, we determined that a single administration of tropisetron significantly improves P50 inhibition in schizophrenia. These data are consistent with biological activity at a pathophysiological mechanism in schizophrenia and support further trials of this drug as a possible therapeutic for neurocognitive deficits in schizophrenia. (c) 2005 Elsevier B.V. All rights reserved. C1 Chiba Univ, Grad Sch Med, Dept Psychiat, Chiba 2608670, Japan. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Hashimoto, K (reprint author), Chiba Univ, Grad Sch Med, Dept Psychiat, 1-8-1 Inohana, Chiba 2608670, Japan. EM hashimoto@faculty.chiba-u.jp FU NIMH NIH HHS [MH-59565, MH-68582] NR 34 TC 96 Z9 100 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 1 PY 2005 VL 76 IS 1 BP 67 EP 72 DI 10.1016/j.schres.2004.12.016 PG 6 WC Psychiatry SC Psychiatry GA 937AR UT WOS:000229897400005 PM 15927799 ER PT J AU Andress, DL AF Andress, DL TI Vitamin D in health and disease - Introduction SO SEMINARS IN DIALYSIS LA English DT Editorial Material C1 Univ Washington, Sch Med, Nephrol Sect, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Andress, DL (reprint author), Univ Washington, Sch Med, Nephrol Sect, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 2005 VL 18 IS 4 BP 265 EP 265 DI 10.1111/j.1525-139X.2005.18401.x PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 945HG UT WOS:000230493000001 ER PT J AU Wolf, M Thadhani, R AF Wolf, M Thadhani, R TI Beyond minerals and parathyroid hormone: Role of active vitamin D in end-stage renal disease SO SEMINARS IN DIALYSIS LA English DT Article ID D-RECEPTOR LIGANDS; 1,25-DIHYDROXYVITAMIN D-3; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; 19-NOR-1,25-DIHYDROXYVITAMIN D-2; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; AUTOIMMUNE-DISEASES; CELL-PROLIFERATION; DIALYSIS PATIENTS AB Secondary hyperparathyroidism is a common complication of end-stage renal disease (ESRD) that is often treated with activated forms of intravenous vitamin D. The natural course and treatment of secondary hyperparathyroidism in hemodialysis patients is punctuated by episodes of hypercalcemia, hyperphosphatemia, and increased calcium-phosphate product, which in previous studies were linked to increased mortality. Historically these episodes have been attributed to vitamin D, leading some authorities to favor decreased vitamin D use. However, the studies that examined the impact of mineral levels and parathyroid hormone (PTH) on survival did not consistently account for vitamin D therapy itself on hemodialysis patient survival. The current review examines in detail two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol and a second that demonstrated a significant survival advantage of any intravenous vitamin D formulation versus none. In both studies, the effects were independent of mineral and PTH levels, suggesting "nontraditional" actions of vitamin D contributed to the observed survival advantage. Several of these nontraditional actions are reviewed with an emphasis on those that might impact hemodialysis outcomes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bartlett 911,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org NR 73 TC 19 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 2005 VL 18 IS 4 BP 302 EP 306 DI 10.1111/j.1525-139X.2005.18406.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 945HG UT WOS:000230493000007 PM 16076353 ER PT J AU Andress, DL AF Andress, DL TI Vitamin D treatment in chronic kidney disease SO SEMINARS IN DIALYSIS LA English DT Article ID CHRONIC-RENAL-FAILURE; SERUM PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; 1,25-DIHYDROXYVITAMIN D-3; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; 1-ALPHA-HYDROXYVITAMIN D-2; CARDIOVASCULAR-DISEASE; INTRAVENOUS CALCITRIOL; NEPHRECTOMIZED RATS AB Activated vitamin D continues to be the major treatment for suppressing parathyroid hormone (PTH) levels in dialysis patients who have secondary hyperparathyroidism. Active vitamin D compounds are distinguished by their ability to bind with high affinity to vitamin D receptors (VDRs) not only in the parathyroid glands, but in cells throughout the body. Because of recent data showing that pulsatile, intravenous vitamin D treatment (calcitriol or paricalcitol) confers a survival advantage in the dialysis population, there is new interest in understanding the systemic effects of VDR activation, particularly in the predialysis stages of chronic kidney disease (CKD), where high mortality rates from cardiovascular disease have recently been documented. Previous underutilization of calcitriol treatment to control PTH levels in stages 3 and 4 CKD was often due to concerns about its potential for accelerating the progression of CKD as a consequence of hypercalcemia, hypercalciuria, or hyperphosphatemia. Vitamin D analogs with selective VDR activity (such as paricalcitol) have great potential for preventing parathyroid hyperplasia and bone loss in early CKD without adversely affecting kidney function. Whether they also reduce cardiovascular morbidity and mortality in early CKD, as they appear to do in dialysis patients, remains to be determined. C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Andress, DL (reprint author), Vet Affairs Med Ctr, Mailstop 111A,1660 S Columbian Way, Seattle, WA 98108 USA. EM Dennis.Andress@med.va.gov NR 83 TC 39 Z9 43 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 2005 VL 18 IS 4 BP 315 EP 321 DI 10.1111/j.1525-139X.2005.18408.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 945HG UT WOS:000230493000009 PM 16076355 ER PT J AU Chang, VW Christakis, NA AF Chang, VW Christakis, NA TI Income inequality and weight status in US metropolitan areas SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE income inequality; obesity; body mass index; contextual analysis; socioeconomic factors; USA ID SELF-RATED HEALTH; BODY-MASS INDEX; UNITED-STATES; POPULATION HEALTH; MULTILEVEL ANALYSIS; INDIVIDUAL INCOME; YOUNG ADULTHOOD; LIFE EXPECTANCY; NATIONAL SURVEY; MORTALITY AB Prior empirical studies have demonstrated an association between income inequality and general health endpoints such as mortality and self-rated health, and findings have been taken as support for the hypothesis that inequality is detrimental to individual health. Unhealthy weight statuses may function as an intermediary link between inequality and more general heath endpoints. Using individual-level data from the 1996-98 Behavioral Risk Factor Surveillance System, we examine the relationship between individual weight status and income inequality in US metropolitan areas. Income inequality is calculated with data from the 1990 US Census 5% Public Use Microsample. In analyses stratified by race-sex groups, we do not find a positive association between income inequality and weight outcomes such as body mass index, the odds of being overweight, and the odds of being obese. Among white women, however, we do find a statistically significant inverse association between inequality and each of these weight outcomes, despite adjustments for individual-level covariates, metropolitan-level covariates, and census region. We also find that greater inequality is associated with higher odds for trying to lose weight among white women, even adjusting for current weight status. Although our findings are suggestive of a contextual effect of metropolitan area income inequality, we do not find an increased risk for unhealthy weight outcomes, adding to recent debates surrounding this topic. © 2004 Elsevier Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Univ Penn, Populat Studies Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. RP Chang, VW (reprint author), Univ Penn, Sch Med, Dept Med, 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vwchang@mail.med.upenn.edu RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU NICHD NIH HHS [5-K12-HD043459] NR 68 TC 31 Z9 31 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUL PY 2005 VL 61 IS 1 BP 83 EP 96 DI 10.1016/j.socscimed.2004.11.036 PG 14 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 923CY UT WOS:000228887800008 PM 15847964 ER PT J AU Garshick, E Kelley, A Cohen, S Garrison, A Tun, CG Gagnon, D Brown, R AF Garshick, E Kelley, A Cohen, S Garrison, A Tun, CG Gagnon, D Brown, R TI A prospective assessment of mortality in chronic spinal cord injury SO SPINAL CORD LA English DT Article; Proceedings Paper CT Spinal Cord Conference and Training CY JUN, 2003 CL Long Beach, CA DE spinal cord injury (SCI); mortality; heart diseases; diabetes; smoking ID LONG-TERM SURVIVAL; HEART-DISEASE; HEALTH; POPULATION; STANDARDS; SYMPTOMS; ADULTS; DEATH; LUNG; AGE AB Study design: Prospective mortality study. Objective: To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI). Setting: Boston, MA, USA. Methods: Between 1994 and 2000, 361 males >= 1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33-74.4 months) through 12/31/2000 using the National Death Index. Results: At entry, mean (+/- SD) age was 50.6 +/- 15.0 years (range 23-87) and years since injury was 17.5 +/- 12.8 years (range 1.0-56.5). Mortality was elevated (observed/expected deaths 37/25.1; SMR 1.47; 95% CI = 1.04-2.03) compared to US rates. Risk factors for death were diabetes (RR = 2.62; 95% CI 1.19-5.77), heart disease (RR = 3.66; 95% CI 1.77-7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390-459) in 40%, and of the respiratory system in 24% (ICD-9 460-519). Conclusions: These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Channing Lab,VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02118 USA. VA Boston Healthcare Syst, Rehabil Med Serv, Boston, MA USA. Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. OI Gagnon, David/0000-0002-6367-3179 FU NICHD NIH HHS [R01 HD042141, R01 HD42141] NR 35 TC 245 Z9 253 U1 4 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUL PY 2005 VL 43 IS 7 BP 408 EP 416 DI 10.1038/sj.sc.3101729 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 941WJ UT WOS:000230244600004 PM 15711609 ER PT J AU King, D Chase, J Havey, RM Voronov, L Sartori, M McEwen, HA Beamer, WG Patwardhan, AG AF King, D Chase, J Havey, RM Voronov, L Sartori, M McEwen, HA Beamer, WG Patwardhan, AG TI Effects of growth hormone transgene expression on vertebrae in a mouse model of osteogenesis imperfecta SO SPINE LA English DT Article DE osteogenesis imperfecta; oim; transgenic; growth hormone; biomechanics ID COLLAGEN-SYNTHESIS; MICE; OIM; MORPHOLOGY AB Study Design. A human growth hormone transgene was bred into mice of the Cola2(oim) (oim) lineage. Caudal ( tail) vertebrae from male and female mice at early skeletal maturity and at midlife were evaluated for physical and biomechanical properties. Objective. To test whether constant low-level growth hormone expression within the marrow could improve structural or material properties of caudal vertebrae in oim mice. Summary of Background Data. A spontaneous genetic defect in a type I procollagen gene created the oim mouse model for osteogenesis imperfecta. Bones of heterozygous oim mice are biomechanically inferior to wild-type controls. Bone marrow expression of human growth hormone was demonstrated previously to enhance bone deposition and structural biomechanical properties in caudal vertebrae of transgenic mice. Methods. Compression tests were performed individually on three caudal vertebrae (Ca4, 5, and 6) from each mouse to determine their structural biomechanical properties. Volumetric and mineral content measurements were also made. In a subset of vertebrae, the ashing measurements were confirmed and extended by peripheral quantitative tomographic scanning, which also allowed calculation of the failure stress. Results. Heterozygous oim mouse vertebrae had structural and material properties inferior to the wild-type controls. Growth hormone transgene expression increased the size and mineral content of the vertebrae from mutant mice, and increased biomechanical structural values for maximum load and energy to failure. Failure stress was not improved. Conclusions. Growth hormone stimulation of size and bone mineral content of osteogenesis imperfecta mutant mouse caudal vertebrae contributed to their improved performance in axial compression. There was no evidence for improved material properties, however. C1 Northeastern Ohio Univ Coll Med & Pharm, Dept Biochem & Mol Pathol, Coll Med, Rootstown, OH 44272 USA. Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Musculoskeletal Biomech Lab, Hines, IL 60141 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP King, D (reprint author), Northeastern Ohio Univ Coll Med & Pharm, Dept Biochem & Mol Pathol, Coll Med, 4209 State Route 44, Rootstown, OH 44272 USA. EM dk@neoucom.edu RI McEwen, Heather/B-2314-2008 OI McEwen, Heather/0000-0001-7922-192X FU NIAMS NIH HHS [AR43618] NR 17 TC 7 Z9 8 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUL 1 PY 2005 VL 30 IS 13 BP 1491 EP 1495 DI 10.1097/01.brs.0000168550.65726.cb PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 943EN UT WOS:000230335300004 PM 15990661 ER PT J AU Jarvik, JG Hollingworth, W Heagerty, PJ Haynor, DR Boyko, EJ Deyo, RA AF Jarvik, JG Hollingworth, W Heagerty, PJ Haynor, DR Boyko, EJ Deyo, RA TI Three-year incidence of low back pain in an initially asymptomatic cohort - Clinical and imaging risk factors SO SPINE LA English DT Article DE cohort study; epidemiology; low back pain; prognosis; risk factors; magnetic resonance imaging ID DEGENERATIVE DISK DISEASE; MAGNETIC-RESONANCE; LUMBAR SPINE; PSYCHOSOCIAL FACTORS; PREVALENCE; PROTRUSIONS; DISABILITY; INTENSITY; SCIATICA; TEARS AB Study Design. Prospective cohort study of randomly selected Veterans Affairs out-patients without baseline low back pain (LBP). Objective. To determine predictors of new LBP as well as the 3-year incidence of magnetic resonance imaging (MRI) findings. Summary of Background Data. Few prospective studies have examined clinical and anatomic risk factors for the development of LBP, or the incidence of new imaging findings and their relationship to back pain onset. Methods. We randomly selected 148 Veterans Affairs out-patients (aged 35 to 70) without LBP in the past 4 months. We compared baseline and 3-year lumbar spine MRI. Using data collected every 4 months, we developed a prediction model of back pain-free survival. Results. After 3 years, 131 subjects were contacted, and 123 had repeat MRI. The 3-year incidence of pain was 67% ( 88 of 131). Depression had the largest hazard ratio (2.3, 95% CI = 1.2-4.4) of any baseline predictor of incident back pain. Among baseline imaging findings, central spinal stenosis and nerve root contact had the highest, though nonsignificant, hazard ratios. We did not find an association between new LBP and type 1 end-plate changes, disc degeneration, annular tears, or facet degeneration. The incidence of new MRI findings was low, with the most common new finding being disc signal loss in 11 (9%) subjects. All five subjects with new disc extrusions and all four subjects with new nerve root impingement had new pain. Conclusion. Depression is an important predictor of new LBP, with MRI findings likely less important. New imaging findings have a low incidence; disc extrusions and nerve root contact may be the most important of these findings. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Jarvik, JG (reprint author), Univ Washington, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM jarvikj@u.washington.edu FU AHRQ HHS [HS-08194, HS-094990]; NIAMS NIH HHS [P60-AR48093-01] NR 30 TC 115 Z9 123 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUL 1 PY 2005 VL 30 IS 13 BP 1541 EP 1548 DI 10.1097/01.brs.0000167536.60002.87 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 943EN UT WOS:000230335300013 PM 15990670 ER PT J AU Daffertshofer, M Gass, A Ringleb, P Sitzer, M Sliwka, U Els, T Sedlaczek, O Koroshetz, WJ Hennerici, MG AF Daffertshofer, M Gass, A Ringleb, P Sitzer, M Sliwka, U Els, T Sedlaczek, O Koroshetz, WJ Hennerici, MG TI Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia - Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator - Results of a phase II clinical trial SO STROKE LA English DT Article DE stroke, acute; thrombolysis; ultrasonography ID CEREBRAL-ARTERY OCCLUSION; ACUTE STROKE; IN-VITRO; RECANALIZATION; MODEL; CRANIUM; FLOW; MRI AB Background - Clinical studies using ultrasound at diagnostic frequencies in transcranial Doppler devices provided encouraging results in enhancing thrombolysis with tissue plasminogen activator (tPA) in acute stroke. Low-frequency ultrasound does not require complex positioning procedures, penetrates through the skull better, and has been demonstrated to accelerate thrombolysis with tPA in animal experiments in wide cerebrovascular territories without hemorrhagic side effects. We therefore conducted the first multicenter clinical trial to investigate safety of tPA plus low-frequency ultrasound (300 kHz). Methods - Acute stroke patients within a 6-hour time window were included (National Institutes of Health Stroke Scale scores > 4). Magnetic resonance imaging (MRI) was used to document vascular occlusion and to rule out cerebral hemorrhage. Patients were allocated to combination therapy alternately; the first patient received tPA only, the second patient received tPA plus ultrasound, etc. Follow-up included serial MRI directly thereafter and 24 hours later to confirm recanalization and tissue imaging. Clinical recovery was measured after treatment and 3 months later. Results - 26 patients (70.4 +/- 9.7 years) entered the trial (12 tPA, 14 tPA plus ultrasound). The study was prematurely stopped because 5 of 12 patients from the tPA only group but 13 of 14 patients treated with the tPA plus ultrasound showed signs of bleeding in MRI (P < 0.01). Within 3 days of treatment, 5 symptomatic hemorrhages occurred within the tPA plus ultrasound group. At 3 months, neither morbidity nor treatment- related mortality or recanalization rates differed between both groups. Conclusions - This study demonstrated bioeffects from low-frequency ultrasound that caused an increased rate of cerebral hemorrhages in patients concomitantly treated with intravenous tPA. C1 Univ Heidelberg, Dept Neurol, Klinikum Mannheim, D-69135 Mannheim, Germany. Univ Basel Hosp, CH-4031 Basel, Switzerland. Univ Hamburg, Dept Neurol, Hamburg, Germany. Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Daffertshofer, M (reprint author), Univ Heidelberg, Dept Neurol, Klinikum Mannheim, Theodor Kutzer Ufer 1-3, D-69135 Mannheim, Germany. EM daffertshofer@neuro.ma.uni-heidelberg.de OI Ringleb, Peter/0000-0002-5473-8671 NR 24 TC 224 Z9 234 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2005 VL 36 IS 7 BP 1441 EP 1446 DI 10.1161/01.STR.0000170707.86793.1a PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 941BW UT WOS:000230190600023 PM 15947262 ER PT J AU Bravata, DM Wells, CK Gulanski, B Kernan, WN Brass, LM Long, J Concato, J AF Bravata, DM Wells, CK Gulanski, B Kernan, WN Brass, LM Long, J Concato, J TI Racial disparities in stroke risk factors - The impact of socioeconomic status SO STROKE LA English DT Article DE ischemia; risk factors; social class ID ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; ISCHEMIC-STROKE; SOCIAL-CLASS; MORTALITY; REGISTER; BLACKS; RACE; ATHEROSCLEROSIS; ENDARTERECTOMY AB Background and Purpose - In the US, blacks have a higher incidence of stroke and more severe strokes than whites. Our objective was to determine if differences in income, education, and insurance, as well as differences in the prevalence of stroke risk factors, accounted for the association between ethnicity and stroke. Methods - We used data from the Third National Health and Nutrition Survey (NHANES III), a cross-sectional sample of the noninstitutionalized US population (1988 - 1994), and included blacks and whites aged 40 years or older with a self-reported stroke history. Income was assessed using a ratio of income to US Census Bureau annual poverty threshold. Results - Among 11 163 participants, 2752 (25 %) were black and 619 (6 %) had a stroke history (blacks: 160/ 2752 [6 %]; whites: 459/8411 [6 %]; P = 0.48). Blacks had a higher prevalence of 5 risk factors independently associated with stroke: hypertension, treated diabetes, claudication, higher C-reactive protein, and inactivity; whites had a higher prevalence of 3 risk factors: older age, myocardial infarction, and lower high-density lipoprotein cholesterol. Ethnicity was independently associated with stroke after adjusting for the 8 risk factors ( adjusted odds ratio, 1.32; 95 % CI, 1.04 to 1.67). Ethnicity was not independently associated with stroke after adjustment for income and income was independently associated with stroke (adjusted odds ratios for: ethnicity, 1.15; 95 % CI, 0.88 to 1.49; income, 0.89; 95 % CI, 0.82 to 0.95). Adjustment for neither education nor insurance altered the ethnicity - stroke association. Conclusions - In this study of community-dwelling stroke survivors, ethnic differences exist in the prevalence of stroke risk factors and income may explain the association between ethnicity and stroke. C1 W Haven VA Med Ctr, VA Connecticut Healthcare Syst, CERC, West Haven, CT 06516 USA. VA Connecticut Healthcare Syst, Internal Med Serv, West Haven, CT 06516 USA. VA Connecticut Healthcare Syst, Neurol Serv, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Dept Internal Med, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Bravata, DM (reprint author), W Haven VA Med Ctr, VA Connecticut Healthcare Syst, CERC, Bldg 35A,Mailcode 151B,950 Campbell Ave, West Haven, CT 06516 USA. EM Dawn.Bravata@yale.edu NR 30 TC 56 Z9 58 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2005 VL 36 IS 7 BP 1507 EP 1511 DI 10.1161/01.STR.0000170991.63594.b6 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 941BW UT WOS:000230190600035 PM 15961710 ER PT J AU Cronin, S Furie, KL Kelly, PJ AF Cronin, S Furie, KL Kelly, PJ TI Dose-related association of MTHFR 677T allele with risk of ischemic stroke - Evidence from a cumulative meta-analysis SO STROKE LA English DT Article DE cerebrovascular disorders; folic acid; gene mutation; homocysteine ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FACTOR-V-LEIDEN; INHERITED PROTHROMBOTIC CONDITIONS; ELEVATED PLASMA HOMOCYSTEINE; CERVICAL ARTERY DISSECTION; HOMOZYGOUS C677T MUTATION; YOUNG-ADULTS; CEREBROVASCULAR-DISEASE; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; VASCULAR DEMENTIA AB Background - Data are conflicting concerning ischemic stroke risk associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C -> T), which predisposes to hyperhomocystinemia in vivo. Methods - We performed a systematic review and meta-analysis of published relevant literature. We included cohort, case-control, or cross-sectional studies reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best-phenotyped group). Results - Among 14 870 subjects, the pooled estimated risk of stroke/TIA associated with the 677T allele increased in a dose-dependent manner (T allele pooled OR 1.17, 95 % CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95 % CI 1.15 to 1.64). An almost-identical relationship was observed when the analysis was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95 % CI 1.09 to 1.29, TT genotype pooled OR 1.48, 95 % CI 1.22 to 1.8). Conclusion - A graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose was observed, suggesting an influence of this polymorphism as a genetic stroke risk factor and supporting other evidence indicating a causal relationship between elevated homocysteine and stroke. C1 Mater Misericordiae Univ Hosp, Neurovasc Clin Sci Unit, Dublin 7, Ireland. Mater Misericordiae Univ Hosp, Dept Neurol, Dublin 7, Ireland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Mater Misericordiae Univ Hosp, Neurovasc Clin Sci Unit, Eccles St, Dublin 7, Ireland. EM pjkelly@partners.org FU NCRR NIH HHS [M01-RR-01066]; NINDS NIH HHS [K23 NS42720] NR 65 TC 112 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 JUL PY 2005 VL 36 IS 7 BP 1581 EP 1587 DI 10.1161/01.STR.0000169946.31639.af PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 941BW UT WOS:000230190600050 PM 15947278 ER PT J AU Alberts, MJ Latchaw, RE Selman, WR Shephard, T Hadley, MN Brass, LM Koroshetz, W Marler, JR Booss, J Zorowitz, RD Croft, JB Magnis, E Mulligan, D Jagoda, A O'Connor, R Cawley, CM Connors, JJ Rose-DeRenzy, JA Emr, M Warren, M Walker, MD AF Alberts, MJ Latchaw, RE Selman, WR Shephard, T Hadley, MN Brass, LM Koroshetz, W Marler, JR Booss, J Zorowitz, RD Croft, JB Magnis, E Mulligan, D Jagoda, A O'Connor, R Cawley, CM Connors, JJ Rose-DeRenzy, JA Emr, M Warren, M Walker, MD CA Brain Attack Coalition TI Recommendations for comprehensive stroke centers - A consensus statement from the brain attack coalition SO STROKE LA English DT Review DE cerebrovascular disorders; cerebral hemorrhage; healthcare systems; patient care; university medical centers ID AMERICAN-HEART-ASSOCIATION; DIGITAL-SUBTRACTION-ANGIOGRAPHY; CAROTID-ARTERY STENOSIS; MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC-STROKE; HEALTH-CARE PROFESSIONALS; ANEURYSMAL SUBARACHNOID HEMORRHAGE; MAGNETIC-RESONANCE ANGIOGRAPHY; DURAL SINUS THROMBOSIS; SPECIAL WRITING GROUP AB Background and Purpose - To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. Summary of Review - A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. Conclusions - There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center. C1 Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. Univ Hosp Cleveland, Dept Neurosurg, Cleveland, OH 44106 USA. Neurosci Consultants, Richmond, VA USA. Univ Alabama, Dept Neurosurg, Birmingham, AL USA. VA Connecticut Healthcare Syst, Neurol Serv, New Haven, CT USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NINDS, Bethesda, MD 20892 USA. Dept Vet Affairs, Off Natl Director Neurol, West Haven, CT USA. Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. Miami Cardiac & Vasc Inst, Miami, FL USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Amer Stroke Assoc, Dallas, TX USA. Natl Stroke Assoc, Englewood, CO USA. Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. Christiana Care Hlth Syst, Newark, DE USA. Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA. OSF St Francis Med Ctr, Peoria, IL USA. RP Alberts, MJ (reprint author), Northwestern Univ, Sch Med, Stroke Program, 710 N Lake Shore Dr,Room 1420, Chicago, IL 60611 USA. EM m-alberts@northwestern.edu OI Zorowitz, Richard/0000-0001-8938-786X NR 268 TC 316 Z9 327 U1 3 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2005 VL 36 IS 7 BP 1597 EP 1616 DI 10.1161/01.STR.0000170622.07210.b4 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 941BW UT WOS:000230190600053 PM 15961715 ER PT J AU Stylopoulos, N Davis, P Pettit, JD Rattner, DW Kaplan, LM AF Stylopoulos, N Davis, P Pettit, JD Rattner, DW Kaplan, LM TI Changes in serum ghrelin predict weight loss after Roux-en-Y gastric bypass in rats SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT 12th International Congress of the European-Association-for-Endoscopic-Surgery CY JUN 09-12, 2004 CL Barcelona, SPAIN SP European Assoc Endoscop Surg DE obesity; weight regulation; bariatric surgery; rat models; Roux-en-Y; gastric bypass; ghrelin; neuroendocrinology ID ENERGY-EXPENDITURE; MORBID-OBESITY; BODY-WEIGHT; SURGERY; OPERATION; HUMANS AB Background: Although Roux-en-Y gastric bypass (RYGB) is an effective and widely used therapy for severe obesity, the mechanisms by which it induces weight loss are not well understood. Several studies have shown that RYGB in human patients causes a decrease in circulating levels of ghrelin, a gastric hormone that strongly stimulates food intake. Substantial variation in the effect of RYGB on serum ghrelin has been reported in different studies and among individual patients, suggesting that regulation of this hormone is complex and subject to genetic and other patient-specific factors. To control for these factors and to enable more detailed study of physiologic mechanisms, we have recently developed a clinically relevant rat model of RYGB. In this study, we used this model to examine the effect of RYGB on serum ghrelin levels. Methods: Fifteen Sprague-Dawley rats that had received a high-fat diet to induce moderate obesity underwent RYGB. The operation closely resembled the procedure in humans. Serum samples were collected I month before and 3 months after RYGB, and serum ghrelin levels were measured. The primary outcomes of the study were the changes in body weight, food intake, and circulating ghrelin levels after RYGB. A multiple linear regression model was developed to examine the relationship between ghrelin levels and weight change after RYGB. Results: Three months after the procedure, RYGB-treated rats weighed 20 +/- 5% less than they would have, had they not undergone the procedure. Despite the weight loss, serum ghrelin levels were 38 +/- 6% lower than before surgery. There was appreciable variation in the weight loss in individual animals, and preoperative weight and pre- and postoperative ghrelin levels were the best predictors of postoperative weight loss. Thus, the animals who had the greatest weight loss were those that were heaviest before surgery. These rats had the highest preoperative and lowest postoperative ghrelin levels. Conclusions: Using our recently developed rat model of RYGB, we found that postoperative weight loss is correlated with the magnitude of the decrease in circulating ghrelin levels. This correlation provides the strongest evidence to date that altered ghrelin signaling contributes to weight loss after this operation. The lower level of circulating ghrelin after RYGB likely blunts the appetitive drive, leading to decreased food intake in these animals. C1 Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Stylopoulos, N (reprint author), Massachusetts Gen Hosp, Weight Ctr, 50 Staniford St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK46200, DK99010] NR 23 TC 34 Z9 34 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JUL PY 2005 VL 19 IS 7 BP 942 EP 946 DI 10.1007/s00464-004-8825-x PG 5 WC Surgery SC Surgery GA 957OH UT WOS:000231378700016 PM 15920683 ER PT J AU Hagendoorn, J Padera, TP Fukumura, D Jain, RK AF Hagendoorn, J Padera, TP Fukumura, D Jain, RK TI Molecular regulation of microlymphatic formation and function: Role of nitric oxide SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID GROWTH-FACTOR-C; LYMPHATIC ENDOTHELIAL-CELLS; PROGENITOR CELLS; TISSUE ISCHEMIA; IN-VIVO; SYNTHASE; LYMPHANGIOGENESIS; ANGIOGENESIS; METASTASIS; VESSELS AB Inhibition of lymphangiogenesis prevents lymphatic cancer metastasis, whereas induction of lymphangiogenesis alleviates lymphedema in experimental animal models. The number of known molecular players that govern the formation and function of the microlymphatic system is growing. Here, we review the role of nitric oxide within the regulation of lymphatic formation and function and point out key unanswered questions for its translation into clinical therapy. C1 Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R24 CA 85140, R01 CA 96915] NR 47 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JUL PY 2005 VL 15 IS 5 BP 169 EP 173 AR PII S1050-1738(05)00084-8 DI 10.1016/j.tcm.2005.06.003 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 006AD UT WOS:000234866600004 PM 16165013 ER PT J AU Barbie, DA Conlan, LA Kennedy, BK AF Barbie, DA Conlan, LA Kennedy, BK TI Nuclear tumor suppressors in space and time SO TRENDS IN CELL BIOLOGY LA English DT Review ID RETINOBLASTOMA GENE-PRODUCT; POLYMERASE-I TRANSCRIPTION; DNA-DAMAGE; CELL-CYCLE; CANCER SUSCEPTIBILITY; PREMATURE SENESCENCE; DEACETYLASE COMPLEX; ONCOGENIC RAS; PROTEIN; P53 AB Numerous studies have identified key binding partners and functional activities of nuclear tumor-suppressor proteins such as the retinoblastoma protein, p53 and BRCA1. Historically, less attention has been given to the subnuclear locations of these proteins. Here, we describe several recent studies that promote the view that regulated association with subcompartments of the nucleus is inherent to tumor-suppressor function. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02114 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Kennedy, BK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02114 USA. EM bkenn@u.washington.edu FU NIA NIH HHS [R01 AG 024287] NR 72 TC 2 Z9 2 U1 0 U2 0 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 JUL PY 2005 VL 15 IS 7 BP 378 EP 385 DI 10.1016/j.tcb.2005.05.005 PG 8 WC Cell Biology SC Cell Biology GA 952RN UT WOS:000231023300007 PM 15936946 ER PT J AU Rigato, L Ostrow, JD Tiribelli, C AF Rigato, L Ostrow, JD Tiribelli, C TI bilirubin and non-hepatic disease: a less jaundiced view - Response SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material ID DIPHOSPHO-GLUCURONOSYLTRANSFERASE 1A1; GENETIC POLYMORPHISMS; BREAST-CANCER; UGT1A1; ASSOCIATION; INDUCTION; RISK C1 Ctr Studi Fegato, Basovizza, Italy. Univ Trieste, Dept BBCM, I-34012 Trieste, Italy. Univ Washington, Sch Med, Div Gastroenterol Hepatol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. RP Tiribelli, C (reprint author), Ctr Studi Fegato, Bldg Q,Area Sci Pk, Basovizza, Italy. EM ctliver@csf.units.it NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUL PY 2005 VL 11 IS 7 BP 314 EP 315 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 953OA UT WOS:000231084900004 ER PT J AU Doupe, AJ Perkel, DJ Reiner, A Stern, EA AF Doupe, AJ Perkel, DJ Reiner, A Stern, EA TI Birdbrains could teach basal ganglia research a new song SO TRENDS IN NEUROSCIENCES LA English DT Review ID TONICALLY ACTIVE NEURONS; SACCADIC EYE-MOVEMENTS; MONKEY CAUDATE NEURONS; LONG-TERM POTENTIATION; ADULT ZEBRA FINCHES; FOREBRAIN NUCLEUS; AREA-X; CORTICOSTRIATAL NEURONS; STRIATAL INTERNEURONS; RECEPTOR ACTIVATION AB Recent advances in anatomical, physiological and histochemical characterization of avian basal ganglia neurons and circuitry have revealed remarkable similarities to mammalian basal ganglia. A modern revision of the avian anatomical nomenclature has now provided a common language for studying the function of the cortical-basal-ganglia-cortical loop, enabling neuroscientists to take advantage of the specialization of basal ganglia areas in various avian species. For instance, songbirds, which learn their vocal motor behavior using sensory feedback, have specialized a portion of their cortical-basal ganglia circuitry for song learning and production. This discrete circuit dedicated to a specific sensorimotor task could be especially tractable for elucidating the interwoven sensory, motor and reward signals carried by basal ganglia, and the function of these signals in task learning and execution. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol, Seattle, WA 98195 USA. Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Stern, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM stern@helix.mgh.harvard.edu NR 95 TC 137 Z9 138 U1 0 U2 22 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2005 VL 28 IS 7 BP 353 EP 363 DI 10.1016/j.tins.2005.05.005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 947YQ UT WOS:000230683600005 PM 15935486 ER PT J AU Tsai, HK Manola, J Abner, A Talcott, JA D'Amico, AV Beard, C AF Tsai, HK Manola, J Abner, A Talcott, JA D'Amico, AV Beard, C TI Patient-reported acute gastrointestinal toxicity in men receiving 3-dimensional conformal radiation therapy for prostate cancer with or without neoadjuvant androgen suppression therapy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate carcinoma; 3-dimensional conformal radiation therapy; neoadjuvant hormone therapy; acute toxicity; quality of life ID UNFAVORABLE-PROGNOSIS CARCINOMA; ONCOLOGY GROUP; DEFINITIVE RADIOTHERAPY; RANDOMIZED TRIAL; PLUS RADIATION; DEPRIVATION; VOLUME; IRRADIATION; GOSERELIN; EORTC AB Objective: To investigate the impact of 2 months of neoadjuvant and 2 months of concurrent hormonal therapy on the acute gastrointestinal (GI) toxicities associated with 3-dimensional conformal radiation therapy (3D-CRT) for prostate adenocarcinoma. Methods: The study cohort consisted of 80 men who underwent 3D-CRT with (n = 40) or without (n = 40) neoadjuvant and concurrent hormonal therapy. Computerized tomography-based planning occurred after neoadjuvant hormonal therapy. All patients completed a previously validated, quality-of-life self-assessment tool on 7 GI symptoms, including diarrhea, urgency, pain, rectal bleeding, cramping, mucus, and tenesmus, at baseline and weekly during radiation therapy. Results: Patients who received hormonal therapy were more likely to have T2b, T2c, T3a, or T3b (P < 0.001) or Gleason score 7, 8, or 9 (P = 0.02) disease compared to those that did not. The dose delivered to the planning target volume was 70 Gy for both groups. Median radiation treatment volume was numerically smaller for the hormone group but not to a statistically significant degree (949 vs. 1043 cc, P = 0.30). Patients who received hormonal therapy had less rectal pain (P < 0.01) and tenesmus (P = 0.02) but more rectal mucus (P = 0.03) compared to those who did not. Conclusions: Prostate gland volume reduction after androgen suppression therapy may reduce patient-reported acute GI toxicities associated with 3D-CRT for prostate cancer. (c) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Mt Auburn Hosp, Dept Radiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. RP Tsai, HK (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM htsai@partners.org NR 16 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2005 VL 23 IS 4 BP 230 EP 237 DI 10.1016/j.urolonc.2005.02.005 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 951DD UT WOS:000230908300002 PM 16018937 ER PT J AU Liljelund, P Handforth, A Homanicsc, GE Olsen, RW AF Liljelund, P Handforth, A Homanicsc, GE Olsen, RW TI GABA(A) receptor beta 3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta 3 subunit levels, EEG, and behavior SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE genomic imprinting; Angelman syndrome; epilepsy; GABA(A) receptor; knockout ID ANGELMAN-SYNDROME; A RECEPTOR; PRADER-WILLI; BETA(3) SUBUNIT; EPILEPSY; BRAIN; DELETION; MOUSE; IDENTIFICATION; CHROMOSOME-15 AB The homozygous knockout mouse for the beta 3 subunit of the GABA(A) receptor has been proposed as a model for the neurodevelopmental disorder, Angelman syndrome, based on phenotypic similarities of craniofacial abnormalities, cognitive defects, hyperactivity, motor incoordination, disturbed rest-activity cycles, and epilepsy. Since most children with Angelman syndrome are autosomal heterozygotes of maternal origin, apparently through genomic imprinting, we used gabrb3-deficient heterozygote mice of defined parental origin to investigate whether this phenotype is also maternally imprinted in mouse. Whole brain extracts showed greatly reduced beta 3 subunit levels in male mice of maternal origin but not in male mice of paternal origin. Females of both parental origin showed greatly reduced beta 3 subunit levels. Heterozygotes did not exhibit hyperactive circling behavior, convulsions, or electrographically recorded seizures. EEGs showed qualitative differences among heterozygotes, with male mice of maternal origin demonstrating more abnormalities including increased theta activity. Ethosuximide inhibited theta bursts, suggesting an alteration in the thalamocortical relay. Carbamazepine induced EEG slowing in males and EEG acceleration in females, with a larger effect in paternal-origin heterozygotes. Evidence thus suggests both parent-of-origin and gender-related components in developmental regulation of beta 3 expression, in particular, that the maternally-derived male heterozygote may carry a developmental modification resulting in less beta 3 protein, which may reflect partial genomic imprinting of the gabrb3 gene in mice. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles, Los Angeles, CA 90073 USA. Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. RP Olsen, RW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. EM ROlsen@mednet.ucla.edu NR 63 TC 29 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUN 30 PY 2005 VL 157 IS 2 BP 150 EP 161 DI 10.1016/j.devbrainres.2005.03.014 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 941ZW UT WOS:000230253700005 ER PT J AU Choi, EM Kwak, SJ Kim, YM Ha, KS Kim, JI Lee, SW Han, JA AF Choi, EM Kwak, SJ Kim, YM Ha, KS Kim, JI Lee, SW Han, JA TI COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE anoikis; bladder; cancer; COX-2; Mcl-1; Pl-3K/Akt ID FAMILIAL ADENOMATOUS POLYPOSIS; CYCLOOXYGENASE-2 INHIBITOR; INDUCED APOPTOSIS; EXPRESSION; CELECOXIB; CARCINOMA; INDUCTION; SURVIVAL; MODEL AB Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoilkis by a PI-3K inhibitor, LY294002. Furthermore, COX-2 enhanced Mcl-1 expression in the anoilkis process, implying that Mcl-1 also may be involved in mediating the survival function of COX-2. Together, these results suggest that COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway and probably by enhancement of Mcl-1 expression in human bladder cancer cells. This antianoikis effect of COX-2 may be a part of mechanisms to promote tumor development and progression. C1 Kangweon Natl Univ, Coll Med, Dept Biochem & Mol Biol, Chunchon 200701, South Korea. Dankook Univ, Coll Med, Dept Biochem, Cheonan 330714, South Korea. Hallym Univ, Coll Med, Dept Biochem, Chunchon 200702, South Korea. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Han, JA (reprint author), Kangweon Natl Univ, Coll Med, Dept Biochem & Mol Biol, Chunchon 200701, South Korea. EM gshja@kangwon.ac.kr RI KIM, JONG-IL/D-1019-2011 OI KIM, JONG-IL/0000-0002-7240-3744 NR 21 TC 16 Z9 22 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD JUN 30 PY 2005 VL 37 IS 3 BP 199 EP 203 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 945OC UT WOS:000230510800008 PM 16000874 ER PT J AU Kaila, N Somers, WS Thomas, BE Thakker, P Janz, K DeBernardo, S Tam, S Moore, WJ Yang, RY Wrona, W Bedard, PW Crommie, D Keith, JC Tsao, DHH Alvarez, JC Ni, H Marchese, E Patton, JT Magnani, JL Camphausen, RT AF Kaila, N Somers, WS Thomas, BE Thakker, P Janz, K DeBernardo, S Tam, S Moore, WJ Yang, RY Wrona, W Bedard, PW Crommie, D Keith, JC Tsao, DHH Alvarez, JC Ni, H Marchese, E Patton, JT Magnani, JL Camphausen, RT TI Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: Design, synthesis, and crystal structure in complex with E-selectin SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MIMICS; POTENT; SLE(X); NMR AB A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure. C1 Wyeth, Chem & Screening Sci, Cardiovasc & Metab Dis Res, Cambridge, MA 02140 USA. Arqule, Woburn, MA 01801 USA. GlycoTech Corp, Rockville, MD 20850 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Kaila, N (reprint author), Wyeth, Chem & Screening Sci, Cardiovasc & Metab Dis Res, 200 Cambridge Pk Dr, Cambridge, MA 02140 USA. EM nkaila@wyeth.com NR 24 TC 33 Z9 33 U1 1 U2 2 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 JUN 30 PY 2005 VL 48 IS 13 BP 4346 EP 4357 DI 10.1021/jm0500491 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 940CR UT WOS:000230121800020 PM 15974587 ER PT J AU Chan, DCM Fu, HN Forsch, RA Queener, SF Rosowsky, A AF Chan, DCM Fu, HN Forsch, RA Queener, SF Rosowsky, A TI Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with omega-carboxyalkoxy or omega-carboxy-1-alkynyl substitution in the side chain SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PNEUMOCYSTIS-CARINII; SELECTIVE INHIBITORS; MYCOBACTERIUM-AVIUM; TOXOPLASMA-GONDII; BIOLOGICAL-ACTIVITIES; SPECIES SELECTIVITY; POTENT; TRIMETHOPRIM; JIROVECI; PROPHYLAXIS AB As part of a search for dihydrofolate reductase (DHFR) inhibitors combining the high potency of piritrexim (PTX) with the high antiparasitic vs mammalian selectivity of trimethoprim (TMP), the heretofore undescribed 2,4-diamino-6-(2',5'-disubstituted benzyl)pyrido[2,3-d]pyrimidines 6-14 with O-(omega-carboxyalkyl) or omega-carboxy-1-alkynyl groups on the benzyl moiety were synthesized and tested against Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium DHFR vs rat DHFR. Three N-(2,4-diaminopteridin-6-yl)methyl)-2'-(omega-carboxy- 1-alkynyl)-dibenz[b,f]azepines (19-21) were also synthesized and tested. The pyridopyrimidine with the best combination of potency and selectivity was [2,4-diamino-5-methyl-6-[2'-(5-carboxy-1-butynyl)-5'-methoxy]benzyl]pyrimidine (13), with an IC50 value of 0.65 nM against P. carinii DHFR, 0.57 nM against M. avium DHFR, and 55 nM against rat DHFR. The potency of 13 against P. carinii DHFR was 20-fold greater than that of PTX (IC50 = 13 nM), and its selectivity index (SI) relative to rat DHFR was 85, whereas PTX was nonselective. The activity of 13 against P. carinii DHFR was 20 000 times greater than that of TMP, with an SI of 96, whereas that of TMP was only 14. However 13 was no more potent than PTX against M. avium DHFR, and its SI was no better than that of TMP. Molecular modeling dynamics studies using compounds 10 and 13 indicated a slight binding preference for the latter, in qualitative agreement with the IC50 data. Among the pteridines, the most potent against P. carinii DHFR and M. avium DHFR was the 2'-(5-carboxy-1-butynyl)dibenz[b,f]azepinyl derivative 20 (IC50 = 2.9 nM), whereas the most selective was the 2'-(5-carboxy-1-pentynyl) analogue 21, with SI values of > 100 against both P. carinii and M. avium DHFR relative to rat DHFR, The final compound, 2,4-diamino-5-[3'-(4-carboxy-1-butynyl)-4'-bromo-5'-mothoxybenzyl]pyrimidine (22), was both potent and selective against M. avium DHFR (IC50 = 0.47 nM, SI = 1300) but was not potent or selective against either P. carinii or T. gondii DHFR. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andre-rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI29904] NR 28 TC 42 Z9 43 U1 0 U2 6 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 JUN 30 PY 2005 VL 48 IS 13 BP 4420 EP 4431 DI 10.1021/jm0581718 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 940CR UT WOS:000230121800027 PM 15974594 ER PT J AU Huntly, BJP Gilliland, DG AF Huntly, BJP Gilliland, DG TI Cancer biology - Summing up cancer stem cells SO NATURE LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC RESPONSES; IDENTIFICATION C1 Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Huntly, BJP (reprint author), Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. EM bjph2@cam.ac.uk; ggilliland@rics.bwh.harvard.edu RI huntly, brian/E-6725-2014 OI huntly, brian/0000-0003-0312-161X NR 9 TC 84 Z9 92 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 30 PY 2005 VL 435 IS 7046 BP 1169 EP 1170 DI 10.1038/4351169a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 940JJ UT WOS:000230140500024 PM 15988505 ER PT J AU Ryan, DP Fernandez-del Castillo, C Willett, CG Brugge, WR Sahani, D Brachtel, EF Sahani, D AF Ryan, DP Fernandez-del Castillo, C Willett, CG Brugge, WR Sahani, D Brachtel, EF Sahani, D TI A 58-year-old man with locally advanced pancreatic cancer - Ductal adenocarcinoma of the pancreas, with residual microscopic tumor after chemoradiation therapy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; RESECTED ADENOCARCINOMA; ADJUVANT IRRADIATION; CURATIVE RESECTION; RADIATION-THERAPY; HELICAL CT; CHEMOTHERAPY; CARCINOMA; PHASE; PANCREATICODUODENECTOMY C1 Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. NR 26 TC 3 Z9 3 U1 0 U2 1 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 JUN 30 PY 2005 VL 352 IS 26 BP 2734 EP 2741 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 940HH UT WOS:000230133800012 PM 15987923 ER PT J AU Elman, I Ariely, D Mazar, N Aharon, I Lasko, NB Macklin, ML Orr, SP Lukas, SE Pitman, RK AF Elman, I Ariely, D Mazar, N Aharon, I Lasko, NB Macklin, ML Orr, SP Lukas, SE Pitman, RK TI Probing reward function in post-traumatic stress disorder with beautiful facial images SO PSYCHIATRY RESEARCH LA English DT Article DE stress disorders; post-traumatic; face; beauty; reward ID POST-TRAUMATIC STRESS; ADDICTION; PTSD; BIAS AB Reward dysfunction may be implicated in post-traumatic stress disorder (PTSD). This,study applied a behavioral probe, known to activate brain reward regions, to subjects with PTSD. Male heterosexual Vietnam veterans with (n = 12) or without (n = 11) current PTSD were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. There were no significant group differences in the attractiveness ratings. However, PTSD patients expended less effort to extend the viewing time of the beautiful female faces. These findings suggest a reward deficit in PTSD. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, McLean Hosp, Sch Med, Behav Psychopharmacol Res Lab,Dept Psychiat, Belmont, MA 02478 USA. MIT, Program Media Arts & Sci, Cambridge, MA 02139 USA. MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH 03104 USA. RP Elman, I (reprint author), Harvard Univ, McLean Hosp, Sch Med, Behav Psychopharmacol Res Lab,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM ielman@partners.org RI Mazar, Nina/B-7697-2011 OI Mazar, Nina/0000-0001-8248-654X FU NIDA NIH HHS [DA 17959, DA 00343] NR 19 TC 37 Z9 37 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 30 PY 2005 VL 135 IS 3 BP 179 EP 183 DI 10.1016/j.psychres.2005.04.002 PG 5 WC Psychiatry SC Psychiatry GA 951YZ UT WOS:000230969600002 PM 15993948 ER PT J AU Stewart, CR Tseng, AA Mok, YF Staples, MK Schiesser, CH Lawrence, LJ Varghese, JN Moore, KJ Howlett, GJ AF Stewart, CR Tseng, AA Mok, YF Staples, MK Schiesser, CH Lawrence, LJ Varghese, JN Moore, KJ Howlett, GJ TI Oxidation of low-density lipoproteins induces amyloid-like structures that are recognized by macrophages SO BIOCHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUE; FOAM CELL-FORMATION; OXIDIZED PHOSPHOLIPIDS; P-COMPONENT; SCAVENGER RECEPTORS; ALZHEIMERS-DISEASE; HUMAN SERUM; PROTEIN; LDL; CD36 AB The macrophage scavenger receptor CD36 plays a key role in the initiation of atherosclerosis through its ability,to bind to and internalize oxidized low-density lipoproteins (oxLDL). Prompted by recent findings that the CD36 receptor also recognizes, amyloid fibrils formed by beta-amyloid and apolipoprotein C-II, we investigated whether the oxidation of low-density lipoproteins (LDL) generates characteristic amyloid-like structures and whether these structures serve as CD36 ligands. Our studies demonstrate that LDL oxidized by copper ions, 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), or ozone react with the diagnostic amyloid dyes thioflavin T and Congo Red and bind to serum amyloid P component (SAP), a universal constituent of physiological amyloid deposits. X-ray powder diffraction patterns for native LDL show a diffuse powder diffraction ring with maximum intensity corresponding to an atomic spacing of similar to 4.7 angstrom, consistent with the spacing between beta-strands in a beta-sheet. Ozone treatment of LDL generates an additional diffuse powder diffraction ring with maximum intensity indicating a spacing of similar to 9.8 angstrom. This distance is consistent with the presence of cross-beta-structure, a defining characteristic of amyloid. Evidence that these cross-p-amyloid structures in oxLDL are recognized by macrophages is provided by the observation that SAP strongly inhibits the association and internalization of I-125-labeled copper-oxidized LDL by peritoneal macrophages. The ability of SAP to bind to amyloid-like structures in oxLDL and prevent lipid uptake by macrophages highlights the potential importance of these structures and suggests an important preventative role for SAP in foam cell formation and early-stage atherosclerosis. C1 Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Parkville, Vic 3010, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Univ Melbourne, Sch Chem, Parkville, Vic 3010, Australia. CSIRO, Parkville, Vic 3052, Australia. RP Howlett, GJ (reprint author), Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Parkville, Vic 3010, Australia. EM ghowlett@unimelb.edu.au RI Stewart, Cameron/E-6823-2011; Varghese, Joseph/A-8191-2012; Waddington, Lynne/H-3500-2013; OI Moore, kathryn/0000-0003-2505-2547 FU NIA NIH HHS [R01 AG20255] NR 46 TC 41 Z9 45 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 28 PY 2005 VL 44 IS 25 BP 9108 EP 9116 DI 10.1021/bi050497v PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939HN UT WOS:000230063300018 PM 15966734 ER PT J AU Kovalenko, OV Metcalf, DG DeGrado, WF Hemler, ME AF Kovalenko, OV Metcalf, DG DeGrado, WF Hemler, ME TI Structural organization and interactions of transmembrane domains in tetraspanin proteins SO BMC STRUCTURAL BIOLOGY LA English DT Article ID DISULFIDE CROSS-LINKING; HELIX-HELIX PACKING; INTO-HOLES PACKING; MEMBRANE-PROTEINS; COILED COILS; EXTRACELLULAR DOMAIN; DIMERIZATION MOTIF; CD9-DEFICIENT MICE; LEUCINE-ZIPPER; GAMETE FUSION AB Background: Proteins of the tetraspanin family contain four transmembrane domains (TM1-4) linked by two extracellular loops and a short intracellular loop, and have short intracellular N- and C-termini. While structure and function analysis of the larger extracellular loop has been performed, the organization and role of transmembrane domains have not been systematically assessed. Results: Among 28 human tetraspanin proteins, the TM1-3 sequences display a distinct heptad repeat motif (abcdefg)(n.) In TM1, position a is occupied by structurally conserved bulky residues and position d contains highly conserved Asn and Gly residues. In TM2, position a is occupied by conserved small residues (Gly/Ala/Thr), and position d has a conserved Gly and two bulky aliphatic residues. In TM3, three a positions of the heptad repeat are filled by two leucines and a glutamate/ glutamine residue, and two d positions are occupied by either Phe/Tyr or Val/Ile/Leu residues. No heptad motif is apparent in TM4 sequences. Mutations of conserved glycines in human CD9 (Gly25 and Gly32 in TM1; Gly67 and Gly74 in TM2) caused aggregation of mutant proteins inside the cell. Modeling of the TM1-TM2 interface in CD9, using a novel algorithm, predicts tight packing of conserved bulky residues against conserved Gly residues along the two helices. The homodimeric interface of CD9 was mapped, by disulfide cross-linking of single-cysteine mutants, to the vicinity of residues Leu14 and Phe17 in TM1 ( positions g and c) and Gly77, Gly80 and Ala81 in TM2 ( positions d, g and a, respectively). Mutations of a and d residues in both TM1 and TM2 ( Gly25, Gly32, Gly67 and Gly74), involved in intramolecular TM1-TM2 interaction, also strongly diminished intermolecular interaction, as assessed by cross-linking of Cys80. Conclusion: Our results suggest that tetraspanin intra- and intermolecular interactions are mediated by conserved residues in adjacent, but distinct regions of TM1 and TM2. A key structural element that defines TM1- TM2 interaction in tetraspanins is the specific packing of bulky residues against small residues. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Penn, Dept Biochem & Biophys, Sch Med, Philadelphia, PA 19104 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM oleg_kovalenko@dfci.harvard.edu; doug.metcalf@gmail.com; wdegrado@mail.med.upenn.edu; martin_hemler@dfci.harvard.edu FU NIGMS NIH HHS [GM38903, R01 GM038903] NR 72 TC 52 Z9 53 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD JUN 28 PY 2005 VL 5 AR 11 DI 10.1186/1472-6807-5-11 PG 20 WC Biophysics SC Biophysics GA 997YB UT WOS:000234283800003 PM 15985154 ER PT J AU Wiviott, SD Antman, EM Winters, KJ Weerakkody, G Murphy, SA Behounek, BD Carney, RJ Lazzam, C McKay, RG McCabe, CH Braunwald, E AF Wiviott, SD Antman, EM Winters, KJ Weerakkody, G Murphy, SA Behounek, BD Carney, RJ Lazzam, C McKay, RG McCabe, CH Braunwald, E CA JUMBO-TIMI 26 Investigators TI Randomized comparison of Prasugrel (CS-747, LY640315), a novel thienopyridine P2Y(12) antagonist, with clopidogrel in percutaneous coronary intervention - Results of the joint utilization of medications to block platelets optimally (JUMBO)-TIMI 26 trial SO CIRCULATION LA English DT Article DE coronary disease; drugs; hemorrhage; platelets; stents ID ACUTE MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; TASK-FORCE; TICLOPIDINE; ASPIRIN; STENT; RESISTANCE; PRETREATMENT; PLACEMENT; ANTICOAGULATION AB Background - Despite the current standard antiplatelet regimen of aspirin and clopidogrel ( with or without glycoprotein IIb/ IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel ( CS- 747, LY640315), a novel potent thienopyridine P2Y(12) receptor antagonist, has the potential to achieve higher levels of inhibition of ADP- induced platelet aggregation than currently approved doses of clopidogrel. Methods and Results - Joint Utilization of Medications to Block Platelets Optimally - Thrombolysis In Myocardial Infarction 26 ( JUMBO- TIMI 26) was a phase 2, randomized, dose- ranging, double- blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant ( TIMI major plus minor) non - CABG- related bleeding events in prasugrel- versus clopidogrel- treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding ( 1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel- treated patients, there were numerically lower incidences of the primary efficacy composite end point ( 30- day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis. Conclusions - In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety. C1 Harvard Univ, Div Cardiovasc, TIMI Study Grp, Sch Med,Brigham & Womens Hosp, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Sankyo Co Ltd, Tokyo 140, Japan. Mother Francis Hosp, Tyler, TX USA. Trillium Hlth Ctr, Mississauga, ON, Canada. Hartford Hosp, Hartford, CT 06115 USA. RP Wiviott, SD (reprint author), Harvard Univ, Div Cardiovasc, TIMI Study Grp, Sch Med,Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 31 TC 276 Z9 288 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 JUN 28 PY 2005 VL 111 IS 25 BP 3366 EP 3373 DI 10.1161/CIRCULATIONAHA.104.502815 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 939ZJ UT WOS:000230112400006 PM 15967851 ER PT J AU Zhang, SW Picard, MH Vasile, E Zhu, Y Raffai, RL Weisgraber, KH Krieger, M AF Zhang, SW Picard, MH Vasile, E Zhu, Y Raffai, RL Weisgraber, KH Krieger, M TI Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice SO CIRCULATION LA English DT Article DE apolipoproteins; atherosclerosis; diet; myocardial infarction; receptors ID HIGH-DENSITY-LIPOPROTEIN; SR-BI; HDL RECEPTOR; LIPID-METABOLISM; E POLYMORPHISM; HEART-DISEASE; HYPERCHOLESTEROLEMIA; OVEREXPRESSION; EXPRESSION; CLEARANCE AB Background - Normal chow ( low fat) - fed mice deficient in both the HDL receptor SR- BI and apolipoprotein E ( SR- BI/ apoE dKO) provide a distinctive model of coronary heart disease ( CHD). They exhibit early- onset hypercholesterolemia characterized by unesterified cholesterol - rich abnormal lipoproteins ( lamellar/ vesicular and stacked discoidal particles), occlusive coronary atherosclerosis, spontaneous myocardial infarction, cardiac dysfunction, and premature death ( approximate to 6 weeks of age). Mice in which similar features of CHD could be induced with a lipid- rich diet would represent a powerful tool to study CHD. Methods and Results - To generate a diet- inducible model of CHD, we bred SR- BI - deficient ( SR- BI KO) mice with hypomorphic apolipoprotein E mice ( ApoeR61(h/h)) that express reduced levels of an apoE4- like murine apoE isoform and exhibit diet- induced hypercholesterolemia. When fed a normal chow diet, SR- BI KO/ ApoeR61(h/h) h mice did not exhibit early- onset atherosclerosis or CHD; the low expression level of the apoE4- like murine apoE was atheroprotective and cardioprotective. However, when fed an atherogenic diet rich in fat, cholesterol, and cholate, they rapidly developed hypercholesterolemia, atherosclerosis, and CHD, a response strikingly similar to that of SR- BI/ apoE dKO mice fed a chow diet, and they died 32 +/- 6 days ( 50% mortality) after initiation of the high- fat feeding. Conclusions - The SR- BI KO/ ApoeR61(h/h) mouse is a new model of diet- induced occlusive coronary atherosclerosis and CHD ( myocardial infarction, cardiac dysfunction and premature death), allowing control of the age of onset, duration, severity, and possibly regression of disease. Thus, SR- BI KO/ ApoeR61(h/h) mice have the potential to contribute to our understanding of CHD and its prevention and treatment. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Surg, Div Vasc Surg, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Res Ctr, San Francisco, CA USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Neurol Dis, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Neurol Dis, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Krieger, M (reprint author), MIT, Dept Biol, Room 68-483,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM krieger@mit.edu OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-66105, HL-47660, HL-64737] NR 33 TC 69 Z9 71 U1 2 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 JUN 28 PY 2005 VL 111 IS 25 BP 3457 EP 3464 DI 10.1161/CIRCULATIONAHA.104.523563 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 939ZJ UT WOS:000230112400017 PM 15967843 ER PT J AU Rossi, DJ Bryder, D Zahn, JM Ahlenius, H Sonu, R Wagers, AJ Weissman, IL AF Rossi, DJ Bryder, D Zahn, JM Ahlenius, H Sonu, R Wagers, AJ Weissman, IL TI Cell intrinsic alterations underlie hematopoietic stem cell aging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE leukemia; microarray; ontogeny; lineage potential ID GENE-EXPRESSION PROFILE; IN-VIVO PROLIFERATION; AGE-RELATED-CHANGES; BONE-MARROW; TRANSCRIPTIONAL PROFILE; CALORIC RESTRICTION; LINEAGE COMMITMENT; MICE; CAPACITY; IDENTIFICATION AB Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Rossi, DJ (reprint author), Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. EM drossi@stanford.edu; irv@stanford.edu RI Ahlenius, Henrik/L-8660-2015 OI Ahlenius, Henrik/0000-0001-8958-6148 FU NCI NIH HHS [R01 CA086065, 5 R01 CA86065] NR 44 TC 456 Z9 478 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 28 PY 2005 VL 102 IS 26 BP 9194 EP 9199 DI 10.1073/pnas.0503280102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 941CD UT WOS:000230191400021 PM 15967997 ER PT J AU Prochazka, AV Lundahl, K Pearson, W Oboler, SK Anderson, RJ AF Prochazka, AV Lundahl, K Pearson, W Oboler, SK Anderson, RJ TI Support of evidence-based guidelines for the annual physical examination - A survey of primary care providers SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PERIODIC HEALTH EXAMINATION AB Background: Current evidence does not support an annual screening physical examination for asymptomatic adults, but little is known about primary care provider (PCP) attitudes and practices regarding an annual physical examination. Methods: We conducted a postal survey (32 items) of attitudes and practices regarding the annual physical examination (in asymptomatic patients 18 years or older) of a random sample of PCPs (specializing in internal medicine, family practice, and obstetrics/gynecology) from 3 geographic areas (Boston, Mass; Denver, Colo; and San Diego, Calif). Results: Respondents included 783 (47%) of 1679 PCPs. Overall, 430 (65%) of 664 agreed that an annual physical examination is necessary. Three hundred ninety-three (55%) of 712 disagreed with the statement that national organizations do not recommend an annual physical examination, and 641 (88%) of 726 perform such examinations. Most PCPs agreed that an annual physical examination provides time to counsel patients about preventive health services (696/739 [94%]), improves patient-physician relationships (693/737 [94%]), and is desired by most patients (572/737 [78%]). Most also believe that an annual physical examination improves detection of subclinical illness (545/738 [74%]) and is of proven value (461/736 [63%]). Many believed that tests should be part of an annual physical examination, including mammography (44%), a lipid panel (48%), urinalysis (44%), testing of blood glucose level (46%), and complete blood cell count (39%). Conclusions: Despite contrary evidence, most PCPs believe an annual physical examination detects subclinical illness, and many report performing unproven screening laboratory tests. Primary care providers do not appear to accept recommendations that annual physical examinations be abandoned in favor of a more selective approach to preventing health problems. C1 Denver Vet Affairs Med Ctr, Ambulatory Care Sect 11B, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Boulder, CO 80309 USA. RP Prochazka, AV (reprint author), Denver Vet Affairs Med Ctr, Ambulatory Care Sect 11B, 1055 Clermont, Denver, CO 80220 USA. EM Allan.Prochazka@med.va.gov NR 20 TC 49 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2005 VL 165 IS 12 BP 1347 EP 1352 DI 10.1001/archinte.165.12.1347 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 940BR UT WOS:000230119200003 PM 15983282 ER PT J AU Claudepierre, T Manglapus, MK Marengi, N Radner, S Champliaud, MF Tasanen, K Bruckner-Tuderman, L Hunter, DD Brunken, WJ AF Claudepierre, T Manglapus, MK Marengi, N Radner, S Champliaud, MF Tasanen, K Bruckner-Tuderman, L Hunter, DD Brunken, WJ TI Collagen XVII and BPAG1 expression in the retina: Evidence for an anchoring complex in the central nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE extracellular matrix; synaptogenesis; photoreceptor; CNS development; hemidesmosomes ID CONGENITAL MUSCULAR-DYSTROPHY; BULLOUS PEMPHIGOID ANTIGEN-1; LAMININ BETA-2 CHAIN; BASEMENT-MEMBRANE; DIFFERENTIAL DISTRIBUTION; TRANSMEMBRANE PROTEIN; EPIDERMOLYSIS-BULLOSA; GLYCOPROTEIN COMPLEX; SYNAPTIC CLEFT; CELL-SURFACE AB The ectoderm gives rise not only to the skin but also to the entire CNS. This common embryonic lineage suggests that some molecular isoforms might serve analogous functions in both tissues. Indeed, not only are laminins important components of dermal adhesion mechanisms, but they also regulate some aspects of synaptic development in both the CNS and the PNS. In the skin, laminins are part of a hemidesmosome complex essential for basal keratinocyte adhesion that includes collagen XVII (BP180) and BPAG1 (dystonin/BP230). Here, we show that CNS neurons also express collagen XVII and BPAG1 and that these molecules are expressed in the adult and developing retina. In the retina, isoforms of collagen XVII and BPAG1 are colocalized with laminins at photoreceptor synapses and around photoreceptor outer segments; both molecules are expressed by rods, whereas cones express collagen XVII but not BPAG1. Moreover, biochemical data demonstrate that collagen XVII complexes with retinal laminins. We propose that collagen XVII and BPAG1 isoforms may help to anchor elements of the rod photoreceptor cytomatrix to the extracellular matrix. C1 Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Tufts Ctr Vis Res, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Oulu, Dept Dermatol, FIN-90230 Oulu, Finland. Univ Freiburg, Dept Dermatol, D-79104 Freiburg, Germany. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Brunken, WJ (reprint author), Tufts Univ, Sch Med, Dept Anat & Cellular Biol, 136 Harrison Ave,M&V 142, Boston, MA 02111 USA. EM bill.brunken@tufts.edu OI Brunken, William J/0000-0001-7330-1814 FU NEI NIH HHS [P30 EY013078, P30EY13078, R01 EY012676, R01 EY012676-06, R01EY12037, R01EY12676]; NINDS NIH HHS [R01 NS039502, R01NS39502] NR 63 TC 36 Z9 39 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 27 PY 2005 VL 487 IS 2 BP 190 EP 203 DI 10.1002/cne.20549 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 929DU UT WOS:000229323100006 PM 15880472 ER PT J AU Mezrich, JD Benjamin, LC Sachs, JA Houser, SL Vagefi, PA Sachs, DH Madsen, JC Yamada, K AF Mezrich, JD Benjamin, LC Sachs, JA Houser, SL Vagefi, PA Sachs, DH Madsen, JC Yamada, K TI Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine SO TRANSPLANTATION LA English DT Article DE transplantation; tolerance; suppression; anergy; major histocompatibility complex; cytotoxic T lymphocyte ID CARDIAC ALLOGRAFT VASCULOPATHY; CLASS-I-DISPARATE; MAJOR HISTOCOMPATIBILITY COMPLEX; RENAL-ALLOGRAFTS; TRANSPLANTATION TOLERANCE; INTERNATIONAL-SOCIETY; LUNG-TRANSPLANTATION; IMMUNE-MECHANISMS; INDUCTION; COTRANSPLANTATION AB Background. The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. Methods. Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group I animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). Results. Group I animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. Conclusions. Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. RP Yamada, K (reprint author), Transplantat Biol Res Ctr, MGH-East,13th St,CNY-149,9019, Charlestown, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL 54211-08]; NIAID NIH HHS [R01 AI 31046] NR 26 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2005 VL 79 IS 12 BP 1663 EP 1673 DI 10.1097/01.TP.0000160679.04441.B7 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 938ZJ UT WOS:000230041600005 PM 15973167 ER PT J AU Noguchi, H Matsushita, M Matsumoto, S Lu, YF Matsui, H Bonner-Weir, S AF Noguchi, H Matsushita, M Matsumoto, S Lu, YF Matsui, H Bonner-Weir, S TI Mechanism of PDX-1 protein transduction SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE islet transplantation; regeneration; PDX-1; protein transduction domain; endocytosis; endosomal release ID CELL-PENETRATING PEPTIDES; ISLET TRANSPLANTATION; ENGRAILED HOMEOPROTEIN; HOMEOBOX FACTOR; INSULIN GENE; DELIVERY; TAT; TRANSCRIPTION; HOMEODOMAIN; EXPRESSION AB PDX-1 plays a central role in differentiation of insulin-producing cells. We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells. These data suggest a strategy for facilitating differentiation into insulin-producing cells. Here we show the mechanism of PDX-1 protein transduction. Initially, a punctate cytoplasmic distribution of PDX-1 protein transduction domain (PTD), which co-localized with an endosomal marker, was observed in treated cells. However, homogeneous distribution of PDX-1-PTD was observed in some cells, indicating that PDX-1 is transduced by endocytosis and then released. The experiments using inhibitors suggested that the PDX-1 is transported through the Golgi complex and to the endoplasmic reticulum. Moreover, we observed in real-time PDX-1-PTD release from endosomes. These data suggest that mechanism of transduction of PDX-1 protein is by endocytosis and subsequent release from the endosome homogeneously in cytoplasm and nuclei, and that PDX-1 protein transduction could be a valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat & Immunol, Sakyo Ku, Kyoto 6068507, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Physiol, Okayama 7008558, Japan. Okayama Univ, Grad Sch Med & Dent, Japan Sci & Technol Corp, Off Technol Transfer,Preventure Program, Okayama 7008558, Japan. RP Noguchi, H (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM noguchih@kuhp.kyoto-u.ac.jp OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [DK 44523, DK 61251, DK36836] NR 40 TC 47 Z9 49 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 24 PY 2005 VL 332 IS 1 BP 68 EP 74 DI 10.1016/j.bbrc.2005.04.092 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 929OK UT WOS:000229355200011 PM 15896300 ER PT J AU Yellaturu, CR Deng, X Cagen, LM Wilcox, HG Park, EA Raghow, R Elam, MB AF Yellaturu, CR Deng, X Cagen, LM Wilcox, HG Park, EA Raghow, R Elam, MB TI Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SREBP-1; insulin; cAMP; hepatocyte; insig; ubiquitin ID ELEMENT-BINDING PROTEIN-1C; CHOLESTEROL HOMEOSTASIS; MESSENGER-RNA; SCAP; INSIG-1; LIPOGENESIS; EXPRESSION; GENE; OVEREXPRESSION; PATHWAY AB Insulin and cAMP have opposing effects on de novo fatty acid synthesis in liver and in cultured hepatocytes mediated by sterol-regulatory element binding protein (SREBP). To determine whether these agents regulate the cleavage of full-length SREBP to generate the transcriptionally active N-terminal fragment (nSREBP) in primary rat hepatocytes, an adenoviral vector (Ad-SREBP-1a) was constructed to constitutively express full-length SREBP-la. Insulin increased, and dibutyryl (db)-cAMP inhibited, generation of nSREBP-1a from its full-length precursor. Insulin stimulated processing of SREBP-1a within 1 h, and the effect was sustained for at least 24 h. The initial stimulation of SREBP processing by insulin preceded measurable reduction in Insig-2 mRNA levels. Rat hepatocytes were also infected with an adenovirus expressing the nuclear form of SREBP-1c (Ad-nSREBP-1c). Insulin increased the half-life of constitutively expressed nSREBP-1c, and this effect of insulin was also inhibited by db-cAMP. Published by Elsevier Inc. C1 US Dept Vet Affairs, Med Ctr, Memphis, TN USA. Univ Tennessee, Hlth Sci Ctr, Div Clin Pharmacol, Dept Pharm, Knoxville, TN 37996 USA. Univ Tennessee, Hlth Sci Ctr, Div Clin Pharmacol, Dept Med, Knoxville, TN 37996 USA. RP Cagen, LM (reprint author), US Dept Vet Affairs, Med Ctr, Memphis, TN USA. EM lcagen@utmem.edu FU NIDDK NIH HHS [DK-059368] NR 24 TC 37 Z9 39 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 24 PY 2005 VL 332 IS 1 BP 174 EP 180 DI 10.1016/j.bbrc.2005.04.112 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 929OK UT WOS:000229355200025 PM 15896314 ER PT J AU Maecker, HT Rinfret, A D'Souza, P Darden, J Roig, E Landry, C Hayes, P Birungi, J Anzala, O Garcia, M Harari, A Frank, I Baydo, R Baker, M Holbrook, J Ottinger, J Lamoreaux, L Epling, CL Sinclair, E Suni, MA Punt, K Calarota, S El-Bahi, S Alter, G Maila, H Kuta, E Cox, J Gray, C Altfeld, M Nougarede, N Boyer, J Tussey, L Tobery, T Bredt, B Roederer, M Koup, R Maino, VC Weinhold, K Pantaleo, G Gilmour, J Horton, H Sekaly, RP AF Maecker, HT Rinfret, A D'Souza, P Darden, J Roig, E Landry, C Hayes, P Birungi, J Anzala, O Garcia, M Harari, A Frank, I Baydo, R Baker, M Holbrook, J Ottinger, J Lamoreaux, L Epling, CL Sinclair, E Suni, MA Punt, K Calarota, S El-Bahi, S Alter, G Maila, H Kuta, E Cox, J Gray, C Altfeld, M Nougarede, N Boyer, J Tussey, L Tobery, T Bredt, B Roederer, M Koup, R Maino, VC Weinhold, K Pantaleo, G Gilmour, J Horton, H Sekaly, RP TI Standardization of cytokine flow cytometry assays SO BMC IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; IFN-GAMMA; MONONUCLEAR-CELLS; INTERFERON-GAMMA; ELISPOT; CRYOPRESERVATION; QUANTIFICATION; INDIVIDUALS; EXPRESSION; VIABILITY AB Background: Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment ( see additional files online). Results: Three sample types ( activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4(+) cytokine(+) cells and CD8(+) cytokine+ cells) were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation ( C. V.) ranged from 17 - 44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells ( PBMC) yielded lower inter-lab C. V.' s than whole blood. Centralized analysis ( using a dynamic gating template) reduced the inter-lab C. V. by 5 - 20%, depending upon the experiment. The inter-lab C. V. was lowest ( 18 - 24%) for samples with a mean of > 0.5% IFN gamma + T cells, and highest ( 57 - 82%) for samples with a mean of < 0.1% IFN gamma+ cells. Conclusion: ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more consistent results than shipped whole blood. Analysis, particularly gating, is a significant source of variability, and can be reduced by centralized analysis and/or use of a standardized dynamic gating template. Use of pre-aliquoted lyophilized reagents for stimulation and staining can provide further standardization to these assays. C1 BD Biosci, San Jose, CA USA. Univ Montreal, Montreal, PQ, Canada. Canadian Network Vaccines & Immunotherapeut, CANVAC, Montreal, PQ, Canada. NIAID, NIH, Bethesda, MD 20892 USA. Chelsea & Westminster Hosp, London, England. IAVI, London, England. Uganda Virus Res Inst, Entebbe, Uganda. IAVI, Entebbe, Uganda. Univ Nairobi, Kenya AIDS Vaccine Initiat, Nairobi, Kenya. CHU Vaudois, CH-1011 Lausanne, Switzerland. EUROVAC, Lausanne, Switzerland. Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC USA. HVTN, Durham, NC USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Merck & Co Inc, West Point, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Sanofi Pasteur, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Communicable Dis, Johannesburg, South Africa. Henry Jackson Fdn, Rockville, MD USA. RP BD Biosci, San Jose, CA USA. EM holden_maecker@bd.com; aline.rinfret@canvac.ca; pdsouza@niaid.nih.gov; jdarden@niaid.nih.gov; roigpatault@videotron.ca; claire.landry@umontreal.ca; p.hayes@ic.ac.uk; jbirungi@iavi.org; oanzala@kaviuon.org; miguel.garcia@chuv.hospvd.ch; alexandre.harari@chuv.hospvd.ch; ifrank@fhcrc.org; rbaydo@fhcrc.org; mcbaker@duke.edu; jaholbro@duke.edu; jotti@duke.edu; llamorea@nih.gov; lepling@medsfgh.ucsf.edu; esinclair@gladstone.ucsf.edu; maria_suni@bd.com; kara_punt@merck.com; calarota@mail.med.upenn.edu; selbahi@free.fr; galter@partners.org; hazelm@nicd.ac.za; ekuta@hivresearch.org; jcox@hivresearch.org; cgray@nicd.ac.za; maltfeld@partners.org; nolwenn.nougarede@aventis.com; boyerj@mail.med.upenn.edu; lynda.tussey@vaxinnate.com; timothy_tobery@merck.com; barryb@itsa.ucsf.edu; roederer@nih.gov; rkoup@mail.nih.gov; smaino@bd.com; kjw@duke.edu; giuseppe.pantaleo@chuv.hospvd.ch; jgilmour@iavi.org; hhorton@fhcrc.org; rafick-pierre.sekaly@umontreal.ca RI Pantaleo, Giuseppe/K-6163-2016; OI Harari, Alexandre/0000-0002-1055-2090 NR 34 TC 117 Z9 124 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD JUN 24 PY 2005 VL 6 AR UNSP 13 DI 10.1186/1471-2172-6-13 PG 18 WC Immunology SC Immunology GA 017SN UT WOS:000235713700001 PM 15978127 ER PT J AU Park, WH Margossian, S Horwitz, AA Simons, AM D'Andrea, AD Parvin, JD AF Park, WH Margossian, S Horwitz, AA Simons, AM D'Andrea, AD Parvin, JD TI Direct DNA binding activity of the Fanconi anemia D2 protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; BRANCH MIGRATION; NUCLEAR-COMPLEX; PATHWAY; FANCD2; BRCA2; FIBROBLASTS; DEFICIENT; GENE AB It is known that the Fanconi anemia D2 protein is vital for protecting the genome from DNA damage, but what activities this protein has are unknown. In these experiments we purified full-length Fanconi anemia protein D2 (FANCD2), and we found that FANCD2 bound to DNA with specificity for certain structures: double strand DNA ends and Holliday junctions. Proteins containing patient-derived mutations or artificial variants of the FANCD2 protein were similarly expressed and purified, and each variant bound to the Holliday junction DNA with similar affinity as did the wild-type protein. There was no single discrete domain of FANCD2 protein that bound to DNA, but rather the full-length protein was required for structure-specific DNA binding. This finding of DNA binding is the first biochemical activity identified for this key protein in the Fanconi anemia pathway. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Parvin, JD (reprint author), Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM JParvin@rics.bwh.harvard.edu RI Parvin, Jeffrey/C-8955-2009 FU NCI NIH HHS [CA090281] NR 39 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23593 EP 23598 DI 10.1074/jbc.M503730200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000024 PM 15849361 ER PT J AU Shin, YG Klucken, J Patterson, C Hyman, BT McLean, PJ AF Shin, YG Klucken, J Patterson, C Hyman, BT McLean, PJ TI The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; E3 UBIQUITIN LIGASE; LEWY BODY DISEASE; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; HUNTINGTONS-DISEASE; DROSOPHILA MODEL; IN-VITRO; BODIES; AGGREGATION AB alpha-Synuclein is a major component of Lewy bodies, the pathological hallmark of Parkinson disease, dementia with Lewy bodies, and related disorders. Misfolding and aggregation of alpha-synuclein is thought to be a critical cofactor in the pathogenesis of certain neurodegenerative diseases. In the current study, we investigate the role of the carboxyl terminus of Hsp70-interacting protein ( CHIP) in alpha-synuclein aggregation. We demonstrate that CHIP is a component of Lewy bodies in the human brain, where it colocalizes with alpha-synuclein and Hsp70. In a cell culture model, endogenous CHIP colocalizes with alpha-synuclein and Hsp70 in intracellular inclusions, and overexpression of CHIP inhibits alpha-synuclein inclusion formation and reduces alpha-synuclein protein levels. We demonstrate that CHIP can mediate alpha-synuclein degradation by two discrete mechanisms that can be dissected using deletion mutants; the tetratricopeptide repeat domain is critical for proteasomal degradation, whereas the U-box domain is sufficient to direct alpha-synuclein toward the lysosomal degradation pathway. Furthermore, alpha-synuclein, synphilin-1, and Hsp70 all co-immunoprecipitate with CHIP, raising the possibility of a direct alpha-synuclein-CHIP interaction. The fact that the tetratricopeptide repeat domain is required for the effects of CHIP on alpha-synuclein inclusion morphology, number of inclusions, and proteasomal degradation as well as the direct interaction of CHIP with Hsp70 implicates a cooperation of CHIP and Hsp70 in these processes. Taken together, these data suggest that CHIP acts a molecular switch between proteasomal and lysosomal degradation pathways. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. Univ N Carolina, Carolina Cardiovasc Biol Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. RP McLean, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Dis Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org FU NIA NIH HHS [AG05134-20]; NIMH NIH HHS [1R24MH68855]; NINDS NIH HHS [NS 38372] NR 62 TC 169 Z9 181 U1 4 U2 15 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 JUN 24 PY 2005 VL 280 IS 25 BP 23727 EP 23734 DI 10.1074/jbc.M503326200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000041 PM 15845543 ER PT J AU Jean-Rene, B Gardella, TJ Dean, T MacLean, S Potetinova, Z Whitfield, JF Willick, GE AF Jean-Rene, B Gardella, TJ Dean, T MacLean, S Potetinova, Z Whitfield, JF Willick, GE TI Backbone-methylated analogues of the principle receptor binding region of human parathyroid hormone - Evidence for binding to both the N-terminal extracellular domain and extracellular loop region SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PTH/PTHRP RECEPTOR; CIRCULAR-DICHROISM; SIDE-CHAIN; BIOLOGICAL-ACTIVITIES; CONSTRAINED ANALOGS; ADENYLYL-CYCLASE; BONE-GROWTH; FRAGMENTS; PEPTIDES AB We have used backbone N-methylations of parathyroid hormone (PTH) to study the role of these NH groups in the C-terminal amphiphilic alpha-helix of PTH (1-31) in binding to and activating the PTH receptor (P1R). The circular dichroism ( CD) spectra indicated the structure of the C-terminal alpha-helix was locally disrupted around the methylation site. The CD spectra differences were explained by assuming a helix disruption for four residues on each side of the site of methylation and taking into account the known dependence of CD on the length of an alpha-helix. Binding and adenylyl cyclase-stimulating data showed that outside of the alpha-helix, methylation of residues Asp(30) and Val(31) had little effect on structure or activities. Within the alpha-helix, disruption of the structure was associated with increased loss of activity, but for specific residues Val(21), Leu(24), Arg(25), and Leu(28) there was a dramatic loss of activities, thus suggesting a more direct role of these NH groups in correct P1R binding and activation. Activity analyses with P1R-delNT, a mutant with its long N-terminal region deleted, gave a different pattern of effects and implicated Ser(17), Trp(23), and Lys(26) as important for its PTH activation. These two groups of residues are located on opposite sides of the helix. These results are compatible with the C-terminal helix binding to both the N-terminal segment and also to the looped-out extracellular region. These data thus provide direct evidence for important roles of the C-terminal domain of PTH in determining high affinity binding and activation of the P1R receptor. C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Willick, GE (reprint author), Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. EM gordon.willick@nrc.ca NR 54 TC 0 Z9 0 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 JUN 24 PY 2005 VL 280 IS 25 BP 23771 EP 23777 DI 10.1074/jbc.M500817200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000047 ER PT J AU Itoh, S Ding, B Bains, CP Wang, N Takeishi, Y Jalili, T King, GL Walsh, RA Yan, C Abe, J AF Itoh, S Ding, B Bains, CP Wang, N Takeishi, Y Jalili, T King, GL Walsh, RA Yan, C Abe, J TI Role of p90 ribosomal S6 kinase (p90RSK) in reactive oxygen species and protein kinase C beta (PKC-beta)-mediated cardiac troponin I phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; VENTRICULAR-MUSCLE; ACTOMYOSIN S-1; MOUSE HEARTS; ACTIVATION; RAS; MGATPASE; ISOFORM; SITES; VIVO AB Protein kinase C (PKC)-induced phosphorylation of cardiac troponin I (cTnI) depresses the acto-myosin interaction and may be important during the progression of heart failure. Although both PKC beta II and PKC epsilon can phosphorylate cTnI, only PKC beta expression and activity are elevated in failing human myocardium during end-stage heart failure. Furthermore, although increased cTnI phosphorylation was observed in mice with cardiac-specific PKC beta II overexpression, no differences were observed in cTnI phosphorylation status between wild type and cardiac-specific PKC epsilon overexpression mice. A potentially important downstream effector of PKCs is p90 ribosomal S6 kinase (p90RSK), which plays an important role in cell growth by activating several transcription factors as well as Na+/H+ exchanger. Since both Ser(23) and Ser(24) of cTnI are contained in putative consensus sequences of p90RSK phosphorylation sites, we hypothesized that p90RSK is downstream from PKC beta II and can be a cTnI (Ser(23/24)) kinase. p90RSK, but not ERK1/2 activation, was increased in PKC beta II overexpression mice but not in PKC epsilon overexpression mice. p90RSK could phosphorylate cTnI in vitro with high substrate affinity but not cardiac troponin T (cTnT). To confirm the role of p90RSK in cTnI phosphorylation in vivo, we generated adenovirus containing a dominant negative form of p90RSK (Ad-DN-p90RSK). We found that the inhibition of p90RSK prevented H2O2-mediated cTnI (Ser(23/24)) phosphorylation but not ERK1/2 and PKC alpha/beta II activation. Next, we generated cardiac-specific p90RSK transgenic mice and observed that cTnI (Ser(23/24)) phosphorylation was significantly increased. LY333,531, a specific PKC beta inhibitor, inhibited both p90RSK and cTnI (Ser23/24) phosphorylation by H2O2. Taken together, our data support a new redox-sensitive mechanism regulating cTnI phosphorylation in cardiomyocytes. C1 Univ Rochester, Sch Med & Dent, Inst Cardiovasc Res, Cardiol Unit, Rochester, NY 14642 USA. Univ Cincinnati, Childrens Hosp, Ctr Med, Cincinnati, OH 45229 USA. Univ Utah, Salt Lake City, UT 84112 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Abe, J (reprint author), Univ Rochester, Sch Med & Dent, Inst Cardiovasc Res, Cardiol Unit, Box 679,601 Elmwood Ave, Rochester, NY 14642 USA. EM jun-ichi_abe@urmc.rochester.edu FU NHLBI NIH HHS [HL-65262, HL-66919] NR 40 TC 42 Z9 43 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 JUN 24 PY 2005 VL 280 IS 25 BP 24135 EP 24142 DI 10.1074/jbc.M413015200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000087 PM 15840586 ER PT J AU Gratzer, W Nathan, DG AF Gratzer, W Nathan, DG TI Fred S. Rosen (1930-2005) - Immunologist, paediatrician and polymath SO NATURE LA English DT Biographical-Item C1 Univ London Kings Coll, Randall Div, London SE1 1UL, England. Childrens Hosp Boston, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gratzer, W (reprint author), Univ London Kings Coll, Randall Div, Guys Campus,New Hunts House, London SE1 1UL, England. EM wbg@helios.rai.kcl.ac.uk; David_Nathan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 23 PY 2005 VL 435 IS 7045 BP 1044 EP 1044 DI 10.1038/4351044a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 937ZT UT WOS:000229970400032 PM 15973397 ER PT J AU Kao, AY Munandar, R Ferrara, SL Systrom, DM Sheridan, RL Cash, SS Ryan, ET Ronan, L Harris, NL Llewellyn, M AF Kao, AY Munandar, R Ferrara, SL Systrom, DM Sheridan, RL Cash, SS Ryan, ET Ronan, L Harris, NL Llewellyn, M TI Respiratory distress and hemiparesis after a tsunami - Tsunami-related aspiration pneumonia with lung and brain abscesses, probably polymicrobial SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Chelsea Hlth Ctr, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Project HOPE, Task Force HOPE Mercy, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Zainoel Abidin Univ Hosp, Dept Med, Banda Aceh, Sumatra, Indonesia. US Naval Ship Mercy TAH19, Dept Radiol, San Diego, CA USA. Natl Naval Med Res Inst, Dept Radiol, San Diego, CA USA. Massachusetts Gen Hosp, Burn Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Trauma Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Kao, AY (reprint author), Massachusetts Gen Hosp, Chelsea Hlth Ctr, Dept Med, Boston, MA 02114 USA. NR 20 TC 12 Z9 12 U1 0 U2 1 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 JUN 23 PY 2005 VL 352 IS 25 BP 2628 EP 2636 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 937VJ UT WOS:000229953700012 PM 15972870 ER PT J AU Rohde, LE Clausell, N Ribeiro, JP Goldraich, L Netto, R Dec, GW DiSalvo, TG Polanczyk, CA AF Rohde, LE Clausell, N Ribeiro, JP Goldraich, L Netto, R Dec, GW DiSalvo, TG Polanczyk, CA TI Health outcomes in decompensated congestive heart failure: a comparison of tertiary hospitals in Brazil and United States SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE congestive heart failure; international; outcomes and treatment ID CHARLSON COMORBIDITY INDEX; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; RANDOMIZED-TRIAL; SURVEY PROGRAM; COUNTRIES; ADJUSTMENT; GUIDELINES; MANAGEMENT AB Background: Few international studies prospectively compared evidence-based practices and health outcomes among congestive heart failure (CHF) cohorts from countries with different cultural and economic backgrounds. Methods: Patients consecutively admitted with congestive heart failure to tertiary care teaching hospitals in Brazil and in the United States (U.S.) were systematically evaluated using a structured data form. Follow-up data 3 months after discharge were obtained using chart review and telephone interviews. Results: U.S. patients were older (p < 0.01), had higher prevalence of ischemic etiology (p < 0.01) and less previous hospitalizations for congestive heart failure (p=0.03) than Brazilian patients, but similar Charlson comorbidity scores (p=0.54) and left ventricular (LV) function (p=0.45). Prescription of angiotensin-converting enzyme inhibitors at discharge was lower at the U.S. hospital (57% vs. 68%; p=0.03), but beta-blockers prescription was higher (37% vs. 10%; p < 0.01). Length-of-stay was significantly shorter (5 [interquartile range, 3-9] vs. 11 [619] days-, p < 0.001) and in-hospital mortality was lower (2.4% vs. 13%; p < 0.001) in the U.S. cohort, but fewer clinical events within 3 months after discharge were observed in Brazilian patients (42% vs. 54%; p=0.02). Combined clinical outcomes within 3 months, including overall mortality and hospital readmission, were similar between cohorts (57% vs. 55%; p=0.80). In multivariate analysis, hospital site remained significantly associated with health outcomes. Conclusions: Medical practice and health-related outcornes were different between U.S. and Brazilian congestive heart failure patients. In order to improve management worldwide, potential factors (structural, cultural or disease-related) that might be associated with these differences need to be evaluated in future studies. (c) 2004 Published by Elsevier Ireland Ltd. C1 Univ Fed Rio Grande Sul, Sch Med, Serv Cardiol, Hosp Clin Porto Alegre,Heart Failure Unit, BR-90035003 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Sch Med, Serv Cardiol, Hosp Clin Porto Alegre,Cardiac Transplantat Unit,, BR-90035003 Porto Alegre, RS, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rohde, LE (reprint author), Univ Fed Rio Grande Sul, Sch Med, Serv Cardiol, Hosp Clin Porto Alegre,Heart Failure Unit, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM lerohde@terra.com.br RI Ribeiro, Jorge/B-5409-2010; Polanczyk, Carisi/D-6208-2013; Rohde, Luis Eduardo/I-4216-2013; Clausell, Nadine /C-7813-2016 OI Clausell, Nadine /0000-0003-4207-3809 NR 28 TC 18 Z9 20 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUN 22 PY 2005 VL 102 IS 1 BP 71 EP 77 DI 10.1016/j.ijcard.2004.04.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 937SP UT WOS:000229946100009 PM 15939101 ER PT J AU Shekelle, PG Morton, SC Suftorp, MJ Buscemi, N Friesen, C AF Shekelle, PG Morton, SC Suftorp, MJ Buscemi, N Friesen, C TI Challenges in systematic reviews of complementary and alternative medicine topics SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID LOW-BACK-PAIN; CLINICAL-TRIALS; MANIPULATIVE THERAPY; PUBLICATION BIAS; PLACEBO; METAANALYSIS; ACUPUNCTURE; DEPRESSION; STROKE AB The use of complementary and alternative medicine (CAM) continues to grow in the United States. The Agency for Healthcare Research and Quality has devoted a substantial proportion of the Evidence-based Practice Center (EPC) program to systematic reviews of CAM. Such syntheses present different challenges from those conducted on western medicine topics, and in many ways are more difficult. We discuss 3 challenges: identifying evidence about CAM, assessing the quality of individual studies, and addressing rare serious adverse events. We use illustrations from EPC evidence reports to show readers approaches to the 3 areas and then present specific recommendations for each issue. C1 RAND Corp, So Calif Evidence Based Pract Ctr, Santa Monica, CA 90401 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Shekelle, PG (reprint author), RAND Corp, So Calif Evidence Based Pract Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM Paul_Shekelle@rand.org OI Friesen, Carol/0000-0001-6437-9126 NR 33 TC 41 Z9 42 U1 1 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 JUN 21 PY 2005 VL 142 IS 12 SU S BP 1042 EP 1047 PN 2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 938CN UT WOS:000229977600003 PM 15968028 ER PT J AU Santaguida, PL Helfand, M Raina, P AF Santaguida, PL Helfand, M Raina, P TI Challenges in systematic reviews that evaluate drug efficacy or effectiveness SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; ALZHEIMER-DISEASE; NETWORK METAANALYSIS; HEALTH-POLICY; HEPATITIS-C; COMBINATION; PROGRESSION; DEMENTIA; VALIDITY; THERAPY AB Increasingly, consumers, clinicians, regulatory bodies, and insurers are using systematic reviews of drug interventions to select treatments and set policies. Although a systematic review cannot provide all the information a clinician needs to make an informed choice for therapy, it can help decision makers distinguish what claims about effectiveness are based on evidence, identify critical information gaps, describe features of the evidence that limit applicability in practice, and address whether drug effectiveness differs for particular subgroups of patients. To improve the relevance and validity of reviews of drug therapies, reviewers need to delineate clinically important subgroups, specific aims of therapy, and most important outcomes. They may need to find unpublished trials, studies other than direct comparator (head-to-head) trials, and additional details of published trials from pharmaceutical manufacturers and regulatory agencies. In this paper, we address ways to formulate questions relevant to specific clinical therapeutic aims; discuss types of studies to include in drug efficacy and effectiveness reviews and how to find them; and describe ways to assess applicability of studies to actual practice. C1 McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4L8, Canada. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Evidence Based Pract Ctr, Portland, OR USA. RP Raina, P (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, DTC Room 306,1280 Main St W, Hamilton, ON L8S 4L8, Canada. NR 38 TC 18 Z9 18 U1 0 U2 1 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 JUN 21 PY 2005 VL 142 IS 12 SU S BP 1066 EP 1072 PN 2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 938CN UT WOS:000229977600006 PM 15968031 ER PT J AU Pignone, M Saha, S Hoerger, T Lohr, KN Teutsch, S Mandelblatt, J AF Pignone, M Saha, S Hoerger, T Lohr, KN Teutsch, S Mandelblatt, J TI Challenges in systematic reviews of economic analyses SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SERVICES-TASK-FORCE; COST-EFFECTIVENESS ANALYSES; COLORECTAL-CANCER; PREVENTIVE-SERVICES; AVERAGE-RISK; GUIDELINES; QUALITY; HEALTH; RECOMMENDATIONS; UTILITY AB Economic analyses can provide valuable information for health care decision makers. Systematic reviews of economic analyses can integrate information from multiple studies and provide important insights by systematically examining how differences between models lead to different results. We use our experience in developing and implementing systematic reviews of economic analyses for the U.S. Preventive Services Task Force, particularly our systematic review of the cost-effectiveness of colorectal cancer screening, to illustrate key methodologic challenges and suggest a framework for other researchers in this area. C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR USA. RTI Univ N Carolina, Evidence Based Practice Ctr, Res Triangle Pk, NC USA. Merck & Co Inc, W Point, PA USA. Georgetown Univ, Ctr Med, Washington, DC 20057 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Pignone, M (reprint author), Univ N Carolina Hosp, Dept Med, Div Gen Internal Med, 5039 Old Clin Bldg, Chapel Hill, NC 27599 USA. EM Pignone@med.unc.edu FU NCI NIH HHS [U01CA88283A, K05CA96940] NR 26 TC 50 Z9 51 U1 0 U2 7 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 JUN 21 PY 2005 VL 142 IS 12 SU S BP 1073 EP 1079 PN 2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 938CN UT WOS:000229977600007 PM 15968032 ER PT J AU Chou, R Helfand, M AF Chou, R Helfand, M TI Challenges in systematic reviews that assess treatment harms SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ADVERSE DRUG-REACTIONS; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONFLICT-OF-INTEREST; HEALTH-CARE; CAUSALITY ASSESSMENT; BALANCING BENEFITS; GASTROINTESTINAL TOXICITY; METHODOLOGICAL QUALITY AB An evidence synthesis of a medical intervention should assess the balance of benefits and harms. Investigators performing systematic reviews of harms face challenges in finding data, rating the quality of harms reporting, and synthesizing and displaying data from different sources. Systematic reviews of harms often rely primarily on published clinical trials. Identifying important harms of treatment and quantifying the risk associated with them, however, often require a broader range of data sources, including unpublished trials, observational studies, and unpublished information on published trials submitted to the U.S. Food and Drug Administration. Each source of data has some potential for yielding important information. Criteria for judging the quality of harms assessment and reporting are still in their early stages of development. Investigators conducting systematic reviews of harms should consider empirically validating the criteria they use to judge the validity of studies reporting harms. Synthesizing harms data from different sources requires careful consideration of internal validity, applicability, and sources of heterogeneity. This article highlights examples of approaches to methodologic issues associated with performing systematic reviews of harms from 96 Evidence-based Practice Center evidence reports. C1 Oregon Hlth Sci Univ, Oregon Evidence Based Pract Ctr, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Chou, R (reprint author), Oregon Hlth Sci Univ, Oregon Evidence Based Pract Ctr, 3181 SW Sam Jackson Pk Rd,Mail Code BICC, Portland, OR 97201 USA. EM chour@ohsu.edu NR 109 TC 83 Z9 84 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 JUN 21 PY 2005 VL 142 IS 12 SU S BP 1090 EP 1099 PN 2 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 938CN UT WOS:000229977600009 PM 15968034 ER PT J AU Sabatine, MS AF Sabatine, MS TI When prognosis precedes diagnosis: putting the cart before the horse SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID ISCHEMIA-MODIFIED ALBUMIN; ACUTE CORONARY SYNDROMES; MYOCARDIAL-ISCHEMIA; EMERGENCY-DEPARTMENT; TROPONIN-I; CARDIAC ISCHEMIA; UNSTABLE ANGINA; ANGIOPLASTY; STANDARD; BINDING C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Grp, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 15 TC 3 Z9 5 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 21 PY 2005 VL 172 IS 13 BP 1697 EP 1698 DI 10.1503/cmaj.050560 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 934HY UT WOS:000229701100029 PM 15967973 ER PT J AU Gardner, DM Baldessarini, RJ Waraich, P AF Gardner, DM Baldessarini, RJ Waraich, P TI Modern antipsychotic drugs: a critical overview SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Review ID INDUCED WEIGHT-GAIN; NEUROLEPTIC MALIGNANT SYNDROME; NEW-GENERATION ANTIPSYCHOTICS; ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND; 2ND-GENERATION ANTIPSYCHOTICS; CONTROLLED-TRIALS; CONVENTIONAL ANTIPSYCHOTICS; SCHIZOAFFECTIVE DISORDER; 1ST-EPISODE PSYCHOSIS AB ConventionaL Antipsychotic Drugs, used for a half century to treat a range of major psychiatric disorders, are being replaced in clinical practice by modern "atypical" antipsychotics, including aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone among others. As a class, the newer drugs have been promoted as being broadly clinically superior, but the evidence for this is problematic. In this brief critical overview, we consider the pharmacology, therapeutic effectiveness, tolerability, adverse effects and costs of individual modern agents versus older antipsychotic drugs. Because of typically minor differences between agents in clinical effectiveness and tolerability, and because of growing concerns about potential adverse long-term health consequences of some modern agents, it is reasonable to consider both older and newer drugs for clinical use, and it is important to inform patients of relative benefits, risks and costs of specific choices. C1 Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. Dalhousie Univ, Coll Pharm, Halifax, NS B3H 3J5, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Psychopharmacol Program, McLean Div, Boston, MA 02114 USA. Univ British Columbia, Dept Psychiat, Mental Hlth Evaluat & Community Consultat Unit, Vancouver, BC, Canada. RP Gardner, DM (reprint author), Queen Elizabeth II Hlth Sci Ctr, Rm AJLB 7517,5909 Vet Mem Lane, Halifax, NS B3H 2E2, Canada. EM david.gardner@dal.ca NR 94 TC 187 Z9 196 U1 4 U2 14 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 21 PY 2005 VL 172 IS 13 BP 1703 EP 1711 DI 10.1503/cmaj.1041064 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 934HY UT WOS:000229701100032 PM 15967975 ER PT J AU Moselewski, F O'Donnell, CJ Achenbach, S Ferencik, M Massaro, J Nguyen, A Cury, RC Abbara, S Jang, IK Brady, TJ Hoffmann, U AF Moselewski, F O'Donnell, CJ Achenbach, S Ferencik, M Massaro, J Nguyen, A Cury, RC Abbara, S Jang, IK Brady, TJ Hoffmann, U TI Calcium concentration of individual coronary calcified plaques as measured by multidetector row computed tomography SO CIRCULATION LA English DT Article DE aging; atherosclerosis; calcification; physiologic; coronary disease; tomography ID ELECTRON-BEAM TOMOGRAPHY; HEART-DISEASE EVENTS; ARTERY CALCIUM; ATHEROSCLEROTIC LESIONS; MYOCARDIAL-INFARCTION; CT; QUANTIFICATION; PROGRESSION; CALCIFICATION; DEATH AB Background - Characteristics of individual calcified plaques, especially calcium concentration ( CC), may provide incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and evaluation of therapeutic intervention. In this study, therefore, we assessed the characteristics of individual calcified plaques and their relationship to other parameters derived from CT analysis of coronary calcium in a community- based cross- sectional cohort. Methods and Results - Coronary artery calcium ( CAC) was analyzed in 612 participants of the Framingham Heart Study ( third- generation and offspring cohorts) using prospectively ECG- triggered multidetector CT. We determined the CC, Agatston score, calcified volume, and mineral mass of individual calcified plaques in each subject. Heterogeneity of CC was defined as the standard deviation of CC of all individual calcified plaques in a subject. CAC was detected in 274 of 605 subjects. After excluding 57 subjects ( 21%) because of motion artifacts, we identified a total of 956 calcified coronary plaques in 217 subjects ( 74 women, 143 men; mean age, 57.1 +/- 10.8 years) with detectable CAC and no image artifacts. CC of individual calcified plaques was independent of subject age ( P = 0.76) and sex ( 197.8 +/- 74.8 versus 183.6 +/- 52.8 mg/ cm(3) for men versus women; P = 0.21). Among a subgroup of 125 subjects with multiple ( >= 3) individual calcified plaques, CC was heterogeneous within individual subjects ( mean SD of CC, 43.6 +/- 23.1 mg/ cm3). The degree of heterogeneity of CC in these subjects was independent of age ( P = 0.60), sex ( P = 0.99), and number of plaques ( P = 0.06). Conclusions - The CC of individual calcified plaques is independent of age and sex but heterogeneous within a subject, which may reflect that the pathological process of calcified plaque formation and progression is the same in men and women regardless of age. CC may have incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and the evaluation of therapeutic intervention. Further studies are warranted to confirm that individual plaque analysis is preferable to global CAC scores to evaluate progression of atherosclerosis and to assess whether individual plaque analysis may be complementary to global CAC measures to assess coronary event risk. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [N01-HC-25195] NR 33 TC 30 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 21 PY 2005 VL 111 IS 24 BP 3236 EP 3241 DI 10.1161/CIRCULATIONAHA.104.489781 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 937MX UT WOS:000229930200010 PM 15956133 ER PT J AU Hogan, PG Li, HM AF Hogan, PG Li, HM TI Calcineurin SO CURRENT BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hogan, PG (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM hogan@cbr.med.harvard.edu NR 2 TC 15 Z9 15 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 21 PY 2005 VL 15 IS 12 BP R442 EP R443 DI 10.1016/j.cub.2005.06.006 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 941BH UT WOS:000230189100008 PM 15964258 ER PT J AU Narula, J Finn, AV DeMaria, AN AF Narula, J Finn, AV DeMaria, AN TI Picking plaques that pop... SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID INTRAVASCULAR ULTRASOUND; VULNERABLE PLAQUE; CORONARY PLAQUE; ATHEROSCLEROTIC LESIONS; IN-VIVO; ATHEROMA; ECHOCARDIOGRAPHY; ELASTOGRAPHY; COMPONENTS; MORPHOLOGY C1 UCI, Med Ctr, Orange, CA 92868 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. RP Narula, J (reprint author), UCI, Med Ctr, 101 City Dr,Bldg 53,Rt 81, Orange, CA 92868 USA. EM narula@uci.edu NR 33 TC 29 Z9 30 U1 0 U2 4 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 JUN 21 PY 2005 VL 45 IS 12 BP 1970 EP 1973 DI 10.1016/j.jacc.2005.03.034 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 936IK UT WOS:000229848500009 PM 15963394 ER PT J AU Mozaffarian, D Bryson, CL Lemaitre, RN Burke, GL Siscovick, DS AF Mozaffarian, D Bryson, CL Lemaitre, RN Burke, GL Siscovick, DS TI Fish intake and risk of incident heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 03-06, 2004 CL San Francisco, CA SP Amer Heart Assoc ID POLYUNSATURATED FATTY-ACIDS; CARDIOVASCULAR HEALTH; CONTRACTILE FUNCTION; SYSTOLIC FUNCTION; BLOOD-PRESSURE; TRAINED RATS; OIL; CONSUMPTION; OMEGA-3-FATTY-ACIDS; MODULATION AB OBJECTIVES Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF). BACKGROUND The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown. METHODS Among 4,738 adults age >= 65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated. RESULTS During 12 years' follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to 0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% Cl = 0.52 to 0.91), and 32% lower risk with intake >= 5 times/week (HR = 0.68, 95% CI = 0.45 to 1.03), compared with intake < 1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37% lower risk in the highest quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest. CONCLUSIONS Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted. (c) 2005 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 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 [N01 HC 85079, K08 HL 075628, N01 HC 15103, N01 HC 35129, N01 HC 85086] NR 34 TC 149 Z9 152 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 21 PY 2005 VL 45 IS 12 BP 2015 EP 2021 DI 10.1016/j.jacc.2005.03.038 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 936IK UT WOS:000229848500018 PM 15963403 ER PT J AU Trofimov, A Rietzel, E Lu, HM Martin, B Jiang, S Chen, GTY Bortfeld, T AF Trofimov, A Rietzel, E Lu, HM Martin, B Jiang, S Chen, GTY Bortfeld, T TI Temporo-spatial IMRT optimization: concepts, implementation and initial results SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INCORPORATING ORGAN MOTION; FLUENCE-CONVOLUTION METHOD; 3D DOSE CALCULATIONS; RESPIRATORY MOTION; RADIATION-THERAPY; TUMOR MOTION; MONTE-CARLO; LUNG; DISTRIBUTIONS; RADIOTHERAPY AB With the recent availability of 4D-CT, the accuracy of information on internal organ motion during respiration has improved significantly. We investigate the utility of organ motion information in IMRT treatment planning, using an in-house prototype optimization system. Four approaches are compared: (1) planning with optimized margins, based on motion information; (2) the,motion kernel' approach, in which a more accurate description of the dose deposit from a pencil beam to a moving target is achieved either through time-weighted averaging of influence matrices, calculated for different instances of anatomy (subsets of 4D-CT data, corresponding to various phases of motion) or through convolution of the pencil beam kernel with the probability density function describing the target motion; (3) optimal gating, or tracking with beam intensity maps optimized independently for each instance of anatomy; and (4) optimal tracking with beam intensity maps optimized simultaneously for all instances of anatomy. The optimization is based on a gradient technique and can handle both physical (dose-volume) and equivalent uniform dose constraints. Optimization requires voxel mapping from phase to phase in order to score the dose in individual voxels as they move. The results show that, compared to the other approaches, margin expansion has a significant disadvantage by substantially increasing the integral dose to patient. While gating or tracking result in the best dose conformation to the target, the former elongates treatment time, and the latter significantly complicates the delivery procedure. The,motion kernel' approach does not provide a dosimetric advantage, compared to optimal tracking or gating, but might lead to more efficient delivery. A combination of gating with the 'motion kernel' or margin expansion approach will increase the duty cycle and may provide one with the most efficient solution, in terms of complexity of the delivery procedure and dose conformality to the target. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM atrofimov@partners.org FU NCI NIH HHS [5-P01-CA21239-25] NR 39 TC 96 Z9 96 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2005 VL 50 IS 12 BP 2779 EP 2798 DI 10.1088/0031-9155/50/12/004 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 948IU UT WOS:000230710200004 PM 15930602 ER PT J AU Shiotani, A Ishi, H Uedo, N Kumamoto, M Nakae, Y Ishiguro, S Tatsuta, M Graham, DY AF Shiotani, A Ishi, H Uedo, N Kumamoto, M Nakae, Y Ishiguro, S Tatsuta, M Graham, DY TI Histologic and serum risk markers for noncardia early gastric cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE corpus dominant gastritis; early gastric cancer; gastrin 17; intestinal metaplasia; pepsinogen I ID HELICOBACTER-PYLORI INFECTION; INTESTINAL METAPLASIA; ATROPHIC GASTRITIS; PEPSINOGEN-I; ENDOSCOPIC DIAGNOSIS; STOMACH; CARCINOGENESIS; CARCINOMA; DYSPLASIA; SEQUENCE AB Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori-positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI) 1.6-7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3-52.6) (p < 0.001)). The best cut-off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 > 60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow-up is warranted for patients with IM found at the greater curvature of the corpus. © 2005 Wiley-Liss, Inc. C1 Wakayama Univ, Hlth Adm Ctr, Wakayama 6408510, Japan. Osaka Med Ctr Canc & Cardiovasc Dis, Dept Gastrointestinal Oncol, Osaka, Japan. VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Shiotani, A (reprint author), Wakayama Univ, Hlth Adm Ctr, 930 Sakaedani, Wakayama 6408510, Japan. EM shiotani@center.wakayama-u.ac.jp NR 32 TC 49 Z9 52 U1 0 U2 1 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 JUN 20 PY 2005 VL 115 IS 3 BP 463 EP 469 DI 10.1002/ijc.20852 PG 7 WC Oncology SC Oncology GA 925BD UT WOS:000229025600018 PM 15688378 ER PT J AU Pappo, AS Devidas, M Jenkins, J Rao, B Marcus, R Thomas, P Gebhardt, M Pratt, C Grier, HE AF Pappo, AS Devidas, M Jenkins, J Rao, B Marcus, R Thomas, P Gebhardt, M Pratt, C Grier, HE TI Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: A pediatric oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol ID HIGH-DOSE IFOSFAMIDE; EUROPEAN-ORGANIZATION; PROGNOSTIC-FACTORS; PLUS DOXORUBICIN; SYNOVIAL SARCOMA; FINAL REPORT; BONE; CHEMOTHERAPY; SURVIVAL; MESNA AB Purpose To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. Patients and Methods Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mu g/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. Results The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36 %); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41 % (95 % Cl, 25.7 % to 56.7 %). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59 % +/- 8.2 % and 43.6 % +/- 7 %, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. Conclusion The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients. C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Tampa Childrens Hosp, Tampa, FL USA. Pediat Oncol Grp, Stat Off, Gainesville, FL USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pappo, AS (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM alberto.pappo@sickkids.ca NR 31 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2005 VL 23 IS 18 BP 4031 EP 4038 DI 10.1200/JCO.2005.03.209 PG 8 WC Oncology SC Oncology GA 936WR UT WOS:000229886700006 PM 15767644 ER PT J AU Feldman, EJ Brandwein, J Stone, R Kalaycio, M Moore, J O'Connor, J Wedel, N Roboz, GJ Miller, C Chopra, R Jurcic, JC Brown, R Ehmann, WC Schulman, P Frankel, SR De Angelo, D Scheinberg, D AF Feldman, EJ Brandwein, J Stone, R Kalaycio, M Moore, J O'Connor, J Wedel, N Roboz, GJ Miller, C Chopra, R Jurcic, JC Brown, R Ehmann, WC Schulman, P Frankel, SR De Angelo, D Scheinberg, D TI Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID ACUTE MYELOGENOUS LEUKEMIA; GEMTUZUMAB OZOGAMICIN; SALVAGE THERAPY; M195 ANTI-CD33; CELLS; CD33; EXPRESSION; INDUCTION; RELAPSE; HUM195 AB Purpose Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy. alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML). Patients and Methods Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m(2), etoposide 80 mg/m(2), and cytarabine 1 g/m(2) daily for 6 days (MEC) in combination with lintuzumab 12 mg/m(2), or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity. Results A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36 % v 28 % in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion-related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy. Conclusion The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/ relapsed AML. C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Christie Hosp, Manchester, Lancs, England. Washington Univ, St Louis, MO USA. MS Hershey Med Ctr, Hershey, PA USA. N Shore Univ Hosp, Manhasset, NY USA. Prot Design Labs, Fremont, CA USA. RP Feldman, EJ (reprint author), Cornell Univ, Weill Med Coll, 525 E 68th St, New York, NY 10021 USA. EM ejf2001@med.cornell.edu NR 28 TC 116 Z9 121 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2005 VL 23 IS 18 BP 4110 EP 4116 DI 10.1200/JCO.2005.09.133 PG 7 WC Oncology SC Oncology GA 936WR UT WOS:000229886700015 PM 15961759 ER PT J AU Iwasaki, H Mizuno, S Mayfield, R Shigematsu, H Arinobu, Y Seed, B Gurish, MF Takatsu, K Akashi, K AF Iwasaki, H Mizuno, S Mayfield, R Shigematsu, H Arinobu, Y Seed, B Gurish, MF Takatsu, K Akashi, K TI Identification of eosinophil lineage - committed progenitors in the murine bone marrow SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC PROGENITORS; TRANSGENIC MICE; MONOCLONAL-ANTIBODY; INTERLEUKIN-5 IL-5; COLONIES; GENE; DIFFERENTIATION; TRANSCRIPTION; GATA-1; DEFICIENCY AB Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/ monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5R alpha(+)CD34(+)c- Kit(lo) phenotype. Normal bone marrow cells also contained IL-5R alpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5R alpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5R alpha(+) GMPs displayed normal neutrophil/ monocyte differentiation in the presence of IL-5 alone. Thus, IL-5R alpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Immunol, Tokyo 1088639, Japan. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM koichi_akashi@dfci.harvard.edu FU NIAID NIH HHS [U19 AI031599, AI 031599, P01 AI031599]; NIDDK NIH HHS [DK 050654, P01 DK050654] NR 30 TC 103 Z9 109 U1 0 U2 3 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 JUN 20 PY 2005 VL 201 IS 12 BP 1891 EP 1897 DI 10.1084/jem.20050548 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 937MZ UT WOS:000229930400005 PM 15955840 ER PT J AU Zhu, PC Sang, YY Xu, HB Zhao, J Xu, RN Sun, YB Xu, TH Wang, XL Chen, LF Feng, HP Li, CB Zhao, S AF Zhu, PC Sang, YY Xu, HB Zhao, J Xu, RN Sun, YB Xu, TH Wang, XL Chen, LF Feng, HP Li, CB Zhao, S TI ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ADAM22; 14-3-3; yeast two-hybrid; cell adhesion; cell spreading ID NECROSIS-FACTOR-ALPHA; SPERM-EGG FUSION; METALLOPROTEINASE-DISINTEGRIN; MATRIX INTERACTIONS; IN-VITRO; PROTEINS; INTEGRIN; IDENTIFICATION; BINDING; FAMILY AB Cellular adhesion plays important roles in a variety of biological processes. The ADAM family contains disintegrin-like and metalloproteinase-like domains which potentially have cell adhesion and protease activities. Recent studies suggest that the interaction between 14-3-3 zeta and ADAM22cyt can regulate cell adhesion and spreading, therefore it has a potential role in neural development and function. 14-3-3 family has seven highly conserved members that regulate various cellular functions. Using yeast two-hybrid method, we identified that ADAM22cyt bound some other 14-3-3 family members. The interaction was further confirmed by in vitro protein pull-down assay and co-immunoprecipitation. We also found that the overexpression of exogenous ADAM22 in HEK293 cells could significantly enhance cell adhesion and spreading, compared with the truncated ADAM22 lack of 14-3-3 binding motifs. These results strongly demonstrated a functional role for ADAM22/14-3-3 in cell adhesion and spreading. (c) 2005 Elsevier Inc. All rights reserved. C1 Fudan Univ, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. Harvard Univ, Sch Med, Dept Pediat, CBR Biomed Res Ctr, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Med, Miami, FL 33101 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, Dept Biomed Sci, North Grafton, MA 01536 USA. RP Zhu, PC (reprint author), Fudan Univ, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. EM pzhu@cbr.med.harvard.edu; syzhao@fudan.edu.cn FU NIAMS NIH HHS [AR 26599] NR 41 TC 15 Z9 17 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 17 PY 2005 VL 331 IS 4 BP 938 EP 946 DI 10.1016/j.bbrc.2005.03.229 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 927XS UT WOS:000229234500008 PM 15882968 ER PT J AU Westbrook, TF Martin, ES Schlabach, MR Leng, YM Liang, AC Feng, B Zhao, JJ Roberts, TM Mandel, G Hannon, GJ DePinho, RA Chin, L Elledge, SJ AF Westbrook, TF Martin, ES Schlabach, MR Leng, YM Liang, AC Feng, B Zhao, JJ Roberts, TM Mandel, G Hannon, GJ DePinho, RA Chin, L Elledge, SJ TI A genetic screen for candidate tumor suppressors identifies REST SO CELL LA English DT Article ID MAMMARY EPITHELIAL-CELLS; TGF-BETA; HUMAN CANCER; TRANSFORMATION; RAS; EXPRESSION; PATHWAY; ADENOCARCINOMA; PROLIFERATION; REQUIREMENTS AB Tumorigenesis is a multistep process characterized by a myriad of genetic and epigenetic alterations. Identifying the causal perturbations that confer malignant transformation is a central goal in cancer biology. Here we report an RNAi-based genetic screen for genes that suppress transformation of human mammary epithelial cells. We identified genes previously implicated in proliferative control and epithelial cell function including two established tumor suppressors, TGFBR2 and PTEN. In addition, we uncovered a previously unrecognized tumor suppressor role for REST/ NRSF, a transcriptional repressor of neuronal gene expression. Array-CGH analysis identified REST as a frequent target of deletion in colorectal cancer. Furthermore, we detect a frameshift mutation of the REST gene in colorectal cancer cells that encodes a dominantly acting truncation capable of transforming epithelial cells. Cells lacking REST exhibit increased PI(3)K signaling and are dependent upon this pathway for their transformed phenotype. These results implicate REST as a human tumor suppressor and provide a novel approach to identifying candidate genes that suppress the development of human cancer. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Partners Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. SUNY Stony Brook, Howard Hughes Med Inst, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Partners Ctr Genet & Genom, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [5 P01 CA89021-04, 5 P50 CA090381-03, 5T32CA09361, R01CA93947, R01CA99041, U01 CA084313] NR 45 TC 332 Z9 344 U1 2 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 17 PY 2005 VL 121 IS 6 BP 837 EP 848 DI 10.1016/j.cell.2005.03.033 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 938NX UT WOS:000230011200007 PM 15960972 ER PT J AU Pennathur, S Ido, Y Heller, JI Byun, J Danda, R Pergola, P Willliamson, JR Heinecke, JW AF Pennathur, S Ido, Y Heller, JI Byun, J Danda, R Pergola, P Willliamson, JR Heinecke, JW TI Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species - A potential pathway for oxidative damage of retinal proteins in diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRIC QUANTIFICATION; AUTOXIDATIVE GLYCOSYLATION; LIPID-PEROXIDATION; VASCULAR-DISEASE; MICROVASCULAR COMPLICATIONS; GLUCOSE AUTOXIDATION; NITRATIVE STRESS; ORTHO-TYROSINE; SKIN COLLAGEN AB The pattern of oxidized amino acids in aortic proteins of nonhuman primates suggests that a species resembling hydroxyl radical damages proteins when blood glucose levels are high. However, recent studies argue strongly against a generalized increase in diabetic oxidative stress, which might instead be confined to the vascular wall. Here, we describe a pathway for glucose-stimulated protein oxidation and provide evidence of its complicity in diabetic microvascular disease. Low density lipoprotein incubated with pathophysiological concentrations of glucose became selectively enriched in ortho-tyrosine and meta-tyrosine, implicating a hydroxyl radical-like species in protein damage. Model system studies demonstrated that the reaction pathway requires both a reactive carbonyl group and a polyunsaturated fatty acid, involves lipid peroxidation, and is blocked by the carbonyl scavenger aminoguanidine. To explore the physiological relevance of the pathway, we used mass spectrometry and high pressure liquid chromatography to quantify oxidation products in control and hyperglycemic rats. Hyperglycemia raised levels of ortho-tyrosine, meta-tyrosine, and oxygenated lipids in the retina, a tissue rich in polyunsaturated fatty acids. Rats that received aminoguanidine did not show this increase in protein and lipid oxidation. In contrast, rats with diet-induced hyperlipidemia in the absence of hyperglycemia failed to exhibit increased protein and lipid oxidation products in the retina. Our observations suggest that generation of a hydroxyl radical-like species by a carbonyl/polyunsaturated fatty acid pathway might promote localized oxidative stress in tissues vulnerable to diabetic damage. This raises the possibility that antioxidant therapies that specifically inhibit the pathway might delay the vascular complications of diabetes. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Rush Univ, Dept Pathol, Chicago, IL 60612 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Heinecke, JW (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. EM heinecke@u.washington.edu FU NEI NIH HHS [EY06600]; NHLBI NIH HHS [HL39934]; NIA NIH HHS [AG021191]; NIDDK NIH HHS [DK20579, DK02456]; NIEHS NIH HHS [P30ES07033] NR 61 TC 43 Z9 43 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 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 22706 EP 22714 DI 10.1074/jbc.M500839200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800020 PM 15855169 ER PT J AU Qiao, ZS Kim, MK Reinhold, B Montefiori, D Wang, JH Reinherz, EL AF Qiao, ZS Kim, MK Reinhold, B Montefiori, D Wang, JH Reinherz, EL TI Design, expression, and immunogenicity of a soluble HIV trimeric envelope fragment adopting a prefusion gp41 configuration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL MEMBRANE-FUSION; TYPE-1 GP41; TRANSMEMBRANE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; POTENT INHIBITORS; ATOMIC-STRUCTURE; FAB FRAGMENTS; GP120 AB The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env) is comprised of non-covalently associated gp120/gp41 subunits that form trimeric spikes on the virion surface. Upon binding to host cells, Env undergoes a series of structural transitions, leading to gp41 rearrangement necessary for fusion of viral and host membranes. Until now, the prefusion state of gp41 ectodomain (e-gp41) has eluded molecular and structural analysis, and thus assessment of the potential of such an e-gp41 conformer to elicit neutralizing antibodies has not been possible. Considering the importance of gp120 amino (C1) and carboxyl (C5) segments in the association with e-gp41, we hypothesize that these regions are sufficient to maintain e- gp41 in a prefusion state. Based on the available gp120 atomic structure, we designed several truncated gp140 variants by including the C1 and C5 regions of gp120 in a gp41 ectodomain fragment. After iterative cycles of protein design, expression and characterization, we obtained a variant truncated at Lys(665) that stably folds as an elongated trimer under physiologic conditions. Several independent biochemical/biophysical analyses strongly suggest that this mini-Env adopts a prefusion e- gp41 configuration that is strikingly distinct from the postfusion trimer-of-hairpin structure. Interestingly, this prefusion mini-Env, lacking the fragment containing the 2F5/4E10 neutralizing monoclonal antibody binding sites, displays no detectable HIV-neutralizing epitopes when employed as an immunogen in rabbits. The result of this immunogenicity study has important implications for HIV-1 vaccine design efforts. Moreover, this engineered mini-Env protein should facilitate three-dimensional structural studies of the prefusion e- gp41 and serve to guide future attempts at pharmacologic and immunologic intervention of HIV-1. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI43649] NR 51 TC 19 Z9 19 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 23138 EP 23146 DI 10.1074/jbc.M414515200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800071 PM 15833740 ER PT J AU Kubota, K Lee, DH Tsuchiya, M Young, CS Everett, ET Martinez-Mier, EA Snead, ML Nguyen, L Urano, F Bartlett, JD AF Kubota, K Lee, DH Tsuchiya, M Young, CS Everett, ET Martinez-Mier, EA Snead, ML Nguyen, L Urano, F Bartlett, JD TI Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; RADIATION-INDUCED APOPTOSIS; MAXILLARY CENTRAL INCISORS; EPITHELIAL LUNG-CELLS; MESSENGER-RNA; TRANSCRIPTION FACTOR; TRANSLATIONAL CONTROL; DNA FRAGMENTATION; GENE-EXPRESSION; CRITICAL PERIOD AB mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45 alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Tohoku Univ, Grad Sch Dent, Div Aging & Geriatr Dent, Sendai, Miyagi 9808578, Japan. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Indiana Univ, Sch Med & Dent, Oral Hlth Res Inst, Dept Prevent & Community Dent, Indianapolis, IN 46202 USA. Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01655 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM jbartlett@forsyth.org OI Tsuchiya, Masahiro/0000-0002-7000-4547 FU NCI NIH HHS [CO6RR11244]; NIDCR NIH HHS [DE13237, DE14084, P01 DE013237, R01 DE014084] NR 64 TC 87 Z9 104 U1 1 U2 11 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 JUN 17 PY 2005 VL 280 IS 24 BP 23194 EP 23202 DI 10.1074/jbc.M503288200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800077 PM 15849362 ER PT J AU Kim, DY Ingano, LAM Carey, BW Pettingell, WH Kovacs, DM AF Kim, DY Ingano, LAM Carey, BW Pettingell, WH Kovacs, DM TI Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta 2-subunit regulates cell adhesion and migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE; INTRACELLULAR DOMAIN; BETA-SUBUNITS; INTRAMEMBRANE CLEAVAGE; NEUROBLASTOMA-CELLS; ALZHEIMERS-DISEASE; ERBB-4 RECEPTOR; MESSENGER-RNA; NOTCH AB The voltage-gated sodium channel beta 2-subunit (beta 2) is a member of the IgCAM superfamily and serves as both an adhesion molecule and an auxiliary subunit of the voltage-gated sodium channel. Here we found that beta 2 undergoes ectodomain shedding followed by presenilin (PS)-dependent gamma-secretase- mediated cleavage. 12-O-Tetradecanoylphorbol13- acetate treatment or expression of an alpha-secretase enzyme, ADAM10, resulted in ectodomain cleavage of beta 2 in Chinese hamster ovary cells. Subsequent cleavage of the remaining 15-kDa C-terminal fragment (beta 2-CTF) was independently inhibited by three specific gamma-secretase inhibitors, expression of the dominant negative form of PS1, and in PS1/ PS2 knock-out cells. gamma-Secretase inhibitor treatment also increased endogenous beta 2-CTF levels in neuroblastoma cells and mouse primary neuronal cultures. In a cell-free gamma-secretase assay, we detected gamma-secretase activity-dependent generation of a 12 kDa beta 2 intracellular domain (ICD), which was loosely associated with the membrane fraction. To assess the functional role of beta 2 processing by gamma-secretase, we tested whether N-[N-(3,5- difluorophenylacetyl-L- alanyl)]-S-phenylglycine t-butylester (DAPT), a specific beta-secretase inhibitor, would alter beta 2-mediated cell adhesion and migration. We found that DAPT inhibited cell-cell aggregation and migration in a wound healing assay carried out with Chinese hamster ovary cells expressing beta 2. DAPT also reduced migration of neuroblastoma cells in a modified Boyden chamber assay. Since DAPT treatment resulted in increased beta 2-CTF levels, we also tested whether beta 2-CTFs or beta 2-ICDs would directly affect cell migration by overexpressing recombinant proteins. Interestingly, elevated levels of beta 2-CTFs, but not ICDs, also blocked cell migration by 81 to 93%. Together, our findings show for the first time that beta 2 is a PS/gamma-secretase substrate and gamma-secretase mediated cleavage of beta 2-CTF is required for cell-cell adhesion and migration of beta 2-expressing cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Neurobiol Dis Lab, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Neurobiol Dis Lab, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu NR 63 TC 97 Z9 101 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 23251 EP 23261 DI 10.1074/jbc.M412938200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800083 PM 15833746 ER PT J AU Mulky, A Sarafianos, SG Jia, YJ Arnold, E Kappes, JC AF Mulky, A Sarafianos, SG Jia, YJ Arnold, E Kappes, JC TI Identification of amino acid residues in the human immunodeficiency virus type-1 reverse transcriptase tryptophan-repeat motif that are required for subunit interaction using infectious virions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE reverse transcriptase; subunit-specific; Trp-motif; dimerization; NNRTI ID POLYMERASE DOMAIN; PRIMER GRIP; H ACTIVITY; HIV-1; DIMERIZATION; INHIBITOR; MUTAGENESIS; INTERFACE; PROTEIN; DESTABILIZATION AB The human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) functions as a heterodimer (p51/p66), which makes disruption of subunit interactions a possible target for antiviral drug design. Our understanding of subunit interface interactions has been limited by the lack of virus-based approaches for studying the heterodimer. Therefore, we developed a novel subunit-specific mutagenesis approach that enables precise molecular analysis of the heterodimer in the context of infectious HIV-1 particles. Here, we analyzed the contributions of amino acid residues comprising the Trp-motif to RT subunit interaction and function. Our results reveal important inter- and intra-subunit interactions of residues in the Trp-motif. A tryptophan cluster in p51. (W398, W402, W406, W414), proximal to the interface, was found to be important for p51/p66 interaction and stability. At the dimer interface, residues W401, Y405 and N363 in p51 and W410 in p66 mediate inter-subunit interactions. The W401 residue is critical for RT dimerization, exerting distinct effects in p51 and p66. Our analysis of the RT heterodimerization enhancing nonnucleoside RT inhibitor (NNRTI), efavirenz, indicates that the effects of drugs on RT dimer stability can be examined in human cells. Thus, we provide the first description of subunit-specific molecular interactions that affect RT heterodimer function and virus infection in vivo. Moreover, with heightened interest in novel RT inhibitors that affect dimerization, we demonstrate the ability to assess the effects of RT inhibitors on subunit interactions in a physiologically relevant context. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. EM kappesjc@uab.edu OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [AI47714, P10-AI-27767]; NIDDK NIH HHS [R24 DK-64400] NR 46 TC 26 Z9 26 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 JUN 17 PY 2005 VL 349 IS 4 BP 673 EP 684 DI 10.1016/j.jmb.2005.03.057 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 933PQ UT WOS:000229645800001 PM 15893326 ER PT J AU Sun, T Patoine, C Abu-Khalil, A Visvader, J Sum, E Cherry, TJ Orkin, SH Geschwind, DH Walsh, CA AF Sun, T Patoine, C Abu-Khalil, A Visvader, J Sum, E Cherry, TJ Orkin, SH Geschwind, DH Walsh, CA TI Early asymmetry of gene transcription in embryonic human left and right cerebral cortex SO SCIENCE LA English DT Article ID HUMAN-BRAIN; HANDEDNESS; SPEECH; LATERALITY; EVOLUTION; MICE AB The human left and right cerebral hemispheres are anatomically and functionally asymmetric. To test whether human cortical asymmetry has a molecular basis, we studied gene expression levels between the left and right embryonic hemispheres using serial analysis of gene expression (SAGE). We identified and verified 27 differentialty expressed genes, which suggests that human cortical asymmetry is accompanied by early, marked transcriptional asymmetries. LMO4 is consistently more highly expressed in the right perisylvian human cerebral cortex than in the left and is essential for cortical development in mice, suggesting that human left-right specialization reflects asymmetric cortical development at early stages. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Neurol, Program Neurogenet, Sch Med, Los Angeles, CA 90095 USA. Walter & Eliza Hall Inst Med Res, Victorian Breast Canc Res Consortium Lab, Melbourne, Vic 3050, Australia. Boston Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Walsh, CA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, New Res Bldg Room 0266,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwalsh@bidmc.harvard.edu FU Howard Hughes Medical Institute; NIMH NIH HHS [R37 MH060233, MH60233, R01 MH060233, R56 MH060233]; NINDS NIH HHS [R01 NS035129, R01 NS035129-03, R01 R37 NS35129, R37 NS035129, R37 NS035129-05] NR 23 TC 186 Z9 189 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 17 PY 2005 VL 308 IS 5729 BP 1794 EP 1798 DI 10.1126/science.1110324 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 937LY UT WOS:000229926800057 PM 15894532 ER PT J AU Fre, S Huyghe, M Mourikis, P Robine, S Louvard, D Artavanis-Tsakonas, S AF Fre, S Huyghe, M Mourikis, P Robine, S Louvard, D Artavanis-Tsakonas, S TI Notch signals control the fate of immature progenitor cells in the intestine SO NATURE LA English DT Article ID VILLIN GENE; EPITHELIAL-CELLS; STEM-CELLS; EXPRESSION; DIFFERENTIATION; MICE; PROLIFERATION; NEUROGENIN3; MATH1; HES5 AB The Notch signalling pathway plays a crucial role in specifying cellular fates in metazoan development by regulating communication between adjacent cells(1,2). Correlative studies suggested an involvement of Notch in intestinal development. Here, by modulating Notch activity in the mouse intestine, we directly implicate Notch signals in intestinal cell lineage specification. We also show that Notch activation is capable of amplifying the intestinal progenitor pool while inhibiting cell differentiation. We conclude that Notch activity is required for the maintenance of proliferating crypt cells in the intestinal epithelium. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Cell Biol, Charlestown, MA 02129 USA. Inst Curie, CNRS, F-75231 Paris, France. Univ Paris 11, Fac Sci Orsay, F-91405 Orsay, France. Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Cell Biol, Charlestown, MA 02129 USA. EM tsakonas@helix.mgh.harvard.edu RI Fre, Silvia/C-7540-2017 OI Fre, Silvia/0000-0002-7209-7636 NR 30 TC 471 Z9 486 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 16 PY 2005 VL 435 IS 7044 BP 964 EP 968 DI 10.1038/nature03589 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935RN UT WOS:000229799700051 PM 15959516 ER PT J AU Sipkins, DA Wei, XB Wu, JW Runnels, JM Cote, D Means, TK Luster, AD Scadden, DT Lin, CP AF Sipkins, DA Wei, XB Wu, JW Runnels, JM Cote, D Means, TK Luster, AD Scadden, DT Lin, CP TI In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment SO NATURE LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; STEM-CELLS; ADHESION MOLECULES; NOD/SCID MICE; CANCER-CELLS; PRECURSOR-B; EXPRESSION; LEUKEMIA; MICROVESSELS; VOLUNTEERS AB The organization of cellular niches is known to have a key role in regulating normal stem cell differentiation and regeneration, but relatively little is known about the architecture of microenvironments that support malignant metastasis(1,2). Using dynamic in vivo confocal imaging, here we show that murine bone marrow contains unique anatomic regions defined by specialized endothelium. This vasculature expresses the adhesion molecule E-selectin and the chemoattractant stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that influence the homing of a variety of tumour cell lines. Disruption of the interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6 cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further studies revealed that circulating leukaemic cells can engraft around these vessels, suggesting that this molecularly distinct vasculature demarcates a microenvironment for early metastatic tumour spread in bone marrow. Finally, purified haematopoietic stem/progenitor cells and lymphocytes also localize to the same microdomains, indicating that this vasculature might also function in benign states to demarcate specific portals for the entry of cells into the marrow space. Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM dsipkins1@partners.org; lin@helix.mgh.harvard.edu RI Cote, Daniel/D-5185-2011 FU NCI NIH HHS [T32 CA071345, P50 CA086355]; NEI NIH HHS [R01 EY014106]; NIBIB NIH HHS [R01 EB000664] NR 30 TC 444 Z9 464 U1 5 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 16 PY 2005 VL 435 IS 7044 BP 969 EP 973 DI 10.1038/nature03703 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935RN UT WOS:000229799700052 PM 15959517 ER PT J AU Richardson, PG Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D San-Miguel, JF Blade, J Boccadoro, M Cavenagh, J Dalton, WS Boral, AL Esseltine, DL Porter, JB Schenkein, D Anderson, KC AF Richardson, PG Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D San-Miguel, JF Blade, J Boccadoro, M Cavenagh, J Dalton, WS Boral, AL Esseltine, DL Porter, JB Schenkein, D Anderson, KC CA APEX Investigators TI Bortezomib or high-dose dexamethasone for relapsed multiple myeloma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROTEASOME INHIBITOR PS-341; COOPERATIVE-ONCOLOGY-GROUP; RANDOMIZED PHASE-III; REFRACTORY MYELOMA; THALIDOMIDE; THERAPY; VAD; CHEMOTHERAPY; VINCRISTINE; RESISTANT AB BACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression. RESULTS: Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone. CONCLUSIONS: Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. New York Presbyterian Hosp, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Univ Klinikum Heidelberg, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Hosp Univ Salamanca, Salamanca, Spain. Inst Invest Biomed Agusti Pi & Sunyer, Barcelona, Spain. Univ Turin, Turin, Italy. St Bartholomews Hosp, London, England. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 40 TC 1515 Z9 1574 U1 7 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 JUN 16 PY 2005 VL 352 IS 24 BP 2487 EP 2498 DI 10.1056/NEJMoa043445 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 935RH UT WOS:000229798900004 PM 15958804 ER PT J AU Muto, MG O'Neill, MJ Oliva, E Harris, NL Schiff, I Scully, RE AF Muto, MG O'Neill, MJ Oliva, E Harris, NL Schiff, I Scully, RE TI A 45-year-old woman with a painful mass in the abdomen - Endometriosis associated with a surgical scar. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CLEAR-CELL-CARCINOMA; EXTRAPELVIC ENDOMETRIOSIS; ABDOMINAL-WALL; MALIGNANCY; DIAGNOSIS; OVARIAN; CANCER C1 Dana Farber Canc Inst, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet, Boston, MA USA. Harvard Univ, Sch Med, Dept Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Dept Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Muto, MG (reprint author), Dana Farber Canc Inst, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02115 USA. NR 33 TC 7 Z9 7 U1 0 U2 1 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 JUN 16 PY 2005 VL 352 IS 24 BP 2535 EP 2542 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 935RH UT WOS:000229798900011 PM 15958810 ER PT J AU Huehnergarth, KV Mozaffarian, D Sullivan, MD Crane, BA Wilkinson, CW Lawler, RL McDonald, GB Fishbein, DP Levy, WC AF Huehnergarth, KV Mozaffarian, D Sullivan, MD Crane, BA Wilkinson, CW Lawler, RL McDonald, GB Fishbein, DP Levy, WC TI Usefulness of relative lymphocyte count as an independent predictor of death/urgent transplant in heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID T-LYMPHOCYTES; ENDOTOXIN; APOPTOSIS; ACTIVATION AB The usefulness of low relative lymphocyte count as an independent predictor of death/urgent transplant in patients with heart failure (HF) and the association between low relative lymphocyte count and neurohormone and cytokine activation were investigated. Relative lymphocyte count, clinical variables, neurohormones, and cytokines were measured in 129 outpatients with HF. Follow-up extended to a mean of 3.0 +/- 1.2 years for death/urgent transplant. Low relative lymphocyte count was independently associated with a 3.4-fold increased risk of death/urgent transplant. Relative lymphocyte count was positively associated with hemoglobin and inversely associated with age, jugular venous pressure, creatinine, leukocyte count, and soluble tumor necrosis factor receptor-1. There was only a borderline inverse association with cortisol levels during evening hours. (c) 2005 by Excerpta Medica Inc. C1 Univ Washington, Dept Internal Med, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Div Psychiat, Seattle, WA USA. Channing Labs, Boston, MA USA. Brigham & Womens Hosp, Harvard Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci & Clin Res, Seattle, WA USA. RP Huehnergarth, KV (reprint author), Univ Washington, Dept Internal Med, Div Cardiol, Box 356422,1959 NE Pacific St, Seattle, WA 98195 USA. EM levywc@u.washington.edu RI Mozaffarian, Dariush/B-2276-2008 FU NCI NIH HHS [CA18029]; NCRR NIH HHS [M01-RR-0037] NR 16 TC 33 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2005 VL 95 IS 12 BP 1492 EP 1495 DI 10.1016/j.amjcard.2005.02.022 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 937VB UT WOS:000229952900023 PM 15950581 ER PT J AU Rich, DQ Schwartz, J Mittleman, MA Link, M Luttmann-Gibson, H Catalano, PJ Speizer, FE Dockery, DW AF Rich, DQ Schwartz, J Mittleman, MA Link, M Luttmann-Gibson, H Catalano, PJ Speizer, FE Dockery, DW TI Association of short-term ambient air pollution concentrations and ventricular arrhythmias SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE air pollution; arrhythmias; heart arrest; tachycardia; ventricular; ventricular fibrillation ID CASE-CROSSOVER ANALYSIS; HEART-RATE-VARIABILITY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; TRIGGERING MYOCARDIAL-INFARCTION; HOSPITAL ADMISSIONS; DAILY MORTALITY; ENVIRONMENTAL EXPOSURE; CARDIOVASCULAR-DISEASE; CARDIAC-ARRHYTHMIA; SUDDEN-DEATH AB The authors evaluated the association between ventricular arrhythmias detected by implantable cardioverter defibrillators and ambient air pollution concentrations in the hours immediately before the arrhythmia. Patients given implantable cardioverter defibrillators at the New England Medical Center in Boston, Massachusetts, between mid-1995 and 1999 who lived within 40 km of a central monitoring site (n = 203) were followed until July 2002. The authors used a case-crossover design to study the association between ambient air pollution and up to 798 confirmed ventricular arrhythmias among 84 subjects. The authors found that interquartile range increases in 24-hour moving average particulate matter less than 2.5 mu m in aerodynamic diameter and ozone were associated with 19% and 21% increased risks of ventricular arrhythmia, respectively. For each, there was evidence of a linear exposure response, and the associations appeared independent. These associations were stronger than associations with mean concentrations on the same calendar day and previous calendar days. The authors did not find associations with pollutant concentrations less than 24 hours before the arrhythmia. Cases with a prior ventricular arrhythmia within 72 hours had greater risk associated with air pollutants than did cases without a recent arrhythmia. These results confirm previous findings and suggest that matching of pollution periods to arrhythmias is important in detecting such associations. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Dockery, DW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Bldg,Suite 415 W,POB 15677,401 Pk Dr, Boston, MA 02115 USA. EM ddockery@hsph.harvard.edu FU NIEHS NIH HHS [ES 00002, ES 09825, T32 ES 070] NR 41 TC 117 Z9 123 U1 0 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 JUN 15 PY 2005 VL 161 IS 12 BP 1123 EP 1132 DI 10.1093/aje/kwi143 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 934HQ UT WOS:000229700300005 PM 15937021 ER PT J AU Matteson, EL Choi, HK Poe, DS Wise, C Lowe, VJ Mcdonald, TJ Rahman, MU AF Matteson, EL Choi, HK Poe, DS Wise, C Lowe, VJ Mcdonald, TJ Rahman, MU TI Etanercept therapy for immune-mediated cochleovestibular disorders: A multi-center, open-label, pilot study SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE hearing loss; immune-mediated cochleovestibular disease; positron emission tomography; etanercept ID SENSORINEURAL HEARING-LOSS; SPEECH-DISCRIMINATION SCORES; INNER-EAR DISORDERS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE REACTIVITY; CONTROLLED-TRIAL; COGANS SYNDROME; METHOTREXATE; RECEPTOR; DISEASE AB Objective. Immune-mediated cochleovestibular disorders (IMCVDs) continue to present a diagnostic and therapeutic challenge. Antirheumatic agents, commonly employed for IMCVDs, are associated with variable efficacy and sometimes with serious side effects. The objective of the current study was to preliminarily evaluate the efficacy of etanercept therapy for IMCVD. Methods. In this open-label prospective pilot study, 23 patients with bilateral IMCVDs or symptoms of bilateral Meniere's disease were treated with etanercept (25 mg twice weekly, by subcutaneous injection) for 24 weeks. All participants showed progressive hearing loss within 3 months prior to the study and responded to prednisone therapy. Hearing improvement was defined as an improvement of sensorineural hearing from baseline, in at least one ear, of 15 dB or more in the pure-tone air conduction thresholds, or an increase of more than 12% in word identification score. When present, vertigo and tinnitus were assessed by frequency and severity of attack and a functional level scale. Limited serial positron emission tomography (PET) of the inner ear region was performed in 5 patients to assess disease activity. Results. There were 12 female (52%) and 11 male patients with a mean age of 48 years. Hearing improved in 7 (30%) patients, was unchanged in 13 (57%), and worsened in 3 (13%). Of 21 patients with tinnitus, this symptom improved in 7 (33%), was unchanged in 10 (48%), and worsened in 3 (13%). Of 16 patients with vertigo, 8 (50%) were improved, 7 (47%) unchanged, and 1 (3%) worse at the end of the study. Etanercept was generally well tolerated. PET was positive on one ear of 2 of 5 patients, remained positive with treatment on 1 of these, and was initially positive in 1 deaf ear, becoming negative at followup. Conclusion. These prospective pilot data suggest that etanercept therapy is safe among patients with IMCVDs. However, these data do not suggest substantial efficacy of etanercept among patients with IMCVDs in improving hearing loss. There appeared to be stabilization or improvement of hearing in 87% in this group of patients with pretreatment intractable progressive hearing loss. However, the study endpoint of improvement in 70% of patients was not attained. This short-term effect of possible stabilization requires further study. PET scanning was not useful as a tool to evaluate hearing loss in a limited subset of patients. C1 Mayo Clin, Coll Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. RP Matteson, EL (reprint author), Mayo Clin, Coll Med, 200 1st SW, Rochester, MN 55905 USA. EM matteson.eric@mayo.edu NR 29 TC 36 Z9 39 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2005 VL 53 IS 3 BP 337 EP 342 DI 10.1002/art.21179 PG 6 WC Rheumatology SC Rheumatology GA 933RV UT WOS:000229651500005 PM 15934127 ER PT J AU Bhattacharyya, T Levin, R Vrahas, MS Solomon, DH AF Bhattacharyya, T Levin, R Vrahas, MS Solomon, DH TI Nonsteroidal antiinflammatory drugs and nonunion of humeral shaft fractures SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE NSAIDs; fracture healing; opioids; confounding ID DIAPHYSIS AB Objective. To analyze the relationship between nonunion of humeral shaft fractures and nonsteroidal antiinflammatory drug (NSAID) exposure in older adults. Methods. A cohort of 9,995 patients with humeral shaft fractures was identified using diagnosis and procedure codes from a Medicare database of > 500,000 patients. Prescription NSAID as well as prescription opioid use was assessed from pharmacy claims data for 3 30-day periods immediately after the initial fracture. Nonunion was defined by the presence of procedure codes for repair of nonunion 90-365 days after the index fracture. We examined the association between NSAIDs and nonunion using multivariate Cox proportional hazards models. Results. Of the 9,995 humeral shaft fractures, 105 patients developed nonunions (1.1%), and 1,032 (10.3%) were exposed to NSAIDs in the 90 days after fracture. NSAID exposure within the first 90 days was significantly associated with nonunion (relative risk [RR] 3.7, 95% confidence interval [95% CI] 2.4-5.6). When indicators for exposure to NSAIDs during each of the 3 30-day windows were placed into the same multivariate model, only the period 61-90 days postfracture was significantly associated with nonunion (RR 3.9, 95% CI 2.0-6.2). We observed a similar association between opioids and nonunion, with exposure to opioids between 61 and 90 days associated with nonunion (RR 2.7, 95% CI 1.5-5.2), but exposure to opioids during neither of the 2 earlier 30-day periods significantly associated with nonunion. Conclusion. We found that exposure to nonselective NSAIDs or opioids in the period 61-90 days after a humeral shaft fracture was associated with nonunion. Although these associations may be causal, they are more likely to reflect the use of analgesics by patients with painful nonhealing fractures. Conclusion. We found that exposure to nonselective NSAIDs or opioids in the period 61-90 days after a humeral shaft fracture was associated with nonunion. Although these associations may be causal, they are more likely to reflect the use of analgesics by patients with painful nonhealing fractures. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02120 USA. Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org FU NIAMS NIH HHS [AR-48264, AR-48616]; NIDA NIH HHS [DA-15507] NR 11 TC 47 Z9 48 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2005 VL 53 IS 3 BP 364 EP 367 DI 10.1002/art.21170 PG 4 WC Rheumatology SC Rheumatology GA 933RV UT WOS:000229651500009 PM 15934108 ER PT J AU Smoller, JW Yamaki, LH Fagerness, JA Biederman, J Racette, S Laird, NM Kagan, J Snidman, N Faraone, SV Hirshfeld-Becker, D Tsuang, MT Slaugenhaupt, SA Rosenbaum, JF Sklar, PB AF Smoller, JW Yamaki, LH Fagerness, JA Biederman, J Racette, S Laird, NM Kagan, J Snidman, N Faraone, SV Hirshfeld-Becker, D Tsuang, MT Slaugenhaupt, SA Rosenbaum, JF Sklar, PB TI The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE CRH; behavioral inhibition; temperament; anxiety; panic disorder; haplotype; genetic association ID ANXIETY-LIKE BEHAVIOR; TRANSMISSION/DISEQUILIBRIUM TEST; FEARFUL TEMPERAMENT; AMYGDALAR RESPONSE; ASSOCIATION TESTS; RHESUS-MONKEYS; SOCIAL ANXIETY; BRAIN ACTIVITY; ANIMAL-MODELS; CRH GENE AB Background. Behavioral inhibition to The unfamiliar (BI) is a heritable temperamental phenotype involving the tendancy to display fearful, avoidant, or shy behavior in novel situations. BI is a familial and developmental risk factor for panic and phobic anxiety disorders. We previously observed an association between BI and a microsatellite marker linked to the corticotropin releasing hormone (CRH) gene in children at risk for panic disorder. To evaluate this further we genotyped additional families for this marker and a panel of markers encompassing the CRH locus. Methods. Sixty-two families that included parents with panic disorder and children who underwent laboratoy-based behavioral observations were studied. Family-based association tests and haplotype analysis were used to evaluate the association between BI and polymorphisms spanning the CRH locus. Results: We examined a set of markers which we found to reside in a block of strong linkage disequilibrium encompassing the CRH locus. The Biphenotype was associated with the microsatellite marker (p =.0016) and three single nucleotide polymorphisms (SNPs), including a SNP in the coding sequence of the gene (p =.0,43). Haplotype-specific tests revealed association with a haplotype comprising all of the markets (p =.015). Conclusions. These results suggest that the CRH gene influences inhibited temperament, a risk factor for panic and phobic anxiety disorders, Genetic studies of anxiey-related temperament represent an important strategy,for identifying the genetic basis of anxiety disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Inst Psychiat Epidemiol & Genet, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, San Diego, CA 92103 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St WAC 812, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K-08 MH01770-02] NR 69 TC 97 Z9 101 U1 5 U2 15 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 JUN 15 PY 2005 VL 57 IS 12 BP 1485 EP 1492 DI 10.1016/j.biopsych.2005.02.018 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 938MO UT WOS:000230007700003 PM 15953484 ER PT J AU Daley, GQ AF Daley, GQ TI Simplifying hESC culture SO BLOOD LA English DT Editorial Material ID GROWTH; CELLS AB Human embryonic stem cells are a valuable resource for research and cell replacement therapy but are notoriously cumbersome to culture. Bhatia and colleagues show that an increased dose of basic fibroblast growth factor eliminates the need for feeder layer coculture. C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4550 EP 4550 DI 10.1182/blood-2005-03-1265 PG 1 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300010 ER PT J AU Re, D Thomas, RK Behringer, K Diehl, V AF Re, D Thomas, RK Behringer, K Diehl, V TI From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential SO BLOOD LA English DT Review ID REED-STERNBERG CELLS; NF-KAPPA-B; HISTONE DEACETYLASE INHIBITOR; IMMUNOGLOBULIN GENE REARRANGEMENTS; INVOLVED-FIELD RADIOTHERAPY; INDUCED APOPTOSIS; C-FLIP; RANDOMIZED TRIAL; IN-VIVO; DEPSIPEPTIDE FR901228 AB Reclassification of Hodgkin disease as Hodgkin lymphoma (HL) represents a milestone in the lymphoma field, awarding recent insights in the molecular biology of Hodgkin and Reed-Sternberg (HRS) cells and their environment. This review summarizes antiapoptotic and proproliferative pathways involved in the pathogenesis of this disease with the ultimate goal of translating laboratory knowledge into clinical decision making. The focus is on potential targets and novel drugs, which are discussed in the context of the complex biology of HL. Considering that HL patients are more likely to die from acute and late treatment-related toxicities than from HL itself, the introduction of targeted, biologically based therapies for HL patients with palliative and eventually curative intention might be justified. (c) 2005 by The American Society of Hematology. C1 Burnham Inst, John Reed Lab, La Jolla, CA 92037 USA. Univ Cologne, Dept Internal Med 1, D-5000 Cologne, Germany. Univ Cologne, CMMC, D-5000 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Re, D (reprint author), Burnham Inst, John Reed Lab, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM dre@burnham.org NR 100 TC 60 Z9 63 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 JUN 15 PY 2005 VL 105 IS 12 BP 4553 EP 4560 DI 10.1182/blood-2004-12-4750 PG 8 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300012 PM 15728122 ER PT J AU Ebert, BL Lee, MM Pretz, JL Subramanian, A Mak, R Golub, TR Sieff, CA AF Ebert, BL Lee, MM Pretz, JL Subramanian, A Mak, R Golub, TR Sieff, CA TI An RNA interference model of RPS 19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray SO BLOOD LA English DT Article ID RIBOSOMAL-PROTEIN S19; IN-VITRO RESPONSE; ERYTHROID PROGENITORS; TRANSCRIPTIONAL REGULATION; MAMMALIAN-CELLS; C-KIT; EXPRESSION; LIGAND; ERYTHROPOIESIS; PROLIFERATION AB Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia, is a model disease for the study of erythroid differentiation but is poorly understood. RPS19 is the only gene yet to have been associated with DBA, but its relevance to erythroid differentiation is unclear. The molecular basis for the stimulation of erythropoiesis by glucocorticoids in patients with DBA has not been identified. We demonstrate that targeted degradation of the RPS19 transcript, through retroviral expression of short hairpin RNAs (shRNAs), blocks the proliferation and differentiation of erythroid progenitor cells in cultured human CD34(+) cells. Treatment of RPS19-deficient cells with dexamethasone restores erythroid differentiation to normal levels. We investigated the molecular basis of pharmacologic therapies for DBA using oligonucleotide microarrays to survey gene expression in CD34(+) cells treated with combinations of dexamethasone, erythropoietin, stem cell factor, and interleukin-3. Dexamethasone did not alter expression of RPS19 but activated a genetic program that includes a set of key hematopoietic regulatory genes. Genes specific to erythroid progenitor cells were up-regulated by dexamethasone, while genes specific to nonerythroid lineages were down-regulated. Deficiency of RPS19 therefore blocks proliferation of immature erythroid progenitor cells, and dexamethasone activates proliferation of the same cell population through mechanisms independent of RPS19. (c) 2005 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Sieff, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Rm M612,44 Binney St, Boston, MA 02115 USA. EM golub@broad.mit.edu FU NCI NIH HHS [T32 CA009172] NR 40 TC 60 Z9 60 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4620 EP 4626 DI 10.1182/blood-2004-08-3313 PG 7 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300022 PM 15755903 ER PT J AU O'Sullivan, BP Linden, MD Frelinger, AL Barnard, MR Spencer-Manzon, M Morris, JE Salem, RO Laposata, M Michelson, AD AF O'Sullivan, BP Linden, MD Frelinger, AL Barnard, MR Spencer-Manzon, M Morris, JE Salem, RO Laposata, M Michelson, AD TI Platelet activation in cystic fibrosis SO BLOOD LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; SURFACE P-SELECTIN; IN-VIVO; FLOW-CYTOMETRY; ACID; GENE; ATP; IDENTIFICATION; CFTR; ABNORMALITIES AB Cystic fibrosis (CF) is caused by a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). We examined platelet function in CF patients because lung inflammation is part of this disease and platelets contribute to inflammation. CF patients had increased circulating leukocyte-platelet aggregates and increased platelet responsiveness to agonists compared with healthy controls. CF plasma caused activation of normal and CF platelets; however, activation was greater in CF platelets. Furthermore, washed CF platelets also showed increased reactivity to agonists. CF platelet hyperreactivity was incompletely inhibited by prostaglandin E-1 (PGE(1)). As demonstrated by Western blotting and reverse-transcriptase-polymerase chain reaction (RT-PCR), there was neither CFTR nor CFTR-specific mRNA in normal platelets. There were abnormalities in the fatty acid composition of membrane fractions of CF platelets. In summary, CF patients have an increase in circulating activated platelets and platelet reactivity, as determined by monocyte-platelet aggregation, neutrophil-platelet aggregation, and platelet surface P-selectin. This increased platelet activation in CF is the result of both a plasma factor(s) and an intrinsic platelet mechanism via cyclic adenosine monophosphate (cAMP)/adenylate cyclase, but not via platelet CFTR. Our findings may account, at least in part, for the beneficial effects of ibuprofen in CF. (c) 2005 by The American Society of Hematology. C1 UMass Mem Hlth Care, Dept Pediat, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Worcester, MA 01605 USA. Genzyme Corp, Dept Mol Biol, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP O'Sullivan, BP (reprint author), UMass Mem Hlth Care, Dept Pediat, 55 Lake Ave N, Worcester, MA 01655 USA. EM osuilivb@ummhc.org RI Linden, Matthew/G-9644-2012; OI Linden, Matthew/0000-0002-9126-2166 NR 47 TC 59 Z9 59 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 JUN 15 PY 2005 VL 105 IS 12 BP 4635 EP 4641 DI 10.1182/blood-2004-06-2098 PG 7 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300024 PM 15705796 ER PT J AU Alvarez, JV Febbo, PG Ramaswamy, S Loda, M Richardson, A Frank, DA AF Alvarez, JV Febbo, PG Ramaswamy, S Loda, M Richardson, A Frank, DA TI Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; STAT3 ACTIVATION; CELLULAR-TRANSFORMATION; V-SRC; EXPRESSION; SURVIVAL; INHIBITION; APOPTOSIS; PROLIFERATION; ANGIOGENESIS AB Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation. However, the full complement of target genes that STAT3 regulates to promote oncogenesis is not known. We created a system to express a constitutively active form of STAT3, STAT3-C, in mouse fibroblasts and used it to identify STAT3 targets. We showed that a subset of these targets, which include transcription factors regulating cell growth, survival, and differentiation, are coexpressed in a range of human tumors. Using immunohistochemical staining of tissue micro-arrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3. Finally, we showed that STAT3 is required for the expression of these genes in a breast cancer cell line. Taken together, these results identify a cohort of STAT3 targets that may mediate its role in oncogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 522B, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu FU NCI NIH HHS [CA79547] NR 34 TC 111 Z9 116 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 JUN 15 PY 2005 VL 65 IS 12 BP 5054 EP 5062 DI 10.1158/0008-5472.CAN-04-4281 PG 9 WC Oncology SC Oncology GA 934UN UT WOS:000229734300015 PM 15958548 ER PT J AU Wonsey, DR Follettie, MT AF Wonsey, DR Follettie, MT TI Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; S-PHASE; HEPATOCELLULAR CARCINOMAS; HEPATOCYTE ENTRY; FACTOR HFH-11B; FACTOR TRIDENT; DNA-DAMAGE; AURORA-A; EXPRESSION; PROTEIN AB Expression of the forkhead transcription factor FoxM1 correlates with proliferative status in a variety of normal and transformed cell types. Elevated expression of FoxM1 has been noted in both hepatocellular carcinoma and basal cell carcinoma. However, whether FoxM1 expression is essential for the viability of transformed cells is unknown. We report here that the expression of FoxM1 is significantly elevated in primary breast cancer. Microarray analysis shows that FoxM1 regulates genes that are essential for faithful chromosome segregation and mitosis, including Nek2, KIF20A, and CENP-A. Loss of FoxM1 expression generates mitotic spindle defects, delays cells in mitosis, and induces mitotic catastrophe. Time-lapse microscopy indicates that depletion of FoxM1 generates cells that enter mitosis but are unable to complete cell division, resulting in either mitotic catastrophe or endoreduplication. These findings indicate that FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting FoxM1 represents a therapeutic strategy to target breast cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Wyeth Res, Dept Discovery Med, Cambridge, MA USA. RP Wonsey, DR (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 649, Boston, MA 02115 USA. EM Diane_Wonsey@dfci.harvard.edu NR 45 TC 207 Z9 221 U1 3 U2 11 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 JUN 15 PY 2005 VL 65 IS 12 BP 5181 EP 5189 DI 10.1158/0008-5472.CAN-04-4059 PG 9 WC Oncology SC Oncology GA 934UN UT WOS:000229734300029 PM 15958562 ER PT J AU Sharma, S Yang, SC Zhu, L Reckamp, K Gardner, B Baratelli, F Huang, M Batra, RK Dubinett, SM AF Sharma, S Yang, SC Zhu, L Reckamp, K Gardner, B Baratelli, F Huang, M Batra, RK Dubinett, SM TI Tumor cyclooxygenase-2/prostaglandin E-2-dependent promotion of FOXP3 expression and CD4(+)CD25(+) T regulatory cell activities in lung cancer SO CANCER RESEARCH LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; PERIPHERAL-BLOOD; CYCLOOXYGENASE-2-DEPENDENT INVASION; PROSTAGLANDIN E(2); SOLUBLE MEDIATORS; DOWN-REGULATION; CUTTING EDGE; TGF-BETA; LYMPHOCYTES; APOPTOSIS AB Cyclooxygenase (COX)-2 and its product prostaglandin (PG) E-2 underlie an immunosuppressive network that is important in the pathogenesis of non-small cell lung cancer. CD4(+)CD25(+) T regulatory (Treg) cells play an important role in maintenance of immunologic self-tolerance. CD4(+)CD25(+) Treg cell activities increase in lung cancer and appear to play a role in suppressing antitumor immune responses. Definition of the pathways controlling Treg cell activities will enhance our understanding of limitation of the host antitumor immune responses. Tumor-derived COX-2/PGE(2) induced expression of the Treg cell-specific transcription factor, Foxp3, and increased Treg cell activity. Assessment of E-prostanoid (EP) receptor requirements revealed that PGE(2)-mediated induction of Treg cell Foxp3 gene expression was significantly reduced in the absence of the EP4 receptor and ablated in the absence of the EP2 receptor expression. In vivo, COX-2 inhibition reduced Treg cell frequency and activity, attenuated Foxp3 expression in tumor-infiltrating lymphocytes, and decreased tumor burden. Transfer of Treg cells or administration of PGE(2) to mice receiving COX-2 inhibitors reversed these effects. We conclude that inhibition of COX-2/PGE(2) suppresses Treg cell activity and enhances antitumor responses. C1 Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med,Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med,Lung Canc Res Program, 37-131,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [1P50 CA90388, R01 CA85686] NR 52 TC 256 Z9 293 U1 2 U2 7 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 JUN 15 PY 2005 VL 65 IS 12 BP 5211 EP 5220 DI 10.1158/0008-5472.CAN-05-0141 PG 10 WC Oncology SC Oncology GA 934UN UT WOS:000229734300033 PM 15958566 ER PT J AU Gordon, GJ Rockwell, GN Godfrey, PA Jensen, RV Glickman, JN Yeap, BY Richards, WG Sugarbaker, DJ Bueno, R AF Gordon, GJ Rockwell, GN Godfrey, PA Jensen, RV Glickman, JN Yeap, BY Richards, WG Sugarbaker, DJ Bueno, R TI Validation of genomics-based prognostic tests in malignant pleura mesothelioma SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION PROFILING DATA; CELL LUNG-CANCER; SURVIVAL; ADENOCARCINOMA; THROMBOMODULIN; MICROARRAYS; THERAPY; RATIOS; MARKER; CD24 AB Purpose: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme. Experimental Design: Gene expression data using high-density oligonucleotide microarrays (similar to 22,000 genes) were obtained for a new cohort of human MPM tumors from patients undergoing similar treatments (n = 39). The relative expression levels for specific genes were also determined using real-time quantitative reverse transcription-PCR. We also used a subset of these tumors associated with widely divergent patient survival (n = 23) as a training set to identify new treatment-specific candidate prognostic molecular markers and gene ratio-based prognostic tests. The predictive nature of these newly discovered markers and gene ratio-based prognostic tests were then examined in an independent group of tumors (n = 52) using microarray data and quantitative reverse transcription-PCR. Results: Previously described MPM prognostic genes and gene ratio-based prognostic tests predicted clinical outcome in 39 independent MPM tumor specimens in a statistically significant manner. Newly discovered treatment-specific prognostic genes and gene ratio-based prognostic tests were highly accurate and statistically significant when examined in an independent group of 52 tumors from patients undergoing similar treatment. Conclusions: The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Thorac Surg Oncol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Cambridge, MA 02138 USA. RP Gordon, GJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM ggordon@partners.org FU NCI NIH HHS [CA-100315-01, CA-102591-01, CA-105249-02, R03 CA105249, R21 CA100315, R33 CA100315] NR 26 TC 49 Z9 49 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 JUN 15 PY 2005 VL 11 IS 12 BP 4406 EP 4414 DI 10.1158/1078-0432.CCR-04-2181 PG 9 WC Oncology SC Oncology GA 934RM UT WOS:000229725900020 PM 15958625 ER PT J AU Gribben, JG Ryan, DP Boyajian, R Urban, RG Hedley, ML Beach, K Nealon, P Matulonis, U Campos, S Gilligan, TD Richardson, PG Marshall, B Neuberg, D Nadler, LM AF Gribben, JG Ryan, DP Boyajian, R Urban, RG Hedley, ML Beach, K Nealon, P Matulonis, U Campos, S Gilligan, TD Richardson, PG Marshall, B Neuberg, D Nadler, LM TI Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; CANCER VACCINES; IMMUNOTHERAPY; CYTOCHROME-P450; BLOOD AB Purpose: The carcinogen activator cytochrome P450 1B1 (CYP1Bl) is expressed on almost all human tumors with rare expression on normal tissues. Anti-CYP1B1-specific T cells kill CYP1B1-expressing tumors, providing the rationale to examine CYP1B1 as a target for immunotherapy. Experimental Design: ZYC300, a plasmid DNA of CYP1B1 encapsulated in biodegradable poly-DL-lactide-coglycolide microparticles, was used in a phase I clinical trial to treat 17 patients with advanced stage, progressive cancer. ZYC300 was administered i.m. at a fixed dose of 400 mu g every other week for up to 12 doses. Results: Thirteen patients received six vaccinations and five received all 12 doses. No significant adverse events were observed. Six patients developed immunity to CYP1B1, three of whom developed disease stabilization. All but 1 of 11 patients who did not develop immunity to CYP1B1 progressed and did not respond to salvage therapy. Five patients who developed immunity to CYP1B1 required salvage therapy for progressive metastatic disease and showed marked response to their next treatment regimen, most of which lasted longer than 1 year. Conclusions: The association between immunity to CYP1B1 and response to next salvage therapy was not expected. Because six of the seven patients who had clinical benefit regardless of the nature of salvage therapy had developed immunity to CYP1B1, it seems highly unlikely that this occurred by chance alone. Regardless of the mechanism(s) that induced tumor regression, these findings force us to rethink how the generation of antitumor immunity might be integrated into the treatment of cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. MGI Pharma Biol, Lexington, MA USA. RP Nadler, LM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lee_nadler@dfci.harvard.edu OI Gilligan, Timothy/0000-0003-2308-9303 NR 19 TC 92 Z9 99 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 JUN 15 PY 2005 VL 11 IS 12 BP 4430 EP 4436 DI 10.1158/1078-0432.CCR-04-2111 PG 7 WC Oncology SC Oncology GA 934RM UT WOS:000229725900022 PM 15958627 ER PT J AU Wu, CJ Biernacki, M Kutok, JL Rogers, S Chen, LY Yang, XF Soiffer, RJ Ritz, J AF Wu, CJ Biernacki, M Kutok, JL Rogers, S Chen, LY Yang, XF Soiffer, RJ Ritz, J TI Graft-versus-leukemia target antigens in chronic myelogenous leukemia are expressed on myeloid progenitor cells SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOCYTIC-LEUKEMIA; TUMOR GENE WT1; DENDRITIC CELLS; STEM-CELLS; T-LYMPHOCYTES; BONE-MARROW; CLINICAL-APPLICATION; CROSS-PRESENTATION; IMMUNE-RESPONSE; MALIGNANT CLONE AB Purpose: Donor lymphocyte infusion (DLI) reliably induces durable remission in 75% to 80% of patients with relapsed chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation. We previously reported the identification of a high titer - specific immunoglobulin G response against two novel leukemia-associated antigens, CML28 and CML66, which correlated with immune-induced remission. The present studies characterize expression of CML28 and CML66 in primary hematopoietic tissues. Experimental Design: Specific monoclonal antibodies to CML28 and CML66 were developed and used to detect antigen expression in leukemia cell lines and primary leukemia tissue on Western blot and immunohistochemistry. Expression patterns were confirmed by antigen-specific real-time PCR. Results: Both CML28 and CML66 were highly expressed in leukemic blasts from patients with acute myelogenous leukemia and CIVIL blast crisis but barely detectable in normal bone marrow, normal peripheral blood, or leukemic cells from patients with stable-phase CIVIL. In contrast, purified CD34(+) progenitors from normal individuals and patients with stable-phase CIVIL expressed high levels of CML28 and CML66 transcript and protein. Immunohistochemical staining for CML66 confirmed rare staining of myeloid precursors in normal marrow and diffuse staining of myeloblastic cells in acute myelogenous leukemia and blast crisis CIVIL marrows. Conclusions: The expression patterns of CML28 and CML66 are strikingly similar and suggest that antigen expression may play a role in shaping the post-DLI antibody repertoire. The CD34(+) restricted pattern of expression of CML28 and CML66 is particularly relevant in light of the notion that DLI likely exerts its curative effect by targeting antigens present in self-renewing malignant progenitor populations in CIVIL. C1 Dana Farber Canc Inst, Div Hematol Malignacies, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Div Hematol Malignacies, 44 Binney St, Boston, MA 02115 USA. EM CWU@PARTNERS.ORG RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996]; NHLBI NIH HHS [KO8 HL04293]; NIAID NIH HHS [AI29537] NR 45 TC 34 Z9 37 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 JUN 15 PY 2005 VL 11 IS 12 BP 4504 EP 4511 DI 10.1158/1078-0432.CCR-05-0036 PG 8 WC Oncology SC Oncology GA 934RM UT WOS:000229725900031 PM 15958636 ER PT J AU Anstead, GM Corcoran, G Lewis, J Berg, D Graybill, JR AF Anstead, GM Corcoran, G Lewis, J Berg, D Graybill, JR TI Refractory coccidioidomycosis treated with posaconazole SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FLUCONAZOLE; IMMITIS AB Background. Disseminated coccidioidomycosis ( which is caused by the endemic fungi of the genus Coccidioides) can be a life-threatening systemic fungal infection. Although conventional antifungal therapies have activity against Coccidioides, the disease can be refractory to standard therapies. Drug-associated toxicities also may limit the clinical utility of the standard antifungal drugs. In addition, relapses in patients with disseminated coccidioidomycosis are common, making long-term management of this disease challenging. Methods. We report the outcomes of 6 patients with coccidioidomycosis who were treated with posaconazole salvage therapy after treatment with conventional antifungal therapies failed to produce sustained clinical improvement. Patients were administered posaconazole oral suspension 800 mg/ day in divided doses as part of an open-label clinical trial. A modified version of the Mycoses Study Group Coccidioides scoring system was used to evaluate the burden of disease. Posaconazole therapy resulted in rapid clinical improvements in the signs and symptoms of coccidioidomycosis. Results. At the end of therapy, 5 of 6 patients had successful outcomes. Posaconazole was well tolerated despite long-termadministration (1 - 2 years), and 2 patients continued to receive posaconazole maintenance therapy at the time of writing Conclusions. The successful outcomes observed in this case series suggest that posaconazole is an effective therapy for coccidioidomycosis. C1 Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Graybill, JR (reprint author), Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM graybill@uthscsa.edu NR 16 TC 68 Z9 72 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 JUN 15 PY 2005 VL 40 IS 12 BP 1770 EP 1776 DI 10.1086/430303 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 927OW UT WOS:000229204300010 PM 15909265 ER PT J AU Hooper, DC AF Hooper, DC TI Efflux pumps and nosocomial antibiotic resistance: A primer for hospital epidemiologists SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; STREPTOCOCCUS-PNEUMONIAE; FLUOROQUINOLONE RESISTANCE; MULTIDRUG-RESISTANCE; NEISSERIA-GONORRHOEAE; QUINOLONE RESISTANCE; CAMPYLOBACTER-JEJUNI; MEDIATED RESISTANCE C1 Harvard Univ, Div Infect Dis, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Infect Control Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, R01 AI23988] NR 65 TC 28 Z9 30 U1 1 U2 7 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 JUN 15 PY 2005 VL 40 IS 12 BP 1811 EP 1817 DI 10.1086/430381 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 927OW UT WOS:000229204300017 PM 15909271 ER PT J AU Devgan, V Mammucari, C Millar, SE Brisken, C Dotto, GP AF Devgan, V Mammucari, C Millar, SE Brisken, C Dotto, GP TI P21(WAF1/Cip1) is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation SO GENES & DEVELOPMENT LA English DT Article DE differentiation; stem cell potential; transcription; chromatin; E2F-1; c-Myc; p300 ID NF-KAPPA-B; BETA-CATENIN; EPIDERMAL DIFFERENTIATION; SKIN CARCINOGENESIS; KERATINOCYTE GROWTH; SIGNALING PATHWAYS; TUMOR SUPPRESSION; DNA-REPLICATION; MOUSE SKIN; INHIBITORS AB In keratinocytes, the cyclin/CDK inhibitor p21(WAF1)/(Cip1) is a direct transcriptional target of Notch1 activation; loss of either the p21 or Notch1 genes expands stem cell populations and facilitates tumor development. The Notch1 tumor-suppressor function was associated with down-regulation of Wnt signaling. Here, we show that suppression of Wnt signaling by Notch1 activation is mediated, at least in part, by down-modulation of Wnts,gene expression. p21 is a negative regulator of Wnts transcription downstream of Notch1 activation, independently of effects on the cell cycle. More specifically, expression of the Wnt4 gene is under negative control of endogenous p21 both in vitro and in vivo. p21 associates with the E2F-1 transcription factor at the Wnt4 promoter and causes curtailed recruitment of c-Myc and p300, and histone hypoacetylation at this promoter. Thus, p21 acts as a selective negative regulator of transcription and links the Notch and Wnt signaling pathways in keratinocyte growth control. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. Swiss Canc Res Inst, CH-1066 Epalinges, Switzerland. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM gdotto@partners.org FU NCI NIH HHS [CA73796, R01 CA073796, P01 CA016038, CA16038]; NIAMS NIH HHS [R01 AR039190, AR39190] NR 42 TC 153 Z9 155 U1 0 U2 5 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 JUN 15 PY 2005 VL 19 IS 12 BP 1485 EP 1495 DI 10.1101/gad.341405 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 938FB UT WOS:000229984200011 PM 15964998 ER PT J AU Li, Q Montalbetti, N Shen, PY Dai, XQ Cheeseman, CI Karpinski, E Wu, GQ Cantiello, HF Chen, XZ AF Li, Q Montalbetti, N Shen, PY Dai, XQ Cheeseman, CI Karpinski, E Wu, GQ Cantiello, HF Chen, XZ TI Alpha-actinin associates with polycystin-2 and regulates its channel activity SO HUMAN MOLECULAR GENETICS LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; KIDNEY-DISEASE PROTEIN; PKD1 GENE-PRODUCT; CATION CHANNEL; MDCK CELLS; CYTOPLASMIC DOMAIN; PLASMA-MEMBRANE; RENAL EPITHELIA; NMDA RECEPTOR; PRIMARY CILIA AB Polycystin-2 (PC2) is the product of the PKD2 gene, which is mutated in 10-15% patients of autosomal dominant polycystic kidney disease (ADPKD). PC2 is an integral transmembrane protein and acts as a calcium-permeable cation channel. The functional modulation of this channel by other protein partners remains largely unknown. In the present study, using a yeast two-hybrid approach, we discovered that both intracellular N- and C-termini of PC2 associate with alpha-actinins, actin-binding and actin-bundling proteins important in cytoskeleton organization, cell adhesion, proliferation and migration. The PC2-alpha-actinin association was confirmed by in vitro glutathione S-transferase pull-down and dot blot overlay assays. In addition, the in vivo interaction between endogenous PC2 and alpha-actinins was demonstrated by co-immunoprecipitation in human embryonic kidney 293 and Madin-Darby canine kidney (MDCK) cells, rat kidney and heart tissues and human syncytiotrophoblast (hST) apical membrane vesicles. Immunofluorescence experiments showed that PC2 and alpha-actinin were partially co-localized in epithelial MDCK and inner medullary collecting duct cells, NIH 3T3 fibroblasts and hST vesicles. We studied the functional modulation of PC2 by alpha-actinin in a lipid bilayer electrophysiology system using in vitro translated PC2 and found that alpha-actinin substantially stimulated the channel activity of reconstituted PC2. A similar stimulatory effect of alpha-actinin on PC2 was also observed when hST vesicles were reconstituted in lipid bilayer. Thus, physical and functional interactions between PC2 and alpha-actinin may play an important role in abnormal cell adhesion, proliferation and migration observed in ADPKD. C1 Univ Alberta, Dept Physiol, Membrane Prot Res Grp, Edmonton, AB T6G 2H7, Canada. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Chen, XZ (reprint author), Univ Alberta, Dept Physiol, Membrane Prot Res Grp, 7-29 Med Scu Bldg, Edmonton, AB T6G 2H7, Canada. EM xzchen@ualberta.ca OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 64 TC 70 Z9 73 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2005 VL 14 IS 12 BP 1587 EP 1603 DI 10.1093/hmg/ddi167 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 934HL UT WOS:000229699800002 PM 15843396 ER PT J AU Raitt, MH Connor, WE Morris, C Kron, J Halperin, B Chugh, SS McClelland, J Cook, J MacMurdy, K Swenson, R Connor, SL Gerhard, G Kraemer, DF Oscran, D Marchant, C Calhoun, D Shnider, R McAnulty, J AF Raitt, MH Connor, WE Morris, C Kron, J Halperin, B Chugh, SS McClelland, J Cook, J MacMurdy, K Swenson, R Connor, SL Gerhard, G Kraemer, DF Oscran, D Marchant, C Calhoun, D Shnider, R McAnulty, J TI Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; SUDDEN CARDIAC DEATH; MYOCARDIAL-INFARCTION; N-3; PREVENTION; ARRHYTHMIAS; OMEGA-3-FATTY-ACIDS; ERYTHROCYTES; CONSUMPTION; MYOCYTES AB Context Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF Intervention Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P=.19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P=.007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Baystate Med Ctr, Springfield, MA USA. SW Med Ctr, Vancouver, WA USA. Sacred Heart Med Ctr, Eugene, OR USA. Oregon State Univ, Portland, OR USA. St Vincents Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, 3710 SW US Vet Rd,P-3-CARD, Portland, OR 97239 USA. EM merritt.raitt@med.va.gov FU NCRR NIH HHS [5 M01 RR00334]; NHLBI NIH HHS [R01HL61682] NR 27 TC 222 Z9 234 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 15 PY 2005 VL 293 IS 23 BP 2884 EP 2891 DI 10.1001/jama.293.23.2884 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 935MD UT WOS:000229785500023 PM 15956633 ER PT J AU Mehta, SR Cannon, CP Fox, KAA Wallentin, L Boden, WE Spacek, R Widimsky, P McCullough, PA Hunt, D Braunwald, E Yusuf, S AF Mehta, SR Cannon, CP Fox, KAA Wallentin, L Boden, WE Spacek, R Widimsky, P McCullough, PA Hunt, D Braunwald, E Yusuf, S TI Routine vs selective invasive strategies in patients with acute coronary syndromes - A collaborative meta-analysis of randomized trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID ST-SEGMENT ELEVATION; WAVE MYOCARDIAL-INFARCTION; HIGH-RISK PATIENTS; PLATELET GLYCOPROTEIN IIB/IIIA; UNSTABLE ANGINA-PECTORIS; ARTERY-DISEASE; CONSERVATIVE TREATMENT; UNFRACTIONATED HEPARIN; ANTIPLATELET THERAPY; TROPONIN-T AB Context Patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention. Objective To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies. Data Sources Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews. Study Selection Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy. Data Extraction Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials. Data Synthesis A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [Cl], 0.72-0.93; P=.001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% Cl, 0.77-1.09; P=.33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% Cl, 1.14-2.25; P=.007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% Cl, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy. Conclusions A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies. C1 McMaster Univ, Dept Med, Hamilton, ON L6K 1B8, Canada. Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada. Royal Melbourne Hosp, Melbourne, Vic, Australia. William Beaumont Hosp, Royal Oak, MI 48072 USA. Charles Univ, Sch Med 3, Cardioctr, Univ Hosp Kralovske Vinohrady, Prague, Czech Republic. Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. Hartford Hosp, Henry Low Heart Ctr, Hartford, CT 06115 USA. Univ Uppsala Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden. Royal Infirm, Dept Med, Edinburgh, Midlothian, Scotland. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Mehta, SR (reprint author), McMaster Univ, Dept Med, 237 Barton St E,Room 508, Hamilton, ON L6K 1B8, Canada. EM smehta@mcmaster.ca RI Widimsky, Petr/P-8088-2016 OI Widimsky, Petr/0000-0001-5686-7752 NR 39 TC 425 Z9 457 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 15 PY 2005 VL 293 IS 23 BP 2908 EP 2917 DI 10.1001/jama.293.23.2908 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 935MD UT WOS:000229785500026 PM 15956636 ER PT J AU Feeney, ME Tang, YH Pfafferott, K Roosevelt, KA Draenert, R Trocha, A Yu, XG Verrill, C Allen, T Moore, C Mallal, S Burchett, S McIntosh, K Pelton, SI St John, AA Hazra, R Klenerman, P Altfeld, M Walker, BD Goulder, PJR AF Feeney, ME Tang, YH Pfafferott, K Roosevelt, KA Draenert, R Trocha, A Yu, XG Verrill, C Allen, T Moore, C Mallal, S Burchett, S McIntosh, K Pelton, SI St John, AA Hazra, R Klenerman, P Altfeld, M Walker, BD Goulder, PJR TI HIV-R viral escape in infancy followed by emergence of a variant-specific CTL response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; LONG-TERM NONPROGRESSORS; ORIGINAL ANTIGENIC SIN; INFECTED CHILDREN; IMMUNE-RESPONSES; TYPE-1 INFECTION; IN-VIVO; REPLICATION; SELECTION AB Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Boston Med Ctr, Boston, MA 02118 USA. Queen Elizabeth Hosp, Bridgetown, Barbados. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Feeney, ME (reprint author), 149 13th St,5th Floor, Charlestown, MA 02129 USA. EM mnfeeney@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [K23-AI52078] NR 26 TC 83 Z9 88 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7524 EP 7530 PG 7 WC Immunology SC Immunology GA 935OK UT WOS:000229791400009 PM 15944251 ER PT J AU Choudhury, A Maldonado, MA Cohen, PL Eisenberg, RA AF Choudhury, A Maldonado, MA Cohen, PL Eisenberg, RA TI The role,of host CD4 T cells in the pathogenesis of the chronic graft-versus-host model of systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEAT-STABLE ANTIGEN(HI); ZONE B-CELLS; COSTIMULATORY MOLECULES; CD4-DEFICIENT MICE; UP-REGULATION; AUTOANTIBODY PRODUCTION; INFECTED INDIVIDUALS; AUTOIMMUNE-DISEASE; IL-4 PROMOTES AB Systemic lupus erythematosus is characterized by production of autoantibodies and glomerulonephritis. The murine chronic graft-vs-host (cGVH) model of systemic lupus erythematosus is induced by allorecognition of foreign MHC class II determinants. Previous studies have shown that cGVH could not be induced in CD4 knockout (CD4KO) mice. We have further explored the role of host CD4 T cells in this model. Our studies now show that B cells in CD4KO mice have intrinsic defects that prevent them from responding to allohelp. In addition, B cells in CD4KO mice showed phenotypic differences compared with congeneic C57BL/6 B cells, indicating some degree of in vivo activation and increased numbers of cells bearing a marginal zone B cell phenotype. The transfer of syngeneic CD4 T cells at the time of initiation of cGVH did not correct these B cell abnormalities; however, if CD4 T cells were transferred during the development and maturation of B cells, then the B cells from CD4KO mice acquire the ability to respond in cGVH. These studies clearly indicate that B cells need to coexist with CD4 T cells early in their development to develop full susceptibility to alloactivation signals. C1 Univ Penn, Div Rheumatol, Dept Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Eisenberg, RA (reprint author), Univ Penn, Div Rheumatol, Dept Med, 756 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM raemd@mail.med.upenn.edu FU NIAID NIH HHS [U19-AI-46358]; NIAMS NIH HHS [R01-AR26574, R01-AR34156] NR 50 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7600 EP 7609 PG 10 WC Immunology SC Immunology GA 935OK UT WOS:000229791400018 PM 15944260 ER PT J AU Rigby, WFC Roy, K Collins, J Rigby, S Connolly, JE Bloch, DB Brooks, SA AF Rigby, WFC Roy, K Collins, J Rigby, S Connolly, JE Bloch, DB Brooks, SA TI Structure/function analysis of tristetraprolin (TTP): p38 stress-activated protein kinase and lipopolysaccharide stimulation do not alter TTP function' SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CONTAINING MESSENGER-RNAS; AU-RICH ELEMENTS; TNF-ALPHA; EXPRESSION; PATHWAY; BINDING; STABILIZATION; DEADENYLATION; BIOSYNTHESIS AB Tristetraprolin (TTP) is the only trans-acting factor shown to be capable of regulating AU-rich element-dependent mRNA turnover at the level of the intact animal; however, the mechanism by which TTP mediated RNA instability is unknown. Using an established model system, we performed structure/function analysis with TTP as well as examined the current hypothesis that TTP function is regulated by p38-MAPKAP kinase 2 (MK2) activation. Deletion of either the N- or C-terminal domains inhibited TTP function. Extensive mutagenesis, up to 16%, of serines and threonines, some of which were predicted to mediate proteasomal targeting, did not alter human TTP function. Mutation of the conserved MK2 phosphorylation sites enhanced human TTP function in both resting and p38-stress-activated protein kinase-MK2-activated cells. However, p38-stress-activated protein kinase-MK2 activation did not alter the activity of either wild-type or mutant TTP. TTP localized to the stress granules, with arsenite treatment reducing this localization. In contrast, arsenite treatment enhanced stress granule localization of the MK2 mutant, consistent with the involvement of additional pathways regulating this event. Finally, we determined that, in response to LPS stimulation, human TTP moves onto the polysomes, and this movement occurs in the absence of 14-3-3. Taken together, these data indicate that, although p38 activation alters TTP entry into the stress granule, it does not alter TTP function. Moreover, the interaction of TTP with 14-3-3, which may limit entry into the stress granule, is not involved in the downstream message stabilization events. C1 Vet Affairs Med Ctr, White River Jct, VT 05009 USA. Dartmouth Coll, Dept Med, Lebanon, NH 03756 USA. Dartmouth Coll, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. Baylor Inst Immunol Res, Dallas, TX 75204 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Vet Affairs Med Ctr, Res 151,215 N Main St, White River Jct, VT 05009 USA. EM seth.brooks@dartmouth.edu RI Connolly, John/B-8099-2014 FU NIAID NIH HHS [AI34928]; NIAMS NIH HHS [AR049834] NR 38 TC 42 Z9 45 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7883 EP 7893 PG 11 WC Immunology SC Immunology GA 935OK UT WOS:000229791400052 PM 15944294 ER PT J AU Law, JR Flanery, MA Wirth, S Yanike, M Smith, AC Frank, LM Suzuki, WA Brown, EN Stark, CEL AF Law, JR Flanery, MA Wirth, S Yanike, M Smith, AC Frank, LM Suzuki, WA Brown, EN Stark, CEL TI Functional magnetic resonance imaging activity during the gradual acquisition and expression of paired-associate memory SO JOURNAL OF NEUROSCIENCE LA English DT Article DE medial temporal lobe; hippocampus; recollection; associative; explicit; declarative ID MEDIAL TEMPORAL-LOBE; BASE-LINE CONDITIONS; RECOGNITION MEMORY; BLOOD-FLOW; FMRI; SENSITIVITY; HIPPOCAMPUS; SYSTEM; PET AB Recent neurophysiological findings from the monkey hippocampus showed dramatic changes in the firing rate of individual hippocampal cells as a function of learning new associations. To extend these findings to humans, we used blood oxygenation level-dependent ( BOLD) functional magnetic resonance imaging ( fMRI) to examine the patterns of brain activity during learning of an analogous associative task. We observed bilateral, monotonic increases in activity during learning not only in the hippocampus but also in the parahippocampal and right perirhinal cortices. In addition, activity related to simple novelty signals was observed throughout the medial temporal lobe (MTL) memory system and in several frontal regions. A contrasting pattern was observed in a frontoparietal network in which a high level of activity was sustained until the association was well learned, at which point the activity decreased to baseline. Thus, we found that associative learning in humans is accompanied by striking increases in BOLD fMRI activity throughout the MTL as well as in the cingulate cortex and frontal lobe, consistent with neurophysiological findings in the monkey hippocampus. The finding that both the hippocampus and surrounding MTL cortex exhibited similar associative learning and novelty signals argues strongly against the view that there is a clear division of labor in the MTL in which the hippocampus is essential for forming associations and the cortex is involved in novelty detection. A second experiment addressed a striking aspect of the data from the first experiment by demonstrating a substantial effect of baseline task difficulty on MTL activity capable of rendering mnemonic activity as either "positive" or "negative." C1 Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. Univ Calif Davis, Dept Anesthesiol & Pain Med, Davis, CA 95616 USA. Univ Calif San Francisco, WM Keck Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Stark, CEL (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, Ames Hall 204,3400 N Charles St, Baltimore, MD 21218 USA. EM cstark@jhu.edu OI Frank, Loren/0000-0002-1752-5677 FU NIDA NIH HHS [DA015644, R01 DA015644]; NIMH NIH HHS [MH59733, K02 MH061637, MH61637, R01 MH059733] NR 32 TC 90 Z9 91 U1 2 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 2005 VL 25 IS 24 BP 5720 EP 5729 DI 10.1523/JNEUROSCI.4935-04.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 935XC UT WOS:000229815700007 PM 15958738 ER PT J AU Tsokas, P Grace, EA Chan, P Ma, T Sealfon, SC Iyengar, R Landau, EM Blitzer, RD AF Tsokas, P Grace, EA Chan, P Ma, T Sealfon, SC Iyengar, R Landau, EM Blitzer, RD TI Local protein synthesis mediates a rapid increase in dendritic elongation factor 1A after induction of late long-term potentiation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; LTP; local protein synthesis; mTOR; eEF1A; TOP mRNA ID MESSENGER-RNA TRANSLATION; FREELY MOVING RATS; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; LATE-PHASE; SIGNALING PATHWAY; FACTOR 1-ALPHA; DENTATE GYRUS; F-ACTIN; ACTIVATION AB The maintenance of long-term potentiation (LTP) requires a brief period of accelerated protein synthesis soon after synaptic stimulation, suggesting that an early phase of enhanced translation contributes to stable LTP. The mechanism regulating protein synthesis and the location and identities of mRNAs translated are not well understood. Here, we show in acute brain slices that the induction of protein synthesis-dependent hippocampal LTP increases the expression of elongation factor 1A (eEF1A), the mRNA of which contains a 5' terminal oligopyrimidine tract. This effect is blocked by rapamycin, indicating that the increase in EF1A expression is mediated by the mammalian target of rapamycin ( mTOR) pathway. We find that mRNA for eEF1A is present in pyramidal cell dendrites and that the LTP-associated increase in eEF1A expression was intact in dendrites that had been severed from their cell bodies before stimulation. eEF1A levels increased within 5 min after stimulation in a translation-dependent manner, and this effect remained stable for 3 h. These results suggest a mechanism whereby synaptic stimulation, by signaling through the mTOR pathway, produces an increase in dendritic translational capacity that contributes to LTP maintenance. C1 Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. RP Blitzer, RD (reprint author), Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, Box 1215,1 Gustave L Levy Pl, New York, NY 10029 USA. EM robert.blitzer@mssm.edu FU NIDA NIH HHS [DA15863, DA017135]; NIDDK NIH HHS [DK46943]; NIGMS NIH HHS [GM54508] NR 50 TC 149 Z9 153 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 JUN 15 PY 2005 VL 25 IS 24 BP 5833 EP 5843 DI 10.1523/JNEUROSCI.0599-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 935XC UT WOS:000229815700018 PM 15958750 ER PT J AU Khan, M Haq, E Giri, S Singh, I Singh, AK AF Khan, M Haq, E Giri, S Singh, I Singh, AK TI Peroxisomal participation in psychosine-mediated toxicity: Implications for Krabbe's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE peroxisomes; Krabbe's disease; plasmalogen; redox; oligodendrocytes; psychosine ID GLOBOID-CELL LEUKODYSTROPHY; CHAIN FATTY-ACIDS; RAT-LIVER PEROXISOMES; CYTOCHROME-C-OXIDASE; GLIAL-CELLS; TWITCHER MOUSE; MITOCHONDRIAL-FUNCTION; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; MURINE MODEL AB Psychosine (galactosylsphingosine) accumulation in globoid cell leukodystrophy (Krabbe's disease) results in the loss of myelin and oligodendrocytes. To understand the role of psychosine toxicity in Krabbe's disease, we examined the effects of psychosine on peroxisomal functions and their relationship with reactive oxygen species. Rat C-6 glial cells were treated with psychosine with and without cytokines. Peroxisomal beta-oxidation was significantly inhibited and very long chain fatty acid levels and free radicals were increased in treated cells. Furthermore, psychosine treatment decreased glutathione and ATP levels, plasmalogen content, and expression of alkyl-DHAP synthase. Brain tissue of twitcher mice (animal model of Krabbe's) had decreased beta-oxidation activity, low glutathione, and reduced plasmalogens. Psychosine treatment of rat primary oligodendrocytes inhibited peroxisomal activities. Psychosine-mediated loss of peroxisomal function and free radical production was inhibited with the antioxidant N-acetylcysteine in glial cells. Our results suggest that inhibition of peroxisomal functions and increased free radical production by psychosine may be partly responsible for oligodendrocyte and myelin loss observed in the Krabbe's brain, and that antioxidant therapy may be useful in the treatment of Krabbe's disease. (c) 2005 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson Vet Aff Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 316 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM singha@musc.edu OI Haq, Ehtishamul/0000-0002-4195-0606 FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 58 TC 47 Z9 49 U1 0 U2 1 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 JUN 15 PY 2005 VL 80 IS 6 BP 845 EP 854 DI 10.1002/jnr.20529 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 931KT UT WOS:000229484900012 PM 15898099 ER PT J AU Kaafarani, HMA Itani, KMF Petersen, LA Thornby, J Berger, DH AF Kaafarani, HMA Itani, KMF Petersen, LA Thornby, J Berger, DH TI Does resident hours reduction have an impact on surgical outcomes? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE resident; work hours; quality of care; NSQIP; surgical outcomes; ACGME ID OF-VETERANS-AFFAIRS; SLEEP-DEPRIVATION; QUALITY; CARE; PERFORMANCE; RISK; IMPROVEMENT; FATIGUE; PROGRAM; WORK AB Background. We assessed the impact of restricting surgical resident work hours as required by the Accreditation Council for Graduate Medical Education (ACGME), on postoperative outcomes. Materials and methods. The divisions of General and Vascular Surgery at the Michael E. DeBakey Houston Veteran Affairs Medical Center implemented a limited work hours schedule effective October 1, 2002. We compared the rate of postoperative morbidity and mortality before and after the new schedule. Clinical data were collected by the VA National Surgical Quality Improvement Program (NSQIP) for the periods of October 1, 2001 to September 30, 2002 (preintervention), and October 1, 2002 to September 30, 2003 (postintervention). We assessed risk-adjusted observed to expected (O/E) ratios of mortality and pre-specified postoperative morbidity for each study period. Results. In the preintervention period, there were 405 general surgery and 202 vascular surgery cases as compared to 382 and 208 cases, respectively in the postintervention period. There were no significant differences in mortality O/E ratios between the pre- and postintervention periods (0.63 versus 0.60 in general surgery; 0.78 versus 0.81 in vascular surgery; P = 0.90 and 0.94, respectively) or in morbidity O/E ratios (1.06versus 1.27 in general surgery; 1.47 versus 1.50 in vascular surgery; P = 0.20 and 0.90, respectively). Conclusion. The restricted resident work hour schedule in general and vascular surgery in our facility did not significantly affect postoperative outcomes. © 2005 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. RP Itani, KMF (reprint author), VABHCS 112, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@med.va.gov NR 20 TC 49 Z9 49 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2005 VL 126 IS 2 BP 167 EP 171 DI 10.1016/j.jss.2004.12.024 PG 5 WC Surgery SC Surgery GA 933BF UT WOS:000229598200006 PM 15919415 ER PT J AU Chan, AT Ma, J Tranah, GJ Giovannucci, EL Rifai, N Hunter, DJ Fuchs, CS AF Chan, AT Ma, J Tranah, GJ Giovannucci, EL Rifai, N Hunter, DJ Fuchs, CS TI Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc ID HEREDITARY HEMOCHROMATOSIS; COLON-CANCER; TRANSFERRIN RECEPTOR; HFE GENE; UNITED-STATES; CLINICAL EXPRESSION; ALCOHOL-CONSUMPTION; NUTRITIONAL FACTORS; CIGARETTE-SMOKING; BREAST-CANCER AB Background. Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study. Methods: Among 32826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided. Results: Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% Cl = 0.63 to 1.47; P-trend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; P-trend = .99), or dietary iron intake (multivariable RR = 1.04, 95% Cl = 0.68 to 1.57; P-trend = .94). Conclusions: Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Canc Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA 55075, CA 09001-27, CA 87969, CA10741]; NHLBI NIH HHS [HL 34594] NR 69 TC 36 Z9 36 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 2005 VL 97 IS 12 BP 917 EP 926 DI 10.1093/jnci/dji165 PG 10 WC Oncology SC Oncology GA 937FA UT WOS:000229908800013 PM 15956653 ER PT J AU Frenkel, D Huang, ZH Maron, R Koldzic, DN Moskowitz, MA Weiner, HL AF Frenkel, D Huang, ZH Maron, R Koldzic, DN Moskowitz, MA Weiner, HL TI Neuroprotection by IL-10-producing MOG CD4+T cells following ischemic stroke SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium of the European-Charcot-Foundation on Preserve the Neuron CY DEC 11-13, 2003 CL Lisbon, PORTUGAL SP European Charcot Fdn DE tolerance; mucosa; IL-10; stroke; T cells; myelin oligodendrocyte glycoprotein ID MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CEREBRAL-ARTERY OCCLUSION; NITRIC-OXIDE SYNTHASE; ORAL TOLERANCE; BRAIN-INJURY; AUTOIMMUNE ENCEPHALOMYELITIS; PHYSIOLOGICAL-RESPONSE; REGULATORY CELLS AB Mucosal tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. In this work we demonstrate the reduction of infarct size following mucosal tolerance by myelin oligodendrocyte glycoprotein (MOG) (35-55) peptide in mouse stroke model. Nasal MOG was most efficacious and reduced ischemic infarct size by 70% at 24 h as well as improving behavior score. Using immunohistological methods and IL-10 -/- mice, we demonstrate the importance of IL-10-producing CD4+ T cells in the reduction of the ischemic infarct volume following middle cerebral artery occlusion (MCAO). Furthermore, adoptive transfer of CD4+ T cells from nasally tolerized mice to untreated mice prior to MCAO surgery significantly decreased stroke size (p < 0.001 vs. control), whereas CD4+ T cells from nasally tolerized IL-10-deficient mice had no significant effect. Based on these results, modulation of cerebral inflammation by mucosal tolerance to myelin antigens may have applicability both as prophylactic therapy and treatment following ischemia attacks. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Weiner, HL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. EM hweiner@rics.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 38 TC 91 Z9 95 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2005 VL 233 IS 1-2 BP 125 EP 132 DI 10.1016/j.jns.2005.03.022 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 939GM UT WOS:000230060500021 PM 15894335 ER PT J AU Stanojevic, V Yao, KM Thomas, MK AF Stanojevic, V Yao, KM Thomas, MK TI The coactivator Bridge-1 increases transcriptional activation by pancreas duodenum homeobox-1 (PDX-1) SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PDX-1; Bridge-1; coactivator; insulin; transcription ID PROMOTER FACTOR-I; INSULIN GENE-TRANSCRIPTION; TYPE-2 DIABETES-MELLITUS; LOOP-HELIX PROTEINS; BETA-CELLS; COOPERATIVE INTERACTIONS; DOMAIN PROTEIN; ISLET CELLS; GLUCOSE; HOMEODOMAIN AB Well-orchestrated transcriptional regulation of pancreatic beta cells is essential for insulin production and glucose homeostasis. Pancreas duodenum homeobox-1 (PDX-1) is a key regulator of glucose-dependent insulin production and glucose metabolism. We find that PDX-1 interacts with the PDZ-domain coactivator Bridge-1 in yeast interaction trap assays. RatBridge-1 and PDX-1 interact directly in GST pull-down assays via Bridge-1 interactions with the amino-terminal transactivation domain of PDX-1. Bridge-1 also interacts with wild-type and mutant human PDX-1 (IPF-1) proteins and strongly interacts with the amino-terminal PDX-1 P63fsdelC (MODY4) mutant protein. Transcriptional activation by PDX-1 is increased by addition of Bridge-1 in multiple contexts, including synergistic activation of a Ga14 reporter by Ga14-Bridge-1 and Ga14-PDX-1 fusion proteins, activation of the somatostatin promoter TAAT1 enhancer, and synergistic activation of the rat insulin I promoter FarFlat enhancer by PDX-1, E12, and E47. We propose that the coactivator Bridge-1 modulates PDX-1 functions in the regulation of its target genes. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Wellman 340,50 Blossom St, Boston, MA 02114 USA. EM mthomas1@partners.org RI Yao, Kwok Ming/C-4457-2009 NR 47 TC 22 Z9 22 U1 0 U2 2 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 JUN 15 PY 2005 VL 237 IS 1-2 BP 67 EP 74 DI 10.1016/j.mce.2005.03.003 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 938YX UT WOS:000230040400007 PM 15885879 ER PT J AU Ongur, D Goff, DC AF Ongur, D Goff, DC TI Obsessive-compulsive symptoms in schizophrenia: associated clinical features, cognitive function and medication status SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; obsessive-compulsive; antipsychotics; cognitive deficits; positive symptoms ID QUETIAPINE AUGMENTATION; OPEN-LABEL; DISORDER; OLANZAPINE; RISPERIDONE; PLACEBO; PERSONALITY; IMPROVEMENT; SERTRALINE; CLOZAPINE AB Objective: To determine the prevalence and clinical significance of obsessive-compulsive (OC) symptoms among a group of stable outpatients with schizophrenia. Methods: We studied 118 patients with schizophrenia from an urban clinic, characterized using clinical symptoms scales, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and neuropsychological testing. We categorized patients into three groups according to severity of OC symptoms and used multivariate linear regression and chi-square tests to compare groups on variables of interest. Results: Only 10 patients (8.8%) had Y-BOCS scores greater than 16, a standard criterion for OCD studies. The patient group with the most OC symptoms (Y-BOCS scores > 11) scored higher on the Hamilton Depression Scale, the positive symptoms subscale of the Positive and Negative Syndromes Scale (PANSS) and its delusions item, but not on any of the neuropsychological tests compared to the other two groups. Patients with most severe compulsive symptoms (but not OC symptoms together, or obsessions alone) were more likely to be treated with olanzapine or clozapine, atypical antipsychotic medications previously reported to induce or worsen OC symptoms. Conclusions: Our results confirm previous findings that patients with schizophrenia and comorbid OC symptoms have more positive symptoms but not the suggestion that such patients are more cognitively impaired than their counterparts without OC symptoms. We suggest possible explanations for discrepancies in the literature, including differences in patient sampling and definition of comorbid OC symptoms. Finally, our data suggest that olanzapine and clozapine may produce or worsen compulsions in some patients; prospective studies need to address this possibility. (c) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Schizophrenia Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ongur, D (reprint author), Massachusetts Gen Hosp, Schizophrenia Res Program, Wang ACC 812,55 Fruit St, Boston, MA 02114 USA. EM dongur@partners.org FU NIMH NIH HHS [MH02025] NR 45 TC 70 Z9 72 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN 15 PY 2005 VL 75 IS 2-3 BP 349 EP 362 DI 10.1016/j.schres.2004.08.012 PG 14 WC Psychiatry SC Psychiatry GA 933XB UT WOS:000229665100021 PM 15885526 ER PT J AU Sbrana, A Dell'Osso, L Benvenuti, A Rucci, P Cassano, P Banti, S Gonnelli, C Doria, MR Ravani, L Spagnolli, S Rossi, L Raimondi, F Catena, M Endicott, J Frank, E Kupfer, DJ Cassano, GB AF Sbrana, A Dell'Osso, L Benvenuti, A Rucci, P Cassano, P Banti, S Gonnelli, C Doria, MR Ravani, L Spagnolli, S Rossi, L Raimondi, F Catena, M Endicott, J Frank, E Kupfer, DJ Cassano, GB TI The psychotic spectrum: validity and reliability of the Structured Clinical Interview for the Psychotic Spectrum SO SCHIZOPHRENIA RESEARCH LA English DT Article DE psychotic; spectrum; questionnaire; schizophrenia; borderline; mood ID BORDERLINE PERSONALITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; DIAGNOSTIC INTERVIEW; SYMPTOMS; POPULATION; DEPRESSION; IDEATION AB This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56127 Pisa, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. Columbia Univ, New York, NY USA. RP Sbrana, A (reprint author), Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Via Roma 67, I-56127 Pisa, Italy. EM alfredosbrana@virgilio.it RI Cassano, Paolo/I-6959-2012 NR 31 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN 15 PY 2005 VL 75 IS 2-3 BP 375 EP 387 DI 10.1016/j.schres.2004.09.016 PG 13 WC Psychiatry SC Psychiatry GA 933XB UT WOS:000229665100023 PM 15885528 ER PT J AU MacCollin, M Chiocca, EA Evans, DG Friedman, JM Horvitz, R Jaramillo, D Lev, M Mautner, VF Niimura, M Plotkin, SR Sang, CN Stemmer-Rachamimov, A Roach, ES AF MacCollin, M Chiocca, EA Evans, DG Friedman, JM Horvitz, R Jaramillo, D Lev, M Mautner, VF Niimura, M Plotkin, SR Sang, CN Stemmer-Rachamimov, A Roach, ES TI Diagnostic criteria for schwannomatosis SO NEUROLOGY LA English DT Article; Proceedings Paper CT International Consensus Conference on Schwannomatosis CY OCT 27, 2003 CL Boston, MA SP Natl Neurofibromatosis Fdn ID MULTIPLE SCHWANNOMAS; TYPE-2 NEUROFIBROMATOSIS; SOMATIC MOSAICISM; GENE; NEURILEMOMAS; TRANSMISSION; MENINGIOMAS; PREVALENCE; MANAGEMENT; MUTATIONS AB The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5 % of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ohio State Univ, Ctr Med, Dept Neurosurg, Columbus, OH 43210 USA. St Marys Hosp, Dept Genet, Manchester M13 0JH, Lancs, England. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. Natl Neurofibromatosis Fdn, New York, NY USA. Univ Hamburg Hosp, Dept Neurol, D-2000 Hamburg, Germany. Rinshoiyaku Inc, Tokyo, Japan. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Wake Forest Univ, Div Child Neurol, Winston Salem, NC 27109 USA. RP MacCollin, M (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA. EM maccollin@helix.mgh.harvard.edu NR 35 TC 157 Z9 164 U1 0 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 JUN 14 PY 2005 VL 64 IS 11 BP 1838 EP 1845 DI 10.1212/01.WNL.0000163982.78900.AD PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000006 PM 15955931 ER PT J AU Rowan, AJ Ramsay, RE Collins, JF Pryor, F Boardman, KD Uthman, BM Spitz, M Frederick, T Towne, A Carter, GS Marks, W Felicetta, J Tomyanovich, ML AF Rowan, AJ Ramsay, RE Collins, JF Pryor, F Boardman, KD Uthman, BM Spitz, M Frederick, T Towne, A Carter, GS Marks, W Felicetta, J Tomyanovich, ML CA VA Cooperat Study 428 Grp TI New onset geriatric epilepsy - A randomized study of gabapentin, lamotrigine, and carbamazepine SO NEUROLOGY LA English DT Article ID TONIC CLONIC SEIZURES; EFFICACY; AGE AB Objective: To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy. Methods: This was an 18-center, randomized, double-blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed seizures. Patients were randomly assigned to one of three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/ day. The primary outcome measure was retention in trial for 12 months. Results: Mean age was 72 years. The most common etiology was cerebral infarction. Patients had multiple medical conditions and took an average of seven comedications. Mean plasma levels at 6 weeks were as follows: GBP 8.67 +/- 4.83 mu g/mL, LTG 2.87 +/- 1.60 mu g/mL, CBZ 6.79 +/- 2.92 mu g/mL. They remained stable throughout the trial. Early terminations: LTG 44.2 %, GBP 51 %, CBZ 64.5 % (p = 0.0002). Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008. Terminations for adverse events: LTG 12.1 %, GBP 21.6 %, CBZ 31 % (p = 0.001). Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p < 0.015. There were no significant differences in seizure free rate at 12 months. Conclusions: The main limiting factor in patient retention was adverse drug reactions. Patients taking lamotrigine ( LTG) or gabapentin ( GBP) did better than those taking carbamazepine. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures. C1 Bronx Vet Adm Med Ctr, Neurol Serv 127, Bronx, NY 10468 USA. VA Med Ctr, Miami, FL USA. VA Med Ctr, Perry Point, MD USA. VA Cooperat Studies Program, Albuquerque, NM USA. VA Med Ctr, Gainesville, FL USA. VA Med Ctr, Denver, CO USA. VA Med Ctr, New Orleans, LA USA. VA Med Ctr, Richmond, VA USA. VA Med Ctr, Dallas, TX USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Phoenix, AZ USA. VA Med Ctr, Chicago, IL USA. RP Rowan, AJ (reprint author), Bronx Vet Adm Med Ctr, Neurol Serv 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM james.rowan@mssm.edu RI Ramsay, R. Eugene/D-4491-2011 NR 20 TC 239 Z9 246 U1 5 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 14 PY 2005 VL 64 IS 11 BP 1868 EP 1873 DI 10.1212/01.WNL.0000167384.68207.3E PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000010 PM 15955935 ER PT J AU Jovin, TG Boosupalli, V Zivkovic, SA Wechsler, LR Gebel, JM AF Jovin, TG Boosupalli, V Zivkovic, SA Wechsler, LR Gebel, JM TI High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer SO NEUROLOGY LA English DT Article ID CEREBROVASCULAR COMPLICATIONS; MUCIN; MALIGNANCY; INFARCTS; EMBOLI AB In addition to etiologies common in the general population, strokes in cancer patients may be caused by hypercoagulable states, hyperviscosity, cardiogenic embolism, and neoplastic vessel infiltration. Intravascular mucins were reported in patients with recurrent thromboembolism. The authors report four patients with metastatic cancer, brain infarcts, and other thromboembolic disease with markedly elevated levels of the tumor marker CA-125 and explore possible associations between this mucinous protein and strokes. C1 Univ Pittsburgh, Med Ctr, Stroke Inst, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Neurol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Childrens Hosp Pittsburgh, Dept Neurol, Pittsburgh, PA USA. RP Jovin, TG (reprint author), Univ Pittsburgh, Med Ctr, Stroke Inst, VA Pittsburgh Healthcare Syst, 200 Lothrop St,Suite C400, Pittsburgh, PA 15213 USA. EM jovintg@upmc.edu NR 10 TC 14 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 14 PY 2005 VL 64 IS 11 BP 1944 EP 1945 DI 10.1212/01.WNL.0000163850.07976.63 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000024 PM 15955949 ER PT J AU Hideshima, T Bradner, JE Wong, J Chauhan, D Richardson, P Schreiber, SL Anderson, KC AF Hideshima, T Bradner, JE Wong, J Chauhan, D Richardson, P Schreiber, SL Anderson, KC TI Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone deacetylase ID THERAPEUTIC APPLICATIONS; CELLS; PS-341; MECHANISMS; RESISTANCE; APOPTOSIS; SEQUELAE; GROWTH; AGENTS AB We have shown that the proteasome inhibitor bortezomib (formerly known as PS-341) triggers significant antitumor activity in multiple myeloma (MM) in both preclinical models and patients with relapsed refractory disease. Recent studies have shown that unfolded and misfolded ubiquitinated proteins are degraded not only by proteasomes, but also by aggresomes, dependent on histone deacetylase 6 (HDAC6) activity. We therefore hypothesized that inhibition of both mechanisms of protein catabolism could induce accumulation of ubiquitinated proteins followed by significant cell stress and cytotoxicity in MM cells. To prove this hypothesis, we used bortezomib and tubacin to inhibit the proteasome and HDAC6, respectively. Tubacin specifically triggers acetylation of alpha-tubulin as a result of HDAC6 inhibition in a dose- and time-dependent fashion. It induces cytotoxicity in MM cells at 72 h with an IC50 of 5-20 mu M, which is mediated by caspase-dependent apoptosis; no toxicity is observed in normal peripheral blood mononuclear cells. Tubacin inhibits the interaction of HDAC6 with dynein and induces marked accumulation of ubiquitinated proteins. It synergistically augments bortezomib-induced cytotoxicity by c-Jun NH2-terminal kinase/caspase activation. Importantly, this combination also induces significant cytotoxicity in plasma cells isolated from MM patient bone marrow. Finally, adherence of MM cells to bone marrow stromal cells confers growth and resistance to conventional treatments; in contrast, the combination of tubacin and bortezomib triggers toxicity even in adherent MM cells. Our studies therefore demonstrate that tubacin combined with bortezomib mediates significant anti-MM activity, providing the framework for clinical evaluation of combined therapy to improve patient outcome in MM. C1 MIT, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Chem Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Schreiber, SL (reprint author), MIT, 320 Charles St, Cambridge, MA 02141 USA. EM stuart_schreiber@harvard.edu FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947, R01 CA050947]; NHLBI NIH HHS [T32 HL007623, T32-HL07623-18]; PHS HHS [P0-1 78378, 38627] NR 29 TC 364 Z9 377 U1 2 U2 16 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 JUN 14 PY 2005 VL 102 IS 24 BP 8567 EP 8572 DI 10.1073/pnas.0503221102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200032 PM 15937109 ER PT J AU Johannessen, CM Reczek, EE James, MF Brems, H Legius, E Cichowski, K AF Johannessen, CM Reczek, EE James, MF Brems, H Legius, E Cichowski, K TI The NF1 tumor suppressor critically regulates TSC2 and mTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neurofibromin; Ras ID TUBEROUS SCLEROSIS COMPLEX; SCHWANN-CELLS; NEUROFIBROMATOSIS TYPE-1; KINASE-ACTIVITY; RAPAMYCIN TOR; DIRECT TARGET; GROWTH-FACTOR; S6 KINASE; PATHWAY; ACTIVATION AB Loss-of-function mutations in the NF1 tumor suppressor gene underlie the familial cancer syndrome neurofibromatosis type I (NF1). The NF1-encoded protein, neurofibromin, functions as a Ras-GTPase activating protein (RasGAP). Accordingly, deregulation of Ras is thought to contribute to NF1 development. However, the critical effector pathways involved in disease pathogenesis are still unknown. We show here that the mTOR pathway is tightly regulated by neurofibromin. mTOR is constitutively activated in both NF1-deficient primary cells and human tumors in the absence of growth factors. This aberrant activation depends on Ras and P13 kinase, and is mediated by the phosphorylation and inactivation of the TSC2-encoded protein tuberin by AKT. Importantly, tumor cell lines derived from NF1 patients, and a genetically engineered cell system that requires Nf1-deficiency for transformation, are highly sensitive to the mTOR inhibitor rapamycin. Furthermore, while we show that the activation of endogenous Ras leads to constitutive mTOR signaling in this disease state, we also demonstrate that in normal cells Ras is differentially required for mTOR signaling in response to various growth factors. Thus, these findings identify the NF1 tumor suppressor as an indispensable regulator of TSC2 and mTOR. Furthermore, our results also demonstrate that Ras plays a critical role in the activation of mTOR in both normal and tumorigenic settings. Finally, these data suggest that rapamycin, or its derivatives, may represent a viable therapy for NF1. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Catholic Univ Louvain, Univ Hosp, Ctr Human Genet, B-3000 Louvain, Belgium. RP Cichowski, K (reprint author), Harvard Univ, Sch Med, 458c NRB,77 Louis Pasteur Ave, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu FU NINDS NIH HHS [NS24279, P01 NS024279] NR 45 TC 302 Z9 309 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8573 EP 8578 DI 10.1073/pnas.0503224102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200033 PM 15937108 ER PT J AU Miller, MM Wang, C Parisini, E Coletta, RD Goto, RM Lee, SY Barral, DC Townes, M Roura-Mir, C Ford, HL Brenner, MB Dascher, CC AF Miller, MM Wang, C Parisini, E Coletta, RD Goto, RM Lee, SY Barral, DC Townes, M Roura-Mir, C Ford, HL Brenner, MB Dascher, CC TI Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen presentation; comparative immunology/evolution; cell surface molecules ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II GENES; B-COMPLEX; VERTEBRATE EVOLUTION; ANTIGEN PRESENTATION; NUCLEOLAR ORGANIZER; RFP-Y; CHICKEN; CELLS; DUPLICATION AB Many of the genes that comprise the vertebrate adaptive immune system are conserved across wide evolutionary time scales. Most notably, homologs of the mammalian MHC gene family have been found in virtually all jawed vertebrates, including sharks, bony fishes, reptiles, and birds. The CD1 family of antigen-presenting molecules are related to the MHC class I family but have evolved to bind and present lipid antigens to T cells. Here, we describe two highly divergent nonclassical MHC class I genes found in the chicken (Gallus gallus) that have sequence homology to the mammalian CD1 family of proteins. one of the chicken CD1 genes expresses a full-length transcript, whereas the other has multiple splice variants. Both Southern blot and single nucleotide polymorphism analysis indicates that chicken CD1 is relatively nonpolymorphic. Moreover, cross-hybridizing bands are present in other bird species, suggesting broad conservation in the avian class. Northern analysis of chicken tissue shows a high level of CD1 expression in the bursa and spleen. In addition, molecular modeling predicts that the potential antigen-binding pocket is probably hydrophobic, a universal characteristic of CD1 molecules. Genomic analysis indicates that the CD1 genes are located on chicken chromosome 16 and maps to within 200 kb of the chicken MHC B locus, suggesting that CD1 genes diverged from classical MHC genes while still linked to the major histocompatibility complex locus. The existence of CD1 genes in an avian species suggests that the origin of CD1 extends deep into the evolutionary history of terrestrial vertebrates. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Biol, Duarte, CA 91010 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Dascher, CC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith 516C,1 Jimmy Fund Way, Boston, MA 02115 USA. EM cdascher@rics.bwh.harvard.edu RI Barral, Duarte/E-7548-2013; Roura-Mir, Carme/D-4538-2013; Coletta, Ricardo/B-4909-2015 OI Barral, Duarte/0000-0001-8867-2407; Roura-Mir, Carme/0000-0003-0514-337X; Coletta, Ricardo/0000-0001-5285-3046 FU NCI NIH HHS [SR21CA105425] NR 37 TC 72 Z9 74 U1 4 U2 14 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 JUN 14 PY 2005 VL 102 IS 24 BP 8674 EP 8679 DI 10.1073/pnas.0500105102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200050 PM 15939884 ER PT J AU Shekelle, PG Delitto, AM AF Shekelle, PG Delitto, AM TI Treating low back pain SO LANCET LA English DT Editorial Material ID THERAPY C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Shekelle, PG (reprint author), Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. EM shekelle@rand.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 11 PY 2005 VL 365 IS 9476 BP 1987 EP 1989 DI 10.1016/S0140-6736(05)66676-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 934IB UT WOS:000229701400006 PM 15950702 ER PT J AU Parodi, K Crespo, P Eickhoff, H Haberer, T Pawelke, J Schardt, D Enghardt, W AF Parodi, K Crespo, P Eickhoff, H Haberer, T Pawelke, J Schardt, D Enghardt, W TI Random coincidences during in-beam PET measurements at microbunched therapeutic ion beams SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE positron emission tomography; random correction; carbon ion therapy ID POSITRON-EMISSION-TOMOGRAPHY; TUMOR-THERAPY; SYSTEM AB At the experimental carbon ion tumour therapy facility at GSI Darmstadt, in-beam positron emission tomography (PET) is used to monitor the dose delivery precision. A dual head positron camera has been assembled from Commercial detector components in order to measure the beta(+)-activity. induced by (fie irradiation, simultaneously it) the dose application. Despite the positive clinical impact, the image quality is limited by the low counting statistics, orders of magnitude below that in standard PET applications to nuclear medicine, This paper investigates the origin for the noisy acquisition during particle extraction from the synchrotron or GSI. The results demonstrate the failure of standard random correction techniques due to gamma-ray background correlated in time with the carbon ion beam microstructure, This prevents the use of data acquired during beam extraction for imaging, The loss Of Counting Statistics is expected to rise further at the future hospital-based facility at Heidelberg, due to a more efficient utilisation of file accelerator resulting in shorter beam pauses and a reduced treatment time. In this respect, this paper provides the basis for it new data acquisition concept tailored to the unconventional application of in-beam PET imaging to therapy monitoring at radiofrequency pulsed radiation sources. (c) 2005 Elsevier B.V. All rights reserved. C1 Forschungszentrum Rossendorf EV, Inst Nucl & Hadron Phys, D-01314 Dresden, Germany. Gesell Schwerionenforsch mbH, D-64291 Darmstadt, Germany. RP Parodi, K (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM kparodi@partners.org RI Schardt, Dieter/M-1517-2014; OI Schardt, Dieter/0000-0001-7851-5993; Crespo, Paulo/0000-0002-0891-032X NR 13 TC 27 Z9 27 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JUN 11 PY 2005 VL 545 IS 1-2 BP 446 EP 458 DI 10.1016/j.nima.2005.02.002 PG 13 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 937UA UT WOS:000229950000041 ER PT J AU Maecker, B von Bergwelt-Baildon, MS Sherr, DH Nadler, LM Schultze, JL AF Maecker, B von Bergwelt-Baildon, MS Sherr, DH Nadler, LM Schultze, JL TI Identification of a new HLA-A*0201-restricted cryptic epitope from CYP1B1 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE CYP1B1; epitope; cryptic; tumor antigen; immunotherapy ID CYTOTOXIC T-LYMPHOCYTES; ANTIGEN; TOLERANCE; IMMUNOTHERAPY; CELLS; IMMUNODOMINANT; INDUCTION; EFFICIENT AB Cytochrome P450 1B1 (CYP1B1) was recently shown to be a candidate tumor antigen broadly expressed in solid and hematologic malignancies. Nevertheless, use of such self-antigens as targets for immune intervention can be limited because of loss of high-avidity T cells during negative selection in the thymus. Recent data suggest that targeting of cryptic epitopes may represent a way to circumvent such self-tolerance and induce efficient antitumor CTL responses. Here, we present the identification and characterization of a novel, cryptic HLA-A*0201-binding peptide from CYP1B1. The nanomer CYP246 was identified by epitope deduction using algorithms to predict HLA-A*0201-binding peptides. CYP246 is characterized by strong initial HLA-A*0201 binding but a short MHC/peptide binding half-life. Expansion of high-avidity CTL was readily possible using autologous CD40-activated B cells from normal donors and cancer patients as antigen-presenting cells, suggesting that an intact T-cell repertoire can be expanded for this epitope. Lysis of CYP1B1-expressing, HLA-A*0201(+) tumor cell lines and primary tumor cells confirmed that sufficient levels of CYP246 are presented by tumor cells for effector CTL killing. These findings indicate that CYP246 is a candidate cryptic epitope for immune interventions in which tumor CYP1B1 is targeted. (c) 2005 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany. Univ Cologne, Clin Internal Med 1, Cologne, Germany. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. RP Schultze, JL (reprint author), Univ Cologne, Dept Hematol Oncol, Joseph Stelzmann Str 9,Haus 16, D-50924 Cologne, Germany. EM joachim.schultze@medizin.uni-koeln.de RI Schultze, Joachim/D-7794-2011; OI Schultze, Joachim/0000-0003-2812-9853; Sherr, David/0000-0003-3353-0553 FU NCI NIH HHS [P01-CA-66996, P01-CA-78378]; NHLBI NIH HHS [P01-HL-68705]; NIEHS NIH HHS [P01-ES-11624, R01-ES-06086] NR 19 TC 17 Z9 17 U1 0 U2 0 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 JUN 10 PY 2005 VL 115 IS 2 BP 333 EP 336 DI 10.1002/ijc.20906 PG 4 WC Oncology SC Oncology GA 920ZJ UT WOS:000228733700023 PM 15688394 ER PT J AU Samuelson, AV Narita, M Chan, HM Jin, JP de Stanchina, E McCurrach, ME Narita, M Fuchs, M Livingston, DM Lowe, SW AF Samuelson, AV Narita, M Chan, HM Jin, JP de Stanchina, E McCurrach, ME Narita, M Fuchs, M Livingston, DM Lowe, SW TI p400 is required for E1A to promote apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE ACETYLASE COMPLEX; ARF TUMOR-SUPPRESSOR; REGULATES P53-DEPENDENT APOPTOSIS; REGION 1A PROTEINS; ONCOGENIC TRANSFORMATION; TRANSCRIPTIONAL ADAPTER; P300 BINDING; DNA-DAMAGE; IN-VIVO; C-MYC AB The adenovirus E1A oncoprotein promotes proliferation and transformation by binding cellular proteins, including members of the retinoblastoma protein family, the p300/CREB-binding protein transcriptional coactivators, and the p400-TRRAP chromatin-remodeling complex. E1A also promotes apoptosis, in part, by engaging the ARF-p53 tumor suppressor pathway. We show that E1A induces ARF and p53 and promotes apoptosis in normal fibroblasts by physically associating with the retinoblastoma protein and a p400-TRRAP complex and that its interaction with p300 is largely dispensable for these effects. We further show that E1A increases p400 expression and, conversely, that suppression of p400 using stable RNA interference reduces the levels of ARF, p53, and apoptosis in E1A-expressing cells. Therefore, whereas E1A inactivates the retinoblastoma protein, it requires p400 to efficiently promote cell death. These results identify p400 as a regulator of the ARF-p53 pathway and a component of the cellular machinery that couples proliferation to cell death. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lowe, SW (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA. EM lowe@cshl.org FU NCI NIH HHS [CA 13106, P30 CA008748] NR 66 TC 41 Z9 43 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 JUN 10 PY 2005 VL 280 IS 23 BP 21915 EP 21923 DI 10.1074/jbc.M414564200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932MN UT WOS:000229557900032 PM 15741165 ER PT J AU Chao, W Shen, Y Zhu, XS Zhao, HL Novikov, M Schmidt, U Rosenzweig, A AF Chao, W Shen, Y Zhu, XS Zhao, HL Novikov, M Schmidt, U Rosenzweig, A TI Lipopolysaccharide improves cardiomyocyte survival and function after serum deprivation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; ISCHEMIA-REPERFUSION INJURY; RECEPTOR-ASSOCIATED KINASE; TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; ACUTE MYOCARDIAL-INFARCTION; NITRIC-OXIDE SYNTHASE; APOPTOTIC CELL-DEATH; HEAT-SHOCK PROTEINS; BACTERIAL LIPOPOLYSACCHARIDE AB Toll-like receptor-4 ( TLR4) and its signaling molecule interleukin-1 receptor-associated kinase (IRAK-1) play an important role in host defense and tissue inflammation. Intriguingly, systemic administration of lipopolysaccharide (LPS), the agonist for TLR4, confers a cardio-protective effect against ischemic injury. However, the mechanisms leading to the cardiac protection remain largely unknown. The present study was designed to investigate the role of TLR4 activation by LPS in protecting cardiomyocytes (CM) against apoptosis in an in vitro model of ischemia and to explore the downstream mechanisms leading to the protective effect. Incubation with LPS led to activation of IRAK-1 and protected CMs against serum deprivation (SD)induced apoptosis as demonstrated by DNA laddering, histone-DNA fragment enzyme-linked immunosorbent assay, and activation of caspase-3. Phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, and Iκ B kinase β appear to contribute to the antiapoptotic effect of LPS since the specific inhibitors, wortmannin, PD98059, and dominant negative IKKβ transgene expression reversed the LPS effect. To assess whether LPS improves CM function, we examined intracellular Ca2+ transients and cell shortening in single adult rat CMs. SD for 6 h dramatically inhibited Ca2+ transients and CM contractility. LPS at 500 ng/ml significantly improved the [Ca2+](i) transients and enhanced contractility in control CMs as well as in CMs subjected to SD. Importantly, transient ischemia led to rapid activation of IRAK-1 in cultured CMs and in adult rat myocardium. Adenovirus-mediated transgene expression of IRAK-1 but not its kinase-deficient mutant IRAK-1( K239S) protected CMs against SD-induced apoptosis. Taken together, these data suggest an important role of TLR4 signaling via IRAK-1 in protecting against SD-induced apoptosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, Charlestown, MA 02139 USA. RP Chao, W (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 4,Rm 462,55 Fruit St, Boston, MA 02114 USA. EM wchao@partners.org FU NHLBI NIH HHS [HL 04336, HL 61557] NR 68 TC 46 Z9 47 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 JUN 10 PY 2005 VL 280 IS 23 BP 21997 EP 22005 DI 10.1074/jbc.M413676200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932MN UT WOS:000229557900042 PM 15793310 ER PT J AU Benevolenskaya, EV Murray, HL Branton, P Young, RA Kaelin, WG AF Benevolenskaya, EV Murray, HL Branton, P Young, RA Kaelin, WG TI Binding of pRB to the PHD protein RBP2 promotes cellular differentiation SO MOLECULAR CELL LA English DT Article ID RETINOBLASTOMA TUMOR-SUPPRESSOR; POLYMERASE-I TRANSCRIPTION; GENE-PRODUCT; DROSOPHILA-MELANOGASTER; MAMMALIAN-CELLS; LIVING CELLS; HUMAN CANCER; S-PHASE; EXPRESSION; RECOGNITION AB pRB can enforce a G1 block by repressing E2F-responsive promoters. It also coactivates certain non-E2F transcription factors and promotes differentiation. Some pRB variants activate transcription and promote differentiation despite impaired E2F binding and transcriptional repression capabilities. We identified RBP2 in a screen for proteins that bind to such pRB variants. RBP2 resembles other chromatin-associated transcriptional regulators and RBP2 binding tracked with pRB's ability to activate transcription and promote differentiation. RBP2 and pRB colocalize and pRB/RBP2 complexes were detected in chromatin isolated from differentiating cells. RBP2 siRNA phenocopied restoration of pRB function in coactivation and differentiation assays, suggesting that pRB prevents RBP2 from repressing genes required for differentiation. In addition, two bromodomain-containing proteins were identified as RBP2 targets that are transcriptionally activated by pRB in an RBP2-dependent manner. Our results suggest that promotion of differentiation by pRB involves neutralization of free RBP2 and transcriptional activation of RBP2 targets linked to euchromatin maintenance. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 NR 56 TC 132 Z9 139 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 10 PY 2005 VL 18 IS 6 BP 623 EP 635 DI 10.1016/j.molcel.2005.05.012 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 935YB UT WOS:000229818200005 PM 15949438 ER PT J AU Bix, M Kim, S Rao, A AF Bix, M Kim, S Rao, A TI Opposites attract in differentiating T cells SO SCIENCE LA English DT Editorial Material ID LOCUS-CONTROL REGION; RANGE INTRACHROMOSOMAL INTERACTIONS; TH2 CYTOKINE LOCUS; ENHANCER; BET C1 Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Bix, M (reprint author), Univ Washington, Sch Med, Dept Immunol, 1959 NE Pacific St,HSC I6071, Seattle, WA 98195 USA. EM arao@cbr.med.harvard.edu OI Bix, Mark/0000-0003-4617-0497 FU NHLBI NIH HHS [P01 HL67664]; NIAID NIH HHS [R01 AI48636, R01 AI44432] NR 16 TC 4 Z9 4 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 JUN 10 PY 2005 VL 308 IS 5728 BP 1563 EP 1565 DI 10.1126/science.1114167 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 936BH UT WOS:000229827000030 PM 15947163 ER PT J AU Skeiky, YAW Alderson, MR Ovendale, PJ Lobet, Y Dalemans, W Orme, IM Reed, SG Campos-Neto, A AF Skeiky, YAW Alderson, MR Ovendale, PJ Lobet, Y Dalemans, W Orme, IM Reed, SG Campos-Neto, A TI Protection of mice and guinea pigs against tuberculosis induced by immunization with a single Mycobacterium tuberculosis recombinant antigen, MTB41 SO VACCINE LA English DT Article DE Mycobacterium tuberculosis; vaccine; CD4(+) T cells; CD8(+) T cells; recombinant antigen ID BACILLUS-CALMETTE-GUERIN; IMMUNE-RESPONSES; DNA VACCINE; PULMONARY TUBERCULOSIS; EXTRACELLULAR PROTEINS; CLINICAL-FEATURES; IFN-GAMMA; INFECTION; EFFICACY; IMMUNOGENICITY AB MTB41 is a mycobacterium antigen that is recognized by CD4(+) T cells early after experimental infection of mice with Mycobacterium tuberculosis and by PBMC from healthy PPD positive individuals. Immunization of mice with plasmid DNA encoding the MTB41 gene sequence results in the development of antigen-specific CD4(+) and CD8(+) T cells, and protection against challenge with virulent M. tuberculosis. In the present studies, in contrast to DNA immunization, we show, that a strong MTB41-specific CD4(+) T cell response, but no MHC class I restricted cytotoxic T lymphocyte (CTL) activity is detected in the spleen cells of infected mice. Therefore, this data suggests that the induction of CD8(+) T cell response to MTB41 epitopes by DNA immunization may not be relevant to protection because these epitopes are not recognized during the infectious process. We also compared the repertoire of rMTB41 epitope recognition by CD4(+) T cells of M. tuberculosis-infected mice with the recognition repertoire of mice immunized with the recombinant rMTB41 protein. Both regimens of sensitization lead to the recognition of the same molecular epitope. Coincidentally, immunization with the soluble recombinant protein plus adjuvant, a regimen known to generate primarily CD4(+) T cells, resulted in induction of protection comparable to BCG in two well-established animal models of tuberculosis (mice and guinea pigs). (c) 2005 Elsevier Ltd. All rights reserved. C1 Forsyth Inst, Boston, MA 02115 USA. Corixa Corp, Seattle, WA USA. GlaxoSmithKline Biol, Rixensart, Belgium. Colorado State Univ, Ft Collins, CO 80523 USA. Infect Dis Res Inst, Seattle, WA USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org FU NIAID NIH HHS [AI 43528, AI-45707, AI 44373] NR 52 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 10 PY 2005 VL 23 IS 30 BP 3937 EP 3945 DI 10.1016/j.vaccine.2005.03.003 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 936GR UT WOS:000229844000009 PM 15917115 ER PT J AU Siegert, S Bahn, E Kramer, ML Schulz-Schaeffer, WJ Hewett, JW Breakefield, XO Hedreen, JC Rostasy, KM AF Siegert, S Bahn, E Kramer, ML Schulz-Schaeffer, WJ Hewett, JW Breakefield, XO Hedreen, JC Rostasy, KM TI TorsinA expression is detectable in human infants as young as 4 weeks old SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE torsinA; brain; children; neurons; development; dopaminergic ID DYT1 DYSTONIA; HUMAN BRAIN; NUCLEAR-ENVELOPE; ALPHA-SYNUCLEIN; MUTANT TORSINA; LEWY BODIES; PC12 CELLS; ONSET; PROTEIN; LOCALIZATION AB Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein and its message has been described previously in several regions of normal adult human and rodent brain. This study examines the expression of torsinA in the developing human brain of fetuses, infants and children up to 7 years of age in four selected brain regions. Expression of torsinA protein was detectable beginning at 4 to 8 weeks of age postnatally in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia. Prominent torsinA immunoreactivity was not seen before 6 weeks of age postnatally, a period associated with synaptic remodeling, process elimination and the beginning of myelination. Our results, indicate that torsinA protein expression is temporally and spatially regulated and is present in all brain regions studied by the age of 2 months on into adulthood. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Gottingen, Dept Pediat & Pediat Neurol, D-37073 Gottingen, Germany. Univ Gottingen, Dept Neuropathol, D-3400 Gottingen, Germany. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02129 USA. Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. RP Rostasy, KM (reprint author), Univ Gottingen, Dept Pediat & Pediat Neurol, Robert Koch Str 40, D-37073 Gottingen, Germany. EM krostasy@excite.com NR 32 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUN 9 PY 2005 VL 157 IS 1 BP 19 EP 26 DI 10.1016/j.devbrainres.2005.02.019 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 939IE UT WOS:000230065200003 ER PT J AU Lu, J Getz, G Miska, EA Alvarez-Saavedra, E Lamb, J Peck, D Sweet-Cordero, A Ebet, BL Mak, RH Ferrando, AA Downing, JR Jacks, T Horvitz, HR Golub, TR AF Lu, J Getz, G Miska, EA Alvarez-Saavedra, E Lamb, J Peck, D Sweet-Cordero, A Ebet, BL Mak, RH Ferrando, AA Downing, JR Jacks, T Horvitz, HR Golub, TR TI MicroRNA expression profiles classify human cancers SO NATURE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; STEM-CELLS; SIGNATURES; RNA; DIFFERENTIATION; IDENTIFICATION; ACCUMULATION; MICROARRAYS AB Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs ( miRNAs), which have critical functions across various biological processes(1,2). Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis. C1 MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Golub, TR (reprint author), MIT, Broad Inst, Cambridge, MA 02141 USA. EM golub@broad.mit.edu RI Ferrando, Adolfo /Q-7026-2016; OI Miska, Eric/0000-0002-4450-576X NR 30 TC 5141 Z9 5547 U1 112 U2 832 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 9 PY 2005 VL 435 IS 7043 BP 834 EP 838 DI 10.1038/nature03702 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933NK UT WOS:000229638700054 PM 15944708 ER PT J AU Medoff, BD Shepard, JO Smith, RN Kratz, A AF Medoff, BD Shepard, JO Smith, RN Kratz, A TI A 22-year-old woman with back and leg pain and respiratory failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SICKLE-CELL-DISEASE; ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; ACUTE CHEST SYNDROME; EXTRACORPOREAL MEMBRANE-OXYGENATION; DISTRESS-SYNDROME; PULMONARY-HYPERTENSION; RECRUITMENT MANEUVER; COMPUTED-TOMOGRAPHY; PATIENT C1 Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 33 TC 4 Z9 4 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 JUN 9 PY 2005 VL 352 IS 23 BP 2425 EP 2434 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 933NL UT WOS:000229638900011 PM 15944428 ER PT J AU Blacker, D AF Blacker, D TI Mild cognitive impairment - No benefit from vitamin E, little from donepezil. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; CONTROLLED-TRIAL; SUPPLEMENTATION C1 Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Blacker, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. FU NIA NIH HHS [P01 AG4853] NR 18 TC 20 Z9 21 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 JUN 9 PY 2005 VL 352 IS 23 BP 2439 EP 2441 DI 10.1056/NEJMe058086 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 933NL UT WOS:000229638900013 PM 15829528 ER PT J AU Eisen, SA Kang, HK Murphy, FM Blanchard, MS Reda, DJ Henderson, WG Toomey, R Jackson, LW Alpem, R Parks, BJ Klimas, N Hall, C Pak, HS Hunter, J Karlinsky, J Battistone, MJ Lyons, MJ AF Eisen, SA Kang, HK Murphy, FM Blanchard, MS Reda, DJ Henderson, WG Toomey, R Jackson, LW Alpem, R Parks, BJ Klimas, N Hall, C Pak, HS Hunter, J Karlinsky, J Battistone, MJ Lyons, MJ CA Gulf War Study Participating Inves TI Gulf war veterans' health: Medical evaluation of a US cohort SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; POPULATION-BASED SURVEY; OPERATION-DESERT-STORM; AL ESKAN DISEASE; VISCERAL INFECTION; LEISHMANIA-TROPICA; ILLNESS; FIBROMYALGIA; PREVALENCE; ACTIVATION AB Background: United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms' long-term prevalence and association with deployment remain controversial. Objective: To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations. Design: A cross-sectional prevalence study performed 10 years after the 1991 Gulf War. Setting: Veterans were examined at 1 of 16 Veterans Affairs medical centers. Participants: Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War. Measurements: Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health-related quality of life (Short Form-36 [SF36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy. Results: Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% Cl, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [Cl, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [Cl, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [Cl, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively. Limitations: Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected. Conclusions: Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score. C1 Washington Univ, Sch Med, Med Affairs Med Ctr 151 JC, St Louis, MO 63103 USA. St Louis Univ, St Louis, MO 63103 USA. US Dept Vet Affairs, Vet Hlth Adm, Environm Epidemiol Serv, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Washington, DC USA. Hines Vet Affairs Hosp, Cooperat Studies Program, Coodinating Ctr, Hines, IL USA. Harvard Univ, Vet Affairs Med Ctr, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Vet Affairs Med Ctr, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Vet Affairs Med Ctr, Miami, FL 33125 USA. Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. RP Eisen, SA (reprint author), Washington Univ, Sch Med, Med Affairs Med Ctr 151 JC, 915 N Grand Ave, St Louis, MO 63103 USA. EM seth.eisen@med.va.gov RI Lyons, Michael/B-6119-2011 NR 50 TC 61 Z9 63 U1 1 U2 4 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 JUN 7 PY 2005 VL 142 IS 11 BP 881 EP 890 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 932LX UT WOS:000229556300001 PM 15941694 ER PT J AU O'Neill, MS Veves, A Zanobetti, A Sarnat, JA Gold, DR Economides, PA Horton, ES Schwartz, J AF O'Neill, MS Veves, A Zanobetti, A Sarnat, JA Gold, DR Economides, PA Horton, ES Schwartz, J TI Diabetes enhances vulnerability to particulate air pollution - Associated impairment in vascular reactivity and endothelial function SO CIRCULATION LA English DT Article DE diabetes mellitus; endothelium; epidemiology; pollution; vasculature ID FLOW-MEDIATED VASODILATION; HEALTHY-HUMAN VOLUNTEERS; CORONARY-ARTERY-DISEASE; HEART-DISEASE; METROPOLITAN PHILADELPHIA; PERSONAL PARTICULATE; ULTRAFINE PARTICLES; CARDIOVASCULAR RISK; SPATIAL VARIATION; OXIDATIVE STRESS AB Background-Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes. Methods and Results-Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution ( fine particles [PM2.5], particle number, black carbon, and sulfates [SO42-]) &AP; 500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter ( flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO42- were associated with decreased flow-mediated (-10.7%; 95% CI, -17.3 to -3.5) and nitroglycerin-mediated (-5.4%; 95% CI, -10.5 to -0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity ( -12.6%; 95% CI, -21.7 to -2.4), and PM2.5 was associated with nitroglycerin-mediated reactivity ( -7.6%; 95% CI, -12.8 to -2.1). Effects were stronger in type II than type I diabetes. Conclusions-Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP O'Neill, MS (reprint author), Robert Wood Johnson Hlth & Soc Scholar, Dept Epidemiol, 1214 S Univ Ave,Room 249, Ann Arbor, MI 48104 USA. EM marieo@umich.edu FU NCRR NIH HHS [RR 01032]; NIDDK NIH HHS [2P30-DK-36836]; NIEHS NIH HHS [2 T32 ES07069-24, ES00002, P01 ES009825] NR 58 TC 259 Z9 267 U1 2 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 7 PY 2005 VL 111 IS 22 BP 2913 EP 2920 DI 10.1161/CIRCULATIONAHA.104.517110 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 933CD UT WOS:000229600700009 PM 15927967 ER PT J AU Masutomi, K Possemato, R Wong, JMY Currier, JL Tothova, Z Manola, JB Ganesan, S Lansdorp, PM Collins, K Hahn, WC AF Masutomi, K Possemato, R Wong, JMY Currier, JL Tothova, Z Manola, JB Ganesan, S Lansdorp, PM Collins, K Hahn, WC TI The telomerase reverse transcriptase regulates chromatin state and DNA damage responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human telomerase reverse transcriptase; histone modification; genomic integrity ID NORMAL HUMAN-CELLS; REPLICATIVE LIFE-SPAN; DOUBLE-STRAND BREAKS; CATALYTIC SUBUNIT; IN-VIVO; CELLULAR SENESCENCE; IONIZING-RADIATION; ENZYME-ACTIVITY; HETEROCHROMATIN; CANCER AB Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells and also contributes to transformation independently of net telomere elongation. Here, we show that suppression of the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] expression abrogates the cellular response to DNA double strand breaks. Loss of hTERT does not alter short-term telomere integrity but instead affects the overall configuration of chromatin. Cells lacking hTERT exhibit increased radiosensitivity, diminished capacity for DNA repair, and fragmented chromosomes, demonstrating that loss of hTERT impairs the DNA damage response. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ British Columbia, British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu OI Wong, Judy/0000-0001-5572-4143; Possemato, Richard/0000-0002-2401-0030 FU NCI NIH HHS [K01 CA094223, K01 CA94223]; NIA NIH HHS [R01 AG023145, R01AG023145] NR 43 TC 183 Z9 193 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 2005 VL 102 IS 23 BP 8222 EP 8227 DI 10.1073/pnas.0503095102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500028 PM 15928077 ER PT J AU Gold, PW Wong, ML Goldstein, DS Gold, HK Ronsaville, DS Esler, M Alesci, S Masood, A Licinio, J Geracioti, TD Perini, G Debellis, MD Holmes, C Vgontzas, AN Charney, DS Chrousos, GP McCann, SM Kling, MA AF Gold, PW Wong, ML Goldstein, DS Gold, HK Ronsaville, DS Esler, M Alesci, S Masood, A Licinio, J Geracioti, TD Perini, G Debellis, MD Holmes, C Vgontzas, AN Charney, DS Chrousos, GP McCann, SM Kling, MA TI Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebrospinal fluid; epinephrine; major depression; cardiovascular disease; chronic heart failure ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; PLASMA NOREPINEPHRINE; SYMPATHETIC ACTIVITY; MAJOR DEPRESSION; SYSTEM; ACTIVATION; MORTALITY; SYMPTOMS; KINETICS AB The mortality of chronic heart failure (CHIF) doubles either when CHIF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by approximate to 40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHIF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed basal and stress-mediated arterial NE appearance. Severely depressed patients had significant increases in mean around-the-clock levels of CSIF NE (P < 0.02), plasma NE (P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF NE, plasma NE, and cortisol all rose together throughout the night and peaked in the morning. Each fell to control values after ECT. Mildly-to-moderately melancholic patients also had increased basal (P < 0.05) and stress-related (P < 0.03) arterial NE-appearance rates. Severely melancholic depressed, medication-free patients had around-the-clock increases in plasma NE levels capable of increasing mortality in CHF. Twenty-four-hour indices of central noradrenergic, adrenomedullary, and adrenocortical secretion were also elevated. Concurrent diurnal rhythms of these secretions could potentiate their cardiotoxicity. Even mildly-to-moderately depressed melancholic patients had clinically relevant increases in the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Inst Neuropsychiat, Los Angeles, CA 90095 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Baker Heart Res Inst, Melbourne, Vic 8008, Australia. Univ Cincinnati, Sch Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Padua, Dept Neurol & Psychiat Sci, I-35122 Padua, Italy. Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27708 USA. Penn State Univ, Dept Psychiat, Hershey, PA 17033 USA. CUNY Mt Sinai Sch Med, Deans Off, New York, NY 10029 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. EM philipgold@mail.nih.gov RI Kling, Mitchel/F-4152-2010; Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013; OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884; PERINI, GIULIA/0000-0003-3261-1984 NR 25 TC 55 Z9 57 U1 2 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 JUN 7 PY 2005 VL 102 IS 23 BP 8303 EP 8308 DI 10.1073/pnas.0503069102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500042 PM 15919819 ER PT J AU Mann, DL AF Mann, DL TI Targeted anticytokine therapy and the failing heart SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Immue Activation and Inflammation in Chronic Heart Failure CY NOV 17, 2002 CL Chicago, IL ID TUMOR-NECROSIS-FACTOR; LEFT-VENTRICULAR DYSFUNCTION; FC FUSION PROTEIN; FACTOR-ALPHA; DILATED CARDIOMYOPATHY; TNF-ALPHA; MONOCLONAL-ANTIBODY; EJECTION FRACTION; SOLUBLE RECEPTORS; CYTOKINE LEVELS AB Recent studies have identified the importance of proinflammatory mediators in the development and progression of chronic heart failure (CHF). The growing appreciation of the pathophysiologic consequences of sustained expression of proinflammatory mediators in preclinical and clinical CHF models culminated in a series of multicenter clinical trials that used targeted approaches to neutralize tumor necrosis factor in patients with moderate-to-advanced CHF. However, these targeted approaches have resulted in worsening CHF, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of CHF. This review summarizes what has been learned from the negative clinical trials, as well as the potential direction of future research in this area. (c) 2005 by Excerpta Medica Inc. C1 Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Michael E DeBakey Vet Adm Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist DeBakey Heart Ctr, Houston, TX USA. RP Mann, DL (reprint author), Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Michael E DeBakey Vet Adm Med Ctr, MS 524,6565 Fannin St, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL61543-01, HL-42250-10/10, R01 HL58081-01] NR 47 TC 54 Z9 57 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 6 PY 2005 VL 95 IS 11A SU S BP 9C EP 16C DI 10.1016/j.amjcard.2005.03.007 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 932ZQ UT WOS:000229593800003 PM 15925559 ER PT J AU Stier, S Ko, Y Forkert, F Lutz, C Neuhaus, T Grunewald, E Cheng, T Dombkowski, D Calvi, LM Rittling, SR Scadden, DT AF Stier, S Ko, Y Forkert, F Lutz, C Neuhaus, T Grunewald, E Cheng, T Dombkowski, D Calvi, LM Rittling, SR Scadden, DT TI Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MICE LACKING OSTEOPONTIN; IN-VITRO; BONE-MARROW; LIGAND INTERACTION; ENDOTHELIAL-CELLS; PROGENITOR CELLS; SMOOTH-MUSCLE; T-CELLS; RECEPTOR; VIVO AB Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell-nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Univ Bonn, Med Poliklin, D-53111 Bonn, Germany. Univ Rochester, Sch Med, Dept Med, Rochester, NY 14642 USA. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. RP Ko, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Regenerat Med & Technol, Boston, MA 02114 USA. EM y.ko@jk-bonn.de; scadden.david@mgh.harvard.edu OI Calvi, Laura Maria/0000-0001-6969-239X FU NCI NIH HHS [CA086355, P50 CA086355]; NHLBI NIH HHS [HL65909, HL44851, R01 HL044851, R01 HL065909]; NIDDK NIH HHS [K08 DK064381, K08 DK064381-03, R21 DK069563, R21 DK069563-01] NR 50 TC 344 Z9 364 U1 1 U2 12 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 JUN 6 PY 2005 VL 201 IS 11 BP 1781 EP 1791 DI 10.1084/jem.20041992 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 933CA UT WOS:000229600300011 PM 15928197 ER PT J AU Park, J Berthiaume, F Toner, M Yarmush, ML Tilles, AW AF Park, J Berthiaume, F Toner, M Yarmush, ML Tilles, AW TI Microfabricated grooved substrates as platforms for bioartificial liver reactors SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE bioartificial liver; microfabrication; perfusion; hepatocyte; microgrooves; bioreactor ID I CLINICAL-TRIAL; RAT HEPATOCYTES; PHASE-I; OXYGEN-TRANSFER; BIOREACTOR; CELLS; PERFUSION; FAILURE; SUPPORT; VITRO AB An extracorporeal bioartificial liver device has the potential to provide temporary hepatic support for patients with liver failure. Our goal was to optimize the flow environment for the cultured hepatocytes in a flat-plate bioreactor, specifically focusing on oxygen delivery using high medium flow rates while reducing the detrimental effects of the resulting shear stresses. We used photolithographic techniques to fabricate microgrooves onto the underlying glass substrate. The microgrooves, perpendicular to the axial flow direction, protected the hepatocytes from the shear stress induced by the flowing medium. Using finite element analysis, we found that the velocity gradient change near the cell surface (i.e., bottom of the grooves) was smaller than that near the top surface of the flow channel, indicating that the grooves would provide protection to the attached cells from the mechanical effects of the flowing medium. We also determined that the shear stress at the cell surface could be reduced by as Much as 30 times (channel 2 height of 100 gm) in the grooved-substrate (0.5 dyn/cm(2)) bioreactor compared to the flat-substrate (15 dyn/cm(2)) bioreactor for a medium flow rate of 4.0 mL/min. Albumin and urea synthesis rates of hepatocytes cocultured with 3T3-J2 fibroblasts remained stable over 5 days of perfusion in the grooved-substrate bioreactor, whereas in the flat-substrate bioreactor they decreased over the same time period. These studies indicate that under "high" flow conditions the microgrooved-substrate in the bioreactor can decrease the detrimental effects of shear stress on the hepatocytes while providing adequate oxygenation, thereby resulting in stable liver-specific function. (c) 2005 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tilles, AW (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM arno_tilles@hms.harvard.edu RI Yu, weiting/I-7417-2013 FU NIBIB NIH HHS [P41 EB002503, P41 EB02503]; NIDDK NIH HHS [K08 DK66040, R01 DK43371] NR 36 TC 88 Z9 96 U1 2 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 5 PY 2005 VL 90 IS 5 BP 632 EP 644 DI 10.1002/bit.20463 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 930LO UT WOS:000229417600012 PM 15834948 ER PT J AU Corradini, P Farina, L AF Corradini, P Farina, L TI Immune-mediated attack in relapsed Hodgkin's lymphoma SO LANCET LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; DONOR LEUKOCYTE INFUSIONS; MARROW TRANSPLANTATION; DISEASE C1 Univ Milan, Ist Nazl Studio & Cura Tumori, Dept Haematol, Milan, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Corradini, P (reprint author), Univ Milan, Ist Nazl Studio & Cura Tumori, Dept Haematol, Milan, Italy. EM paolo.corradini@istitutotumori.mi.it RI Farina, Lucia/F-3673-2017 OI Farina, Lucia/0000-0002-5219-0673 NR 11 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 4 PY 2005 VL 365 IS 9475 BP 1906 EP 1908 DI 10.1016/S0140-6736(05)66636-6 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 932XJ UT WOS:000229587800005 PM 15936404 ER PT J AU Epstein, AJ Rathore, SS Krumholz, HM Volpp, KGM AF Epstein, AJ Rathore, SS Krumholz, HM Volpp, KGM TI Volume-based referral for cardiovascular procedures in the United States: a cross-sectional regression analysis SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID BYPASS GRAFT-SURGERY; CORONARY ANGIOPLASTY VOLUME; SHORT-TERM MORTALITY; POTENTIAL BENEFITS; PATIENT MORTALITY; HOSPITALS; LEAPFROG; REGIONALIZATION; STANDARDS; CARE AB Background: We sought to estimate the numbers of patients affected and deaths avoided by adopting the Leapfrog Group's recommended hospital procedure volume minimums for coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). In addition to hospital risk-adjusted mortality standards, the Leapfrog Group recommends annual hospital procedure minimums of 450 for CABG and 400 for PCI to reduce procedure-associated mortality. Methods: We conducted a retrospective analysis of a national hospital discharge database to evaluate in-hospital mortality among patients who underwent PCI (n = 2,500,796) or CABG ( n = 1,496,937) between 1998 and 2001. We calculated the number of patients treated at low volume hospitals and simulated the number of deaths potentially averted by moving all patients to high volume hospitals under best-case conditions (i.e., assuming the full volume-associated reduction in mortality and the capacity to move all patients to high volume hospitals with no related harms). Results: Multivariate adjusted odds of in-hospital mortality were higher for patients treated in low volume hospitals compared with high volume hospitals for CABG ( OR 1.16, 95% CI 1.10 - 1.24) and PCI ( OR 1.12, 95% CI 1.05 - 1.20). A policy of hospital volume minimums would have required moving 143,687 patients for CABG and 87,661 patients for PCI from low volume to high volume hospitals annually and prevented an estimated 619 CABG deaths and 109 PCI deaths. Thus, preventing a single death would have required moving 232 CABG patients or 805 PCI patients from low volume to high volume hospitals. Conclusion: Recommended hospital CABG and PCI volume minimums would prevent 728 deaths annually in the United States, fewer than previously estimated. It is unclear whether a policy requiring the movement of large numbers of patients to avoid relatively few deaths is feasible or effective. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. Philadelphia Vet Affairs Hosp, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Gen Internal Med Sect, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch Business, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. RP Epstein, AJ (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06510 USA. EM andrew.epstein@yale.edu; saif.rathore@yale.edu; harlan.krumholz@yale.edu; volpp70@mail.med.upenn.edu FU AHRQ HHS [T32-HS00009, T32 HS000009]; NIGMS NIH HHS [GM07205, T32 GM007205] NR 25 TC 21 Z9 21 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JUN 3 PY 2005 VL 5 AR 42 DI 10.1186/1472-6963-5-42 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 945BS UT WOS:000230476700001 PM 15935099 ER PT J AU Kim, H Rhee, SH Kokkotou, E Na, X Savidge, T Moyer, MP Pothoulakis, C LaMont, JT AF Kim, H Rhee, SH Kokkotou, E Na, X Savidge, T Moyer, MP Pothoulakis, C LaMont, JT TI Clostridium difficile toxin A regulates inducible cyclooxygenase-2 and prostaglandin E-2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; COLON-CANCER CELLS; NF-KAPPA-B; MESSENGER-RNA; CHOLERA-TOXIN; TRANSCRIPTIONAL REGULATION; SIGNAL-TRANSDUCTION; RESPONSIVE ELEMENT; HYDROGEN-PEROXIDE; INDUCED ENTERITIS AB Clostridium difficile toxin A induces acute colitis with neutrophil infiltration and up-regulation of numerous pro-inflammatory mediators, but the contribution of cyclooxygenase-2 (COX-2) induction in this infection is unknown. We report here that toxin A induces expression of COX-2 and secretion of prostaglandin E2 (PGE(2)) in a dose- and time-dependent manner in cultured NCM460 human colonocytes and in human intestinal xenografts. This induction was blocked by SB203580, a p38 MAPK inhibitor, which also decreased the phosphorylation of MSK-1, CREB/ATF-1, and COX-2 promoter activity following toxin A stimulation. Gel shift assays indicated that CREB/ATF-1 was the major proteins binding to the COX-2-CRE. Moreover, colonocytes exposed to toxin A produced reactive oxygen species (ROS), which activated p38 MAPK, MSK-1, and CREB/ATF-1, leading to subsequent COX-2 induction and PGE2 secretion. In intact mice, blockage of p38 MAPK inhibited toxin A-mediated induction of COX-2 in enterocytes as well as lamina propria cells, and significantly blocked the toxin A-induced ileal secretion of fluid and PGE2. Furthermore, a selective COX-2 inhibitor also diminished toxin A-associated ileal fluid and PGE2 secretion. The main signaling pathway for toxin A induction of human COX-2 involves ROS-mediated activation of p38 MAPK, MSK-1, CREB, and ATF-1. Toxin A triggers ileal inflammation and secretion of fluid via COX-2 induction and release of PGE2. C1 Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nutr, Boston, MA 02215 USA. INCELL Corp, San Antonio, TX 78249 USA. RP LaMont, JT (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dana 501,330 Brookline Ave, Boston, MA 02215 USA. EM jlamont@bidmc.harvard.edu FU NIDDK NIH HHS [DK R01-33506, DK R37-38458] NR 52 TC 62 Z9 64 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 JUN 3 PY 2005 VL 280 IS 22 BP 21237 EP 21245 DI 10.1074/jbc.M413842200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800042 PM 15767259 ER PT J AU Paleotti, O Macia, E Luton, F Klein, S Partisani, M Chardin, P Kirchhausen, T Franco, M AF Paleotti, O Macia, E Luton, F Klein, S Partisani, M Chardin, P Kirchhausen, T Franco, M TI The small G-protein Arf6(GTP) recruits the AP-2 adaptor complex to membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; CANINE KIDNEY-CELLS; PLASMA-MEMBRANE; PHOSPHOLIPASE-D; EXCHANGE FACTOR; REGULATED EXOCYTOSIS; MEDIATED ENDOCYTOSIS; DOWNSTREAM EFFECTOR; CLATHRIN ADAPTERS; ARF6 AB The small GTP-binding protein ADP-ribosylation factor 6 (Arf6) is involved in plasma membrane/endosomes trafficking. However, precisely how the activation of Arf6 regulates vesicular transport is still unclear. Here, we show that, in vitro, recombinant Arf6GTP recruits purified clathrin-adaptor complex AP-2 (but not AP-1) onto phospholipid liposomes in the absence of phosphoinositides. We also show that phosphoinositides and Arf6 tightly cooperate to translocate AP-2 to the membrane. In vivo, Arf6GTP (but not Arf6GDP) was found associated to AP-2. The expression of the GTP-locked mutant of Arf6 leads to the plasma membrane redistribution of AP-2 in Arf6GTP-enriched areas. Finally, we demonstrated that the expression of the GTP-locked mutant of Arf6 inhibits transferrin receptor internalization without affecting its recycling. Altogether, our results demonstrated that Arf6GTP interacts specifically with AP-2 and promotes its membrane recruitment. These findings strongly suggest that Arf6 plays a major role in clathrin-mediated endocytosis by directly controlling the assembly of the AP-2/clathrin coat. C1 CNRS, Inst Pharmacol Mol & Cellulaire, UMR 6097, F-06560 Valbonne, France. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Biomed Res Inst, Boston, MA 02115 USA. RP Franco, M (reprint author), CNRS, Inst Pharmacol Mol & Cellulaire, UMR 6097, 660 Route Lucioles, F-06560 Valbonne, France. EM franco@ipmc.cnrs.fr NR 35 TC 75 Z9 77 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21661 EP 21666 DI 10.1074/jbc.m503099200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800092 PM 15802264 ER PT J AU Suh, Y Vijg, J AF Suh, Y Vijg, J TI SNP discovery in associating genetic variation with human disease phenotypes SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE single nucleotide polymorphism (SNP); association analysis; candidate pathway approach; functional variants; pre-screening methods for SNP discovery ID GRADIENT GEL-ELECTROPHORESIS; CYSTIC-FIBROSIS GENE; LINKAGE DISEQUILIBRIUM; POLYMORPHISM ANALYSIS; COMPLEX DISEASE; COMMON DISEASE; HUMAN GENOME; HAPLOTYPE VARIATION; SEQUENCE VARIATION; MUTATION DATABASE AB With the completion of the human genome project, attention is now rapidly shifting towards the study of individual Genetic variation. The most abundant source of genetic variation in the human genome is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Identification of SNPs that contribute to susceptibility to common diseases will provide highly accurate diagnostic information that will facilitate early diagnosis, prevention, and treatment of human diseases. Over the past several years, the advancement of increasingly high-throughput and cost-effective methods to discover and measure SNPs has begun to open the door towards this endeavor. Genetic association studies are considered to be an effective approach towards the detection of SNPs with moderate effects, as in most common diseases with complex phenotypes. This requires careful study design, analysis and interpretation. In this review, we discuss genetic association studies and address the prospect for candidate gene association Studies, comparing the strengths and weaknesses of indirect and direct study designs. Our focus is on the continuous need for SNP discovery methods and the use of currently available prescreening methods for large-scale Genetic epidemiological research until more advanced sequencing methods currently under development will become available. © 2005 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, Dept Physiol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Suh, Y (reprint author), Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, Dept Physiol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM suny@uthscsa.edu; vijg@uthscsa.edu FU NIA NIH HHS [R03 AG023292, AG023292, AG024391, AG17242, AG20438, R01 AG024391, R01 AG024391-01, R01 AG024391-02, R01 AG024391-03, R01 AG024391-04, R01 AG024391-05, R03 AG023292-01, R03 AG023292-02]; NIEHS NIH HHS [ES11044] NR 81 TC 110 Z9 117 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 3 PY 2005 VL 573 IS 1-2 BP 41 EP 53 DI 10.1016/j.mrfmmm.2005.01.005 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 923CX UT WOS:000228887700004 PM 15829236 ER PT J AU Newton-Cheh, C Hirschhorn, JN AF Newton-Cheh, C Hirschhorn, JN TI Genetic association studies of complex traits: design and analysis issues SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE association study; complex trait; genetics; genomics; single nucleotide polymorphism; review ID DIETARY-FAT INTAKE; HUMAN-GENOME; CROHNS-DISEASE; LINKAGE DISEQUILIBRIUM; POPULATION STRATIFICATION; TRANSMISSION/DISEQUILIBRIUM TEST; QUANTITATIVE TRAITS; HAPLOTYPE STRUCTURE; COMMON DISEASE; INSULIN GENE AB Most common diseases and many important quantitative traits are complex genetic traits, with multiple genetic and environmental variables contributing to the observed phenotype. Because of the multi-factorial nature of complex traits, each individual genetic variant generally has only a modest effect, and the interaction of genetic variants with each other or with environmental factors can potentially be quite important in determining the observed phenotype. It remains largely unknown what sort of genetic variants explain inherited variation in complex traits, but recent evidence suggests that common genetic variants will explain at least some of the inherited variation in susceptibility to common disease. Genetic association studies, in which the allele or genotype frequencies at markers are determined in affected individuals and compared with those of controls (either population- or family-based), may be an effective approach to detecting the effects of common variants with modest effects. With the explosion in single nucleotide polymorphism (SNP) discovery and genotyping technologies, large-scale association studies have become feasible, and small-scale association studies have become plentiful. We review the different types of association studies and discuss issues that are important to consider when performing and interpreting association studies of complex genetic traits. Heritable and accurately measured phenotypes, carefully matched large samples, well-chosen genetic markers, and adequate standards in genotyping, analysis, and interpretation are all integral parts of a high-quality association study. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Harvard Univ, Broad Inst, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. EM joel.hirschhorn@childrens.harvard.edu NR 84 TC 162 Z9 172 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 3 PY 2005 VL 573 IS 1-2 BP 54 EP 69 DI 10.1016/j.mrfmmm.2005.01.006 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 923CX UT WOS:000228887700005 PM 15829237 ER PT J AU Hock, H Orkin, SH AF Hock, H Orkin, SH TI Stem cells - The road not taken SO NATURE LA English DT Editorial Material ID BONE-MARROW; B-CELLS; PROGENITOR; IDENTIFICATION; LINEAGES C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Hock, H (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 11 TC 4 Z9 4 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 JUN 2 PY 2005 VL 435 IS 7042 BP 573 EP + DI 10.1038/435573a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931HK UT WOS:000229476200028 PM 15931202 ER PT J AU Sykes, M Nikolic, B AF Sykes, M Nikolic, B TI Treatment of severe autoimmune disease by stem-cell transplantation SO NATURE LA English DT Review ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; REGULATORY T-CELLS; MIXED HEMATOPOIETIC CHIMERISM; TYPE-1 DIABETES-MELLITUS; STAGE RENAL-DISEASE; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; RHEUMATOID-ARTHRITIS; MULTIPLE-MYELOMA AB Transplantation of haematopoietic stem cells - cells capable of self renewing and reconstituting all types of blood cell - can treat numerous lethal diseases, including leukaemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis. Studies in animal models show that the transfer of haematopoietic stem cells can reverse autoimmunity, and several mechanistic pathways may explain this phenomenon. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM sykes@tbrc.mgh.harvard.edu; bnikolic@partners.org NR 68 TC 127 Z9 140 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 2 PY 2005 VL 435 IS 7042 BP 620 EP 627 DI 10.1038/nature03728 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931HK UT WOS:000229476200040 PM 15931215 ER PT J AU Oltersdorf, T Elmore, SW Shoemaker, AR Armstrong, RC Augeri, DJ Belli, BA Bruncko, M Deckwerth, TL Dinges, J Hajduk, PJ Joseph, MK Kitada, S Korsmeyer, SJ Kunzer, AR Letai, A Li, C Mitten, MJ Nettesheim, DG Ng, S Nimmer, PM O'Connor, JM Oleksijew, A Petros, AM Reed, JC Shen, W Tahir, SK Thompson, CB Tomaselli, KJ Wang, BL Wendt, MD Zhang, HC Fesik, SW Rosenberg, SH AF Oltersdorf, T Elmore, SW Shoemaker, AR Armstrong, RC Augeri, DJ Belli, BA Bruncko, M Deckwerth, TL Dinges, J Hajduk, PJ Joseph, MK Kitada, S Korsmeyer, SJ Kunzer, AR Letai, A Li, C Mitten, MJ Nettesheim, DG Ng, S Nimmer, PM O'Connor, JM Oleksijew, A Petros, AM Reed, JC Shen, W Tahir, SK Thompson, CB Tomaselli, KJ Wang, BL Wendt, MD Zhang, HC Fesik, SW Rosenberg, SH TI An inhibitor of Bcl-2 family proteins induces regression of solid tumours SO NATURE LA English DT Article ID SMALL-MOLECULE INHIBITORS; CELL-DEATH; RATIONAL DESIGN; BH3 DOMAIN; APOPTOSIS; DISCOVERY; BCL-X(L); EXPRESSION; ANTISENSE; COMPOUND AB Proteins in the Bcl-2 family are central regulators of programmed cell death(1), and members that inhibit apoptosis, such as Bcl-X-L and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy(2). Bcl-X-L expression correlates with chemo-resistance of tumour cell lines(3), and reductions in Bcl-2 increase sensitivity to anticancer drugs(4) and enhance in vivo survival(5). The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored(6-15), but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein - protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X-L and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds(7-15). Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice. C1 Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA. Idun Pharmaceut, San Diego, CA 92121 USA. Burnham Inst, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Rosenberg, SH (reprint author), Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA. EM stephen.fesik@abbott.com; saul.rosenberg@abbott.com NR 30 TC 1979 Z9 2034 U1 36 U2 299 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 2 PY 2005 VL 435 IS 7042 BP 677 EP 681 DI 10.1038/nature03579 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 931HK UT WOS:000229476200051 PM 15902208 ER PT J AU Mileykovskiy, BY Kiyashchenko, LI Siegel, JM AF Mileykovskiy, BY Kiyashchenko, LI Siegel, JM TI Behavioral correlates of activity in identified hypocretin/orexin neurons SO NEURON LA English DT Article ID DORSAL RAPHE NUCLEUS; FREELY MOVING CATS; HYPOTHALAMIC AROUSAL SYSTEM; MEDIAL PREFRONTAL CORTEX; POWER SPECTRAL-ANALYSIS; SLEEP-WAKING DISCHARGE; VENTRAL TEGMENTAL AREA; OREXIN NEURONS; LOCUS-COERULEUS; RETICULAR-FORMATION AB Micropipette recording with juxtacellular Neurobiotin ejection, linked micropipette-microwire recording, and antidromic and orthodromic activation from the ventral tegmental area and locus coeruleus were used to identify hypocretin (Hcrt) cells in anesthetized rats and develop criteria for identification of these cells in unanesthetized, unrestrained animals. We found that Hcrt cells have broad action potentials with elongated later positive deflections that distinguish them from adjacent antidromically identified cells. They are relatively inactive in quiet waking but are transiently activated during sensory stimulation. Hcrt cells are silent in slow wave sleep and tonic periods of REM sleep, with occasional burst discharge in phasic REM. Hcrt cells discharge in active waking and have moderate and approximately equal levels of activity during grooming and eating and maximal activity during exploratory behavior. Our findings suggest that these cells are activated during emotional and sensorimotor conditions similar to those that trigger cataplexy in narcoleptic animals. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst Sepul, North Hills, CA 91343 USA. RP Mileykovskiy, BY (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. EM bmileyko@ucla.edu; jsiegel@ucla.edu FU NIMH NIH HHS [MH064109, MH071350]; NINDS NIH HHS [NS14610] NR 83 TC 424 Z9 436 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 2 PY 2005 VL 46 IS 5 BP 787 EP 798 DI 10.1016/j.neuron.2005.04.035 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 934EN UT WOS:000229689800012 PM 15924864 ER PT J AU Oxman, MN Levin, MJ Johnson, GR Schmader, KE Straus, SE Gelb, LD Arbeit, RD Simberkoff, MS Gershon, AA Davis, LE Weinberg, A Boardman, KD Williams, HM Zhang, JHY Peduzzi, PN Beisel, CE Morrison, VA Guatelli, JC Brooks, PA Kauffman, CA Pachucki, CT Neuzil, KM Betts, RF Wright, PF Griffin, MR Brunell, P Soto, NE Marques, AR Keay, SK Goodman, RP Cotton, DJ Gnann, JW Loutit, J Holodniy, M Keitel, WA Crawford, GE Yeh, SS Lobo, Z Toney, JF Greenberg, RN Keller, PM Harbecke, R Hayward, AR Irwin, MR Kyriakides, TC Chan, CY Chan, ISF Wang, WWB Annunziato, PW Silber, JL AF Oxman, MN Levin, MJ Johnson, GR Schmader, KE Straus, SE Gelb, LD Arbeit, RD Simberkoff, MS Gershon, AA Davis, LE Weinberg, A Boardman, KD Williams, HM Zhang, JHY Peduzzi, PN Beisel, CE Morrison, VA Guatelli, JC Brooks, PA Kauffman, CA Pachucki, CT Neuzil, KM Betts, RF Wright, PF Griffin, MR Brunell, P Soto, NE Marques, AR Keay, SK Goodman, RP Cotton, DJ Gnann, JW Loutit, J Holodniy, M Keitel, WA Crawford, GE Yeh, SS Lobo, Z Toney, JF Greenberg, RN Keller, PM Harbecke, R Hayward, AR Irwin, MR Kyriakides, TC Chan, CY Chan, ISF Wang, WWB Annunziato, PW Silber, JL CA Shingles Prevention Study Grp TI A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INACTIVATED VARICELLA VACCINE; IMMUNE-RESPONSES; NATURAL-HISTORY; HEALTH SURVEY; VIRUS; PAIN; QUESTIONNAIRE; RECIPIENTS; SEVERITY; VALIDITY AB BACKGROUND The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster ( 315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia ( 27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent ( P< 0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent ( P< 0.001), and reduced the incidence of herpes zoster by 51.3 percent ( P< 0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults. C1 VA San Diego Healthcare Syst, Shingles Prevent Study, La Jolla, CA 92161 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. Durham VA Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. Duke Univ, Med Ctr, Ctr Aging, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. St Louis VA Med Ctr, St Louis, MO USA. Washington Univ, Dept Med, St Louis, MO USA. VA Boston Healthcare Syst, Boston, MA USA. VA New York Harbor Healthcare Syst, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Columbia Univ, New York, NY USA. New Mexico VA Healthcare Syst, Albuquerque, NM USA. VA Cooperat Studies Program Clin Res Pharm Coordi, Albuquerque, NM USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Vet Affairs Edward Hines Jr Hosp, Chicago, IL USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Baltimore VA Med Ctr, Baltimore, MD 21218 USA. Birmingham VA Med Ctr, Birmingham, AL USA. VA Palo Alto Healthcare Syst, Palo Alto, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Vet Adm Med Ctr, Northport, NY 11768 USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. Lexington VA Med Ctr, Lexington, KY 40511 USA. Merck Res Labs, W Point, PA USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Oxman, MN (reprint author), VA San Diego Healthcare Syst, Shingles Prevent Study, Mail Code 111F-1,3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM mnoxman@ucsd.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 NR 38 TC 997 Z9 1041 U1 2 U2 51 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 JUN 2 PY 2005 VL 352 IS 22 BP 2271 EP 2284 DI 10.1056/NEJMoa051016 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 930VY UT WOS:000229446400004 PM 15930418 ER PT J AU Nappi, J Okamura, A Frimmel, H Dachman, A Yoshida, H AF Nappi, J Okamura, A Frimmel, H Dachman, A Yoshida, H TI Region-based supine-prone correspondence for the reduction of false-positive CAD polyp candidates in CT colonography SO ACADEMIC RADIOLOGY LA English DT Article DE computer-aided detection (CAD); false-positive (FP) reduction; CT colonography (CTC); virtual colonoscopy ID COMPUTERIZED DETECTION; VIRTUAL COLONOSCOPY; VOLUMETRIC FEATURES; NEURAL NETWORKS; COLONIC POLYPS; PERFORMANCE; REGISTRATION; DIAGNOSIS; CANCER AB Rationale and Objectives. Radiologists often compare the supine and prone data sets of a patient to confirm potential polyp findings in computed tomographic (CT) colonography (CTC). We developed a new automated method that uses region-based supine-prone correspondence for the reduction of false-positive (FP) polyp candidates in computer-aided detection (CAD) for CTC. Materials and Methods. Up to six anatomic landmarks are established by use of the extracted region of the colonic lumen. A region-growing scheme with distance calculations is used to divide the colonic lumen into overlapping segments that match in the supine and prone data sets. Polyp candidates detected by means of a CAD scheme are eliminated in colonic segments that have sufficient diagnostic quality and contain polyp candidates in only one of the data sets of a patient. The method was evaluated with 121 CTC cases, including 42 polyps of 5 mm or greater in 28 patients, obtained by use of single- and multidetector CT scanners with standard precolonoscopy cleansing. Results. Complete or partial correspondence was established in 71% of cases. Based on a leave-one-patient-out evaluation, application of the method reduced 19% of FP results reported by our CAD scheme at a 90.5% by-polyp detection sensitivity, without loss of any true-positive results. The resulting CAD scheme yielded 2.4 FP results per patient, on average, with the use of the correspondence method, whereas it yielded 3.0 FP results per patient without the use of the method. Conclusion. The correspondence method is potentially useful for improving the specificity of CAD in CTC. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Zero Emerson Pl 3A, Boston, MA 02114 USA. EM jnappi@partners.org OI Nappi, Janne/0000-0002-0108-0992 FU NCI NIH HHS [CA095279] NR 28 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2005 VL 12 IS 6 BP 695 EP 707 DI 10.1016/j.acra.2004.12.026 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 934OC UT WOS:000229717100005 PM 15935968 ER PT J AU Buckley, TC Mozley, SL Holohan, DR Walsh, K Beckham, JC Kassel, JD AF Buckley, TC Mozley, SL Holohan, DR Walsh, K Beckham, JC Kassel, JD TI A psychometric evaluation of the Fagerstrom Test for Nicotine Dependence in PTSD smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE Fagerstrom; FTND; psychometric; smoking; posttraumatic stress disorder (PTSD) ID QUESTIONNAIRE AB Rates of smoking among individuals with psychiatric conditions are greater than rates seen in the general population, yet little is known about the psychometric properties of commonly used nicotine dependence instruments among psychiatric smokers. This study examined the reliability, validity, and factor structure of the Fagerstrom Test for Nicotine Dependence (FTND) among psychiatric smokers. Results revealed that the FTND had good test-retest reliability, convergent validity, and discriminant validity. A factor-analytic examination converged on a two-factor solution, reflecting two correlated but separate processes related to nicotine dependence. In total, the results revealed that the FTND performs as well-from a psychometric perspective-with psychiatric smokers, as it does with nonpsychiatric smokers. © 2004 Elsevier Ltd. All rights reserved. C1 Natl Ctr PTSD 116B2, VA Boston Healthcare Syst, Boston, MA 02131 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Virginia VA Med Ctr, Salem, VA USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Illinois, Chicago, IL USA. RP Buckley, TC (reprint author), Natl Ctr PTSD 116B2, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02131 USA. EM Todd.Buckley@med.va.gov FU NIDA NIH HHS [K24 DA016388, K01 DA016273-01, R03 DA15113-01] NR 6 TC 18 Z9 18 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUN PY 2005 VL 30 IS 5 BP 1029 EP 1033 DI 10.1016/j.addbeh.2004.09.005 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 931WE UT WOS:000229515400016 PM 15893100 ER PT J AU Farrow, MA Somasundaran, M Zhang, CS Gabuzda, D Sullivan, JL Greenough, TC AF Farrow, MA Somasundaran, M Zhang, CS Gabuzda, D Sullivan, JL Greenough, TC TI Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-ANTIGEN; SOR GENE; NONPROGRESSIVE INFECTION; ENHANCES RECOGNITION; ANTIVIRAL ACTIVITY; KARYOPHERIN ALPHA; CO-ENCAPSIDATION; ENZYME APOBEC3G; PROTEIN BINDS AB Recent reports have determined that HIV-1 Vif counteracts an innate antiviral cellular factor, Apobec3G. However, the function of Vif during HIV-1 pathogenesis remains poorly understood. To gain a better understanding of Vif function, the viral isolate from an HIV-1-infected long-term nonprogressor (LTNP) that displayed a Vif-mutant replication phenotype was studied. This LTNP has been infected since before 1983 and has no HIV-related disease in the absence of antiretroviral therapy. From separate samples, obtained on more than one study visit, virus grew in cocultures of LTNP cells with Vif-complementing T cell lines, but not the parental T cell lines. An unusual amino acid motif (KKRK) was found in the Vif sequence at positions 90 to 93. Since this motif commonly functions as a nuclear localization sequence, experiments were performed to determine the ability of this KKRK motif to mediate nuclear localization of Vif. Wild-type Vif displayed a predominantly cytoplasmic distribution. In contrast, the KKRK Vif showed a predominantly nuclear localization. The effect of the KKRK mutation on virus production and infectivity was also studied. The KKRK motif that mislocalizes Vif to the nucleus also reduces viral replication and infectivity in nonpermissive cells. Our data highlight the importance of Vif in HIV- 1 pathogenesis and also provide a unique tool to investigate the interaction of Vif and Apobec3G. C1 Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Greenough, TC (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Biotech 2 373 Plantat St,Suite 318, Worcester, MA 01605 USA. EM thomas.greenough@umassmed.edu FU NHLBI NIH HHS [HL42257]; NIAID NIH HHS [AI50490, AI28691, AI36186, AI39400, AI42845, AI62555] NR 58 TC 21 Z9 25 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2005 VL 21 IS 6 BP 565 EP 574 DI 10.1089/aid.2005.21.565 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 946CU UT WOS:000230550500007 PM 15989462 ER PT J AU Farrell, JJ Friedman, LS AF Farrell, JJ Friedman, LS TI Review article: the management of lower gastrointestinal bleeding SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID ARGON PLASMA COAGULATION; HEMORRHAGIC RADIATION PROCTITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SUPERSELECTIVE MICROCOIL EMBOLIZATION; SELECTIVE ARTERIAL EMBOLIZATION; RED-CELL SCINTIGRAPHY; YAG LASER TREATMENT; OF-THE-LITERATURE; COLONIC HEMORRHAGE; DIVERTICULAR HEMORRHAGE AB Several recent advances have been made in the evaluation and management of acute lower gastrointestinal bleeding. This review focuses on the management of lower gastrointestinal bleeding, especially acute severe bleeding. The aim of the study was to critically review the published literature on important management issues in lower gastrointestinal bleeding, including haemodynamic resuscitation, diagnostic evaluation, and endoscopic, radiologic, and surgical therapy, and to develop an algorithm for the management of lower gastrointestinal bleeding, based on this literature review. Publications pertaining to lower gastrointestinal bleeding were identified by searches of the MEDLINE database for the years 1966 to December 2004. Clinical trials and review articles were specifically identified, and their reference citation lists were searched for additional publications not identified in the database searches. Clinical trials and current clinical recommendations were assessed by using commonly applied criteria. Specific recommendations are made based on the evidence reviewed. Approximately, 200 original and review articles were reviewed and graded. There is a paucity of high-quality evidence to guide the management of lower gastrointestinal bleeding, and current endoscopic, radiologic, and surgical practices appear to reflect local expertise and availability of services. Endoscopic literature supports the role of urgent colonoscopy and therapy where possible. Radiology literature supports the role of angiography, especially after a positive bleeding scan has been obtained. Limited surgical data support the role of segmental resection in the management of persistent lower gastrointestinal bleeding after localization by either colonoscopy or angiography. There is limited high-quality research in the area of lower gastrointestinal bleeding. Recent advances have improved the endoscopic, radiologic and surgical management of this problem. However, treatment decisions are still often based on local expertise and preference. With increased access to urgent therapeutic endoscopy for the management of acute upper gastrointestinal bleeding, diagnostic and therapeutic colonoscopy can be expected to play an increasing role in the management of acute lower gastrointestinal bleeding. C1 Univ Calif Los Angeles, Hlth Sci Ctr, UCLS Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Boston, MA USA. Newton Wellesley Hosp, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Farrell, JJ (reprint author), Univ Calif Los Angeles, Hlth Sci Ctr, UCLS Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. EM jfarrell@mednet.ucla.edu NR 199 TC 58 Z9 64 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN 1 PY 2005 VL 21 IS 11 BP 1281 EP 1298 DI 10.1111/j.1365-2036.2005.02485.x PG 18 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 930AW UT WOS:000229389200001 PM 15932359 ER PT J AU Khachemoune, A Welsh, R Ehrsam, E AF Khachemoune, A Welsh, R Ehrsam, E TI An ederly woman with a non-healing ulcer SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; MARJOLINS ULCER C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Khachemoune, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 40 Blossom St BAR 314, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUN 1 PY 2005 VL 71 IS 11 BP 2163 EP 2165 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 931XD UT WOS:000229517900018 PM 15952447 ER PT J AU Giugliano, RP Newby, LK Harrington, RA Gibson, CM Van de Werf, F Armstrong, P Montalescot, G Gilbert, J Strony, JT Califf, RM Braunwald, E AF Giugliano, RP Newby, LK Harrington, RA Gibson, CM Van de Werf, F Armstrong, P Montalescot, G Gilbert, J Strony, JT Califf, RM Braunwald, E CA EARLY ACS Steering Comm TI The Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial: A randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded-eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome - Study design and rationale SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN; TROPONIN-I; CLOPIDOGREL; ASPIRIN; TIROFIBAN; RECEPTOR; THERAPY; INTERVENTIONS; PRETREATMENT AB Background The recent North American and European practice guidelines in patients with non-ST-segment elevation acute coronary syndrome (nSTE ACS) recommend glycoprotein IIb/IIIa (GpIIb-IIIa) inhibition in patients undergoing an early invasive treatment strategy. However, the guidelines are not explicit regarding the timing of initiation of GpIIb-IIIa antagonists, and there is marked variation in clinical practice regarding their use. Study Design The EARLY ACS trial will enroll 10500 patients in a prospective, randomized, double blind, international, multicenter investigation of early eptifibatide compared with placebo (with provisional eptifibatide in the catheterization laboratory) in patients with high-risk nSTE ACS in whom an invasive strategy is planned no sooner than the next calendar day. The primary efficacy end point is the 96-hour composite of all-cause mortality, nonfatal myocardial infarction, recurrent ischemia requiring urgent revascularization, or need for thrombotic bailout with GpIIb-IIIa inhibitor during percutaneous coronary intervention. The key secondary end point is the composite of death or nonfatal myocardial infarction within 30 days of enrollment. Implications The EARLY ACS trial will be the largest study to date to evaluate the utility of early GpIIb-IIIa inhibition in patients with nSTE ACS in whom an invasive approach is planned. This trial will provide important evidence regarding the benefit of initiating eptifibatide early after presentation with high-risk ACS versus delayed provisional use after coronary angiography. Furthermore, it will explore the ability of biomarkers to identify high-risk patients who may benefit from such an early aggressive approach. C1 TIMI Study Grp, Boston, MA 02115 USA. Duke Clin Res Inst, Durham, NC USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Alberta, Edmonton, AB, Canada. CHU Pitie Salpetriere, Paris, France. Millennium Pharmaceut, Cambridge, MA USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 28 TC 61 Z9 67 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2005 VL 149 IS 6 BP 994 EP 1002 DI 10.1016/j.ahj.2005.03.029 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947CZ UT WOS:000230622100012 PM 15976780 ER PT J AU Matthews, KA Sowers, MF Derby, CA Stein, E Miracle-McMahill, H Crawford, SL Pasternak, RC AF Matthews, KA Sowers, MF Derby, CA Stein, E Miracle-McMahill, H Crawford, SL Pasternak, RC TI Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN) SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; MEXICAN-AMERICANS; CHOLESTEROL; LIPOPROTEIN(A); PREDICTION; FIBRINOGEN; VARIABLES; PROGRAM AB Background We evaluated ethnic differences in the 10-year risk of myocardial infarction or coronary death derived from Framingham risk equation and in a composite measure of emerging cardiovascular disease risk factors in women and whether statistical adjustments for educational attainment, geographic location, and lifestyle attenuated the magnitude of the ethnic differences in risk. Methods Two thousand eight hundred thirty-four premenopausal women free of stroke, heart disease, or diabetes and aged of 42 to 52 years (1400 whites, 729 African American, 226 Hispanic, 231 Chinese, and 248 Japanese) had measurements of blood pressure, lipids and lipoproteins, waist circumference, glucose, insulin, lipoprotein(a), fibrinogen, factor VII, plasminogen activator inhibitor, tissue-type plasminogen activator antigen, and high-sensitivity C-reactive protein. Framingham risk score and number of risk factors in the top quartile of the distribution of risk factors not included in the Framingham score (called composite burden) were calculated. Results The unadjusted mean values for the two summary scores were higher among African Americans and Hispanics than other groups. Statistical adjustments for education and geographical site accounted for a majority of the ethnic differences, with an additional small effect of lifestyle for the composite burden score. Largest ethnic differences were apparent for waist circumference, lipoprotein(a), high-sensitivity C-reactive protein, and untreated blood pressure. Conclusions A substantial part of the risk associated with ethnicity can be attributed to socioeconomic status and geographical location. As the ethnic composition of the United States population becomes more diverse, it is important to appreciate the cardiovascular disease risk factor burden present in some minority groups. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Albert Einstein Coll Med, Dept Neurol & Epidemiol, Bronx, NY 10467 USA. Med Res Labs, Highland Hts, KY USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Matthews, KA (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM matthewska@upmc.edu RI Miracle, Maria /G-3482-2016 FU NIA NIH HHS [AG12546, AG12495, AG12505, AG12535, AG12553, AG12554, U01 AG12531]; NINR NIH HHS [U01 NR04061]; PHS HHS [A12539] NR 28 TC 79 Z9 83 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2005 VL 149 IS 6 BP 1066 EP 1073 DI 10.1016/j.ahj.2004.08.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947CZ UT WOS:000230622100030 PM 15976790 ER PT J AU Dzavik, V Sleeper, LA Picard, MH Sanborn, TA Lowe, AM Gin, K Saucedo, J Webb, JG Menon, V Slater, JN Hochman, JS AF Dzavik, V Sleeper, LA Picard, MH Sanborn, TA Lowe, AM Gin, K Saucedo, J Webb, JG Menon, V Slater, JN Hochman, JS CA SHOCK Investigators TI Outcome of patients aged >= 75 years in the SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) trial: Do elderly patients with acute myocardial infarction complicated by cardiogenic shock respond differently to emergent revascularization? SO AMERICAN HEART JOURNAL LA English DT Article ID ANGIOPLASTY; SURVIVAL; MANAGEMENT AB Background, In the SHOCK trial, the group of patients aged 75 years did not appear to derive the mortality benefit from early revascularization (ERV) versus initial medical stabilization (IMS) that was seen in patients aged <75 years. We sought to determine the reason for this finding by examining the baseline characteristics and outcomes of the 2 treatment groups by age. Methods Patients with cardiogenic shock (CS) secondary to left ventricular (LV) failure were randomized to ERV within 6 hours or to a period of IMS. We compared the characteristics by treatment group of patients aged >= 75 years and of their younger counterparts. Results of the 56 enrolled patients aged >= 75 years, those assigned to ERV had lower IV ejection fraction at baseline than IMS-assigned patients (27.5% +/- 12.7% vs 35.6% +/- 11.6%, P =.051). In the elderly ERV and IMS groups, 54.2% and 31.3%, respectively, were women (P =.105) and 62.5% and 40.6%, respectively, had an anterior infarction (P=.177). The 30-day mortality rate in the ERV group was 75.0% in patients aged >= 75 years and 41.4% in those aged <75 years. In the IMS group, 30-day mortality was 53.1% for those aged >= 75 years, similar to the 56.8% for patients aged <75 years. Conclusions Overall, the elderly randomized to ERV did not have better survival than elderly IMS patients. Despite the strong association of age and death post-CS, elderly patients assigned to IMS had a 30-day mortality rate similar to that of IMS patients aged <75 years, suggesting that this was a lower-risk group with more favorable baseline characteristics. The lack of apparent benefit from ERV in elderly patients in the SHOCK trial may thus be due to differences in important baseline characteristics, specifically LV function, and play of chance arising from the small sample size. Therefore, the SHOCK trial overall finding of a 12-month survival benefit for ERV should be viewed as applicable to all patients, including those >= 75 years of age, with acute myocardial infarction complicated by CS. C1 Univ Hlth Network, Intervent Cardiol Program, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Evanston Northwestern Healthcare, Evanston, IL USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Oklahoma Med Ctr, Oklahoma City, OK USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ N Carolina, Chapel Hill, NC USA. NYU, New York, NY USA. RP Dzavik, V (reprint author), Toronto Gen Hosp, Univ Hlth Network, Intervent Cardiol Program, 12-224A Eaton N,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM vlad.dzavik@uhn.on.ca FU NHLBI NIH HHS [R01 HL50020, R01 HL49970] NR 21 TC 42 Z9 46 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2005 VL 149 IS 6 BP 1128 EP 1134 DI 10.1016/j.ahj.2005.03.045 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947CZ UT WOS:000230622100043 PM 15976798 ER PT J AU Chinman, M Hannah, G Wandersman, A Ebener, P Hunter, SB Imm, P Sheldon, J AF Chinman, M Hannah, G Wandersman, A Ebener, P Hunter, SB Imm, P Sheldon, J TI Developing a community science research agenda for building community capacity for effective preventive interventions SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE capacity; technical assistance; prevention ID SUBSTANCE-ABUSE PREVENTION; TECHNICAL ASSISTANCE; ORGANIZATIONAL CAPACITY; HEALTH; EMPOWERMENT; PROGRAMS; DIFFUSION; ACCOUNTABILITY; IMPLEMENTATION; ENVIRONMENTS AB Research has shown that prevention programming can improve community health when implemented well. There are examples of successful prevention in local communities, however many continue to face significant challenges, demonstrating a gap between science and practice. Common strategies within the United States to address this gap are available ( e. g., trainings), but lack outcomes. Building community capacity to implement high quality prevention can help communities achieve positive health outcomes, thereby narrowing the gap. While there is ample research on the efficacy of evidence-based programs, there is little on how to improve community capacity to improve prevention quality. In order to narrow the gap, a new model of research - one based in Community Science - is suggested that improves the latest theoretical understanding of community capacity and evaluates technologies designed to enhance it. In this article, we describe this model and suggest a research agenda that can lead to improved outcomes at the local level. C1 RAND Corp, Santa Monica, CA 90407 USA. W Los Angeles VA Healthcare Ctr, Mental Illness Res Educ & Clin Ctr VISN22, Los Angeles, CA USA. Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. RP Chinman, M (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA. EM chinman@rand.org FU ODCDC CDC HHS [CCR921459] NR 78 TC 84 Z9 84 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD JUN PY 2005 VL 35 IS 3-4 BP 143 EP 157 DI 10.1007/s10464-005-3390-6 PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 922UC UT WOS:000228863200004 PM 15909791 ER PT J AU Kelley, A Lloyd-Jones, DM Colvin, A Matthews, KA Sutton-Tyrrell, K Sowers, MF Sternfeld, B Pasternak, RC Chae, CU AF Kelley, A Lloyd-Jones, DM Colvin, A Matthews, KA Sutton-Tyrrell, K Sowers, MF Sternfeld, B Pasternak, RC Chae, CU TI C-reactive protein levels vary by ethnicity in the study of women's health across the nation (SWAN). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S51 EP S51 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100203 ER PT J AU El-Serag, HB Graham, DY Satia, JA Rabeneck, L AF El-Serag, HB Graham, DY Satia, JA Rabeneck, L TI Obesity is an independent risk factor for GERD symptoms and erosive esophagitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; GASTRIC-ACID SECRETION; BODY-MASS; HELICOBACTER-PYLORI; MORBIDLY OBESE; MOTILITY DISORDERS; BARIATRIC SURGERY; POPULATION; ADENOCARCINOMA; ASSOCIATION AB INTRODUCTION: An association between obesity and GERD symptoms has been reported; however, study results have been inconsistent and it is not known whether an association persists after adjusting for other known GERD risk factors. METHODS: We carried out a cross-sectional study to determine the prevalence and risk factors of GERD in volunteers (VA employees). Participants completed a Gastroesophageal Reflux Questionnaire, the Block 98 Food Frequency Questionnaire, provided height and weight information, and were invited for upper endoscopy with biopsies. Associations of body mass index (BMI) with GERD symptoms and erosive esophagitis were examined separately in multiple logistic regression analyses adjusting for age, sex, race, GERD symptoms, dietary intake, education level, family history of GERD, H. pylori infection, and the presence and distribution of gastritis. RESULTS: Four hundred and fifty-three persons (mean age 44 yr, 70% women and 43% black) provided complete information on heartburn, regurgitation, and BMI (50% of 915 who received questionnaires). Of the 196 who underwent endoscopy, 44 (22%) had esophageal erosions and 118 (26%) reported at least weekly heartburn or regurgitation. A dose-response relationship between frequency of heartburn or regurgitation and higher BMI was observed. Compared to participants without weekly symptoms, a significantly larger proportion of the 118 with these symptoms were either overweight (BMI 25-30) (35%vs 32%) or obese (BMI > 30) (39%vs 26%), p for linear trend 0.004. Relative to those with no esophageal erosions, those with erosions were more likely to be overweight (39%vs 26%) or obese (41%vs 32%), p= 0.04. Obese participants were 2.5 times as likely as those with normal BMI (< 25) to have reflux symptoms or esophageal erosions. The association between BMI and GERD symptoms persisted in direction and magnitude after adjustment for potential confounders. CONCLUSIONS: Overweight and obesity are strong independent risk factor of GERD symptoms and esophageal erosions. The amount or composition of dietary intake does not appear to be a likely explanation for these findings. C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. Univ Toronto, Dept Med, Toronto, ON, Canada. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 43 TC 239 Z9 251 U1 1 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2005 VL 100 IS 6 BP 1243 EP 1250 DI 10.1111/j.1572-0241.2005.41703.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 930QU UT WOS:000229432000007 PM 15929752 ER PT J AU Streim, JE AF Streim, JE TI Nursing homes and research in geriatric psychiatry SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID DEPRESSION; PREVALENCE; RESIDENTS; PERSPECTIVE; DISORDERS C1 Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. RP Streim, JE (reprint author), Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, 3535 Market St,Room 3055, Philadelphia, PA 19104 USA. EM jstreim@mail.med.upenn.edu NR 18 TC 2 Z9 2 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2005 VL 13 IS 6 BP 437 EP 440 DI 10.1176/appi.ajgp.13.6.437 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 933AZ UT WOS:000229597600001 ER PT J AU Oslin, DW AF Oslin, DW TI Treatment of late-life depression complicated by alcohol dependence SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 01-04, 2003 CL HONOLULU, HI SP Amer Assoc Geriatr Psychiat ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MAJOR DEPRESSION; GENERAL-POPULATION; CLINICAL-TRIAL; GENDER DIFFERENCES; FOLLOW-UP; NALTREXONE; DRINKING; DISORDERS AB Objectives: Among elderly patients, mental and physical illness are often present along with alcohol dependence. The interaction between alcohol use and concurrent physical or mental disabilities is complex and complicates treatment planning. The aim of this study was to test the efficacy of naltrexone combined with sertraline for the treatment of older adults with major depression and alcohol dependence. Methods: The sample was 74 subjects, age 55 and older, who met criteria for a depressive disorder along with alcohol dependence. All subjects were randomly assigned to 12 weeks of naltrexone 50 mg/day or placebo. Also, all subjects received sertraline 100 mg/day and individual weekly psychosocial support. Treatment response for alcohol consumption and depression was measured during the 12 weeks of treatment. Results: At baseline, the average age of subjects was 63.4, and subjects were drinking an average of 10.7 drinks per drinking day. The overall results are encouraging; 42% of the subjects had a remission of their depression and had no drinking relapses during the trial. There was no evidence for an added benefit of naltrexone in combination with sertraline, but there was significant correlation between any alcohol relapse during the trial and poor response to depression treatment. Conclusion: Patients with concurrent mental disorders, such as major depression and alcohol dependence, are increasingly prevalent in clinical practice and have been demonstrated to show poorer treatment response and higher treatment costs. The results of this trial underscore the importance of addressing alcohol use in the context of treating late-life depression. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Study Addict, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu FU NIMH NIH HHS [5P30 MH 52129, K08 MH001599, K08 MH001599-05, 1K08 MH 01599-01] NR 55 TC 29 Z9 30 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2005 VL 13 IS 6 BP 491 EP 500 DI 10.1176/appi.ajgp.13.6.491 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 933AZ UT WOS:000229597600008 PM 15956269 ER PT J AU Chew, ML Mulsant, BH Pollock, BG AF Chew, ML Mulsant, BH Pollock, BG CA CPAD Study Grp TI Serum anticholinergic activity and cognition in patients with moderate-to-severe dementia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; SENILE DEMENTIA; OLDER-ADULTS; PERFORMANCE AB Objective: The authors investigated the association between serum anticholinergic activity (SAA) and cognitive performance in a group of patients with moderate-to-severe dementia. Methods: SAA and cognitive performance were assessed in 26 patients admitted to a geropsychiatric unit for the treatment of behavioral disturbances associated with dementia. SAA was measured by radioreceptor competitive binding assay. Cognition was tested with the Mini-Mental State Exam and the Severe Impairment Battery. Results: Higher SAA was associated with lower cognitive performance. Conclusion: This study extends to patients with moderate-to-severe dementia the finding that higher SAA is associated with lower cognitive performance. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Div Geriatr & Neuropsychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Mulsant, BH (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM mulsantbh@upmc.edu FU NCRR NIH HHS [RR 00056]; NIA NIH HHS [AG 05133]; NIMH NIH HHS [MH 52247, MH 01613, MH 59666, MH 01509, MH 30915, MH 65416] NR 10 TC 37 Z9 38 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2005 VL 13 IS 6 BP 535 EP 538 DI 10.1176/appi.ajgp.13.6.535 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 933AZ UT WOS:000229597600013 PM 15956274 ER PT J AU Ansani, NT Vogt, M Henderson, BAF McKaveney, TP Weber, RJ Smith, RB Burda, M Kwoh, CK Osial, TA Starz, T AF Ansani, NT Vogt, M Henderson, BAF McKaveney, TP Weber, RJ Smith, RB Burda, M Kwoh, CK Osial, TA Starz, T TI Quality of arthritis information on the Internet SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE arthritis; comprehension; computers; Internet; quality assurance; World Wide Web ID WORLD-WIDE-WEB; HEALTH INFORMATION; PATIENT EDUCATION; MEDICAL INFORMATION; MANAGEMENT; ONLINE; SEARCH; UPDATE; BEWARE; GUIDE AB Purpose. The quality and reliability of Internet-based arthritis information were studied. Methods. The search terms "arthritis," "osteoarthritis," and "rheumatoid arthritis" were entered into the AOL, MSN, Yahoo, Google, and Lycos search engines. The Web sites for the first 40 matches generated by each search engine were grouped by URL suffix and evaluated on the basis of four categories of criteria: disease and medication information content, Web-site navigability, required literacy level, and currentness of information. Ratings were assigned by using an assessment tool derived from published literature (maximum score of 15 points). Results. Of the 600 arthritis Web sites identified, only 69 were unique and included in the analysis. Fifty-seven percent were .com sites, 20% .org sites, 7% .gov sites, 6% .edu sites, and 10% other sites. Total scores for individual sites reviewed ranged from 3 to 14. Eighty percent of .gov sites, 75% of .edu sites, 29% of other sites, 36% of .com sites, and 21% of .org sites were within the top tertile of scores. No Web site met the criterion for being understandable to people with no more than a sixth-grade reading ability. .Gov sites scored significantly higher overall than .com sites, .org sites, and other sites. .Edu sites also scored relatively well. Conclusion. The quality of arthritis information on the Internet varied widely. Sites with URLs having suffixes of .gov and .edu were ranked higher than other types of sites. C1 Pfizer Inc, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Sch Pharm, Drug Informat Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Hlth Sci Lib Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15260 USA. RP Ansani, NT (reprint author), Pfizer Inc, 114 Alpine Circle, Pittsburgh, PA 15212 USA. EM nicole.ansani@pfizer.com NR 36 TC 38 Z9 41 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 1 PY 2005 VL 62 IS 11 BP 1184 EP 1189 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 931WV UT WOS:000229517100014 PM 15984050 ER PT J AU Duggirala, MK Cuddihy, RM Cuddihy, MT Naessens, JM Cha, SS Mandrekar, JN Leibson, CL AF Duggirala, MK Cuddihy, RM Cuddihy, MT Naessens, JM Cha, SS Mandrekar, JN Leibson, CL TI Predictors of blood pressure control in patients with diabetes and hypertension seen in primary care clinics SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; IMPROVES INSULIN SENSITIVITY; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR-DISEASE; UNITED-STATES; ROSIGLITAZONE; TRENDS; RISK AB Background: Blood pressure (BP) is not well controlled in the majority of patients with both diabetes and hypertension. This study was designed to identify predictors of BP control in patients with both diabetes and hypertension who are seen in primary care clinics. Methods: This retrospective study was conducted by identifying a cohort of patients diagnosed with diabetes before January 1, 2000 (inception) who met predefined criteria for hypertension at inception and who received primary care in the ensuing 3-year study period (January 1, 2000, to February 31, 2002). Using the mean of all BP values between January 1, 2002, and December 31, 2002, subjects were divided into two groups: those with controlled BP and those with uncontrolled BP. The distribution of clinical predictors was compared between the two groups. Independent predictors were identified using multivariate logistic regression. Results: Predictors of poor BP control were as follows: 1) isolated systolic hypertension at inception (OR = 0.62, CI = 0.47 to 0.82); 2) uncontrolled BP at inception (OR = 0.71, CI = 0.55 to 0.93); 3) use of oral hypoglycemic drugs versus diet and exercise alone or insulin use (OR = 0.73, CI = 0.56 to 0.95); 4) use of three or more antihypertensive drugs (OR = 0.74, CI = 0.56 to 0.97); and 5) older age (OR = 0.98, CI = 0.97 to 0.99). Predictors of better control were 1) use of nitrates (OR = 1.82, CI = 1.26 to 2.64); 2) history of coronary heart disease (OR = 1.47, CI = 1.08 to 2.00); and 3) at least one annual visit to subspecialist physician (OR = 1.43, CI = 1.09 to 1.88). Conclusions: Patients with both diabetes and hypertension who are older, have isolated systolic hypertension, use oral hypoglycemic drugs, or use three or more antihypertensive drugs should be targeted for better BP control. The roles of nitrate medication and subspecialist physicians in achieving better BP control needs further study. C1 Mayo Clin & Mayo Fdn, Mayo Clin Coll Med, Div Gen Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Clin Coll Med, Div Hlth Care Policy & Res, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Clin Coll Med, Div Biostat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Clin Coll Med, Div Epidemiol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Div Endocrinol, Diabet Unit, Newton, MA USA. Newton Wellesley Hosp, Newton, MA USA. Beth Israel Deaconess Med Ctr, Div Gen Internal Med & Primary Care, Boston, MA 02215 USA. RP Duggirala, MK (reprint author), Mayo Clin & Mayo Fdn, Mayo Clin Coll Med, Div Gen Internal Med, 200 1st St SW, Rochester, MN 55905 USA. EM duggirala.murali@mayo.edu NR 25 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2005 VL 18 IS 6 BP 833 EP 838 DI 10.1016/j.amjhyper.2004.12.016 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 934LO UT WOS:000229710500018 PM 15925744 ER PT J AU Mukherjee, S Rodrigues, E Aeschliman, DB Houk, RS Palmer, LJ Woodin, MA Weker, R Christiani, DC AF Mukherjee, S Rodrigues, E Aeschliman, DB Houk, RS Palmer, LJ Woodin, MA Weker, R Christiani, DC TI Urinary metal and polycyclic aromatic hydrocarbon biomarkers in boilermakers exposed to metal fume and residual oil fly ash SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE particulates; occupational health; biomarkers; carcinogens ID OCCUPATIONAL EXPOSURE; EPITHELIAL-CELLS; LUNG INJURY; ORGANIC-SUBSTANCES; DNA-DAMAGE; WORKERS; 1-HYDROXYPYRENE; VANADIUM; MANGANESE; COPPER AB Background Boilermakers are occupationally exposed to known carcinogens. Methods The association of urinary 1-hydroxy-pyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure, with biomarkers of metal exposure (vanadium, chromium, manganese, nickel, copper, and lead) in boilermakers exposed to metal fume from welding and dust particulates from residual oil fly ash (ROFA) was examined. A repeated measures cohort study was conducted during the overhaul of an oilfired boiler Twice-daily urine samples were obtained for 5 days and analyzed for cotinine, 1-OHP, and metals. Generalized estimating equations (GEE) were used to model the multivariate relationship of 1-OHP to the explanatory variables. Results Metal and 1-OHP levels were determined for 165 urine samples from 20 boilermakers and these levels increased during the workweek. However the 1-OHP level was not significantly associated with any individual metal level at any time point. Conclusion This suggests that boilermakers were occupationally exposed to PAH and metals, but 1-OHP as a PAH biomarker was unable to serve as a surrogate marker of metal exposure for the metals measured in this study. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Sir Charles Gairdner Hosp, Dept Pulm Physiol, WA Sleep Disorders Res Inst, Nedlands, WA 6009, Australia. Iowa State Univ, Dept Chem, Ames Lab, US Dept Energy, Ames, IA USA. Univ Western Australia, Ctr Med Res, QE II Med Ctr, Nedlands, WA 6009, Australia. Univ Western Australia, Western Australian Inst Med Res, QE II Med Ctr, Nedlands, WA 6009, Australia. Tufts Univ, Dept Civil & Environm Engn, Environm Hlth Program, Medford, MA 02155 USA. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Palmer, Lyle/K-3196-2014 OI Palmer, Lyle/0000-0002-1628-3055 FU NIEHS NIH HHS [ES00002, ES09860] NR 53 TC 8 Z9 8 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 2005 VL 47 IS 6 BP 484 EP 493 DI 10.1002/aijm.20161 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 931BE UT WOS:000229460000003 PM 15898092 ER PT J AU Sheffer, PJ Stout, JE Wagener, MM Muder, RR AF Sheffer, PJ Stout, JE Wagener, MM Muder, RR TI Efficacy of new point-of-use water filter for preventing exposure to Legionella and waterborne bacteria SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID RESISTANT PSEUDOMONAS-AERUGINOSA; COPPER-SILVER IONIZATION; LEGIONNAIRES-DISEASE; NOSOCOMIAL INFECTIONS; TAP WATER; SYSTEMS; TRANSMISSION; CULTURE; UNIT AB Background: Legionella species cause health care-acquired infections in which immunocompromised patients are disproportionately affected. Epidemiologic studies have demonstrated that point-of-use water fixtures are the reservoirs for these infections. The current approach to prevention is system-wide chemical disinfection of the hospital water system. These methods affect both low-risk and high-risk areas. A more effective approach to prevention may be a targeted approach aimed at protecting high-risk patients. One option is the application of a physical barrier (filter) at the point-of-use water fixture. Objectives: To evaluate the ability of point-of-use filters to eliminate Legionella and other pathogens from water. Methods: One hundred twenty-milliliter hot water samples were collected from 7 faucets (4 with filters and 3 without) immediately and after a 1-minute flush. Samples were collected every 2 or 3 days for 1 week. This cycle was repeated for 12 weeks. Samples were cultured for Legionella total heterotrophic plate count (HPC) bacteria, and Mycobacterium species. Results: Five hundred ninety-four samples were collected over 12 cycles. No Legionella or Mycobacterium were isolated from the faucets with filters between T = 0 and T = 8 days. The mean concentration of L pneumophila and Mycobacterium from the control faucets was 104.5 CFU/mL and 0.44 CFU/mL, respectively. The filters achieved a greater than 99% reduction in HPC bacteria in the immediate and postflush samples. Conclusions: Point-of-use filters completely eliminated L pneumophila and Mycobacterium from hot water samples. These Filter units could prevent exposure of high-risk patients to waterborne pathogens. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Stout, JE (reprint author), Vet Adm Med Ctr, Special Pathogens Lab, Univ Dr C, Pittsburgh, PA 15240 USA. EM Janet.Stout2@med.va.gov NR 23 TC 34 Z9 37 U1 2 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JUN PY 2005 VL 33 IS 5 SU 1 BP S20 EP S25 DI 10.1016/j.ajic.2005.03.012 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 937QJ UT WOS:000229940300002 PM 15940113 ER PT J AU Kraut, JA Kurtz, I AF Kraut, JA Kurtz, I TI Metabolic acidosis of CKD: Diagnosis, clinical characteristics, and treatment SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE metabolic acidosis; chronic kidney disease (CKD); renal failure; glomerular filtration rate (GFR) ID CHRONIC-RENAL-FAILURE; CHRONIC KIDNEY-DISEASE; SODIUM-BICARBONATE TREATMENT; NUTRITION EXAMINATION SURVEY; SERUM ELECTROLYTE PATTERNS; 3RD NATIONAL-HEALTH; HEMODIALYSIS-PATIENTS; AMMONIUM-CHLORIDE; TUBULAR-ACIDOSIS; BONE-DISEASE AB Metabolic acidosis is noted in the majority of patients with chronic kidney disease (CKD) when glomerular filtration rate (GFR) decreases to less than 20% to 25% of normal, although as many as 20% of individuals can have acid-base parameters close to or within the normal range. Acidosis generally is mild to moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22 mEq/L (mmol/L), and it is rare to see values less than 12 mEq/L (mmol/L) in the absence of an increased acid load. Degree of acidosis approximately correlates with severity of renal failure and usually is more severe at a lower GFR. The metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4 to 5 CKD. Several adverse consequences have been associated with metabolic acidosis, including muscle wasting, bone disease, impaired growth, abnormalities in growth hormone and thyroid hormone secretion, impaired insulin sensitivity, progression of renal failure, and exacerbation of O-2-microglobulin accumulation. Administration of base aimed at normalization of plasma bicarbonate concentration might be associated with certain complications, such as volume overload, exacerbation of hypertension, and facilitation of vascular calcifications. Whether normalization of plasma bicarbonate concentrations in all patients is desirable therefore requires additional study. In the present review, we describe clinical and laboratory characteristics of metabolic acidosis, discuss potential adverse effects, and address benefits and complications of therapy. (c) 2005 by the National Kidney Foundation, Inc. C1 VA Greater Los Angeles Hlth Care Syst, Nephrol Sect, Med & Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Div Nephrol, Los Angeles, CA 90073 USA. David Geffen Sch Med, Div Nephrol, Los Angeles, CA USA. RP Kraut, JA (reprint author), VA Greater Los Angeles Hlth Care Syst, Nephrol Sect, Med & Res Serv, 691-111L,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu NR 132 TC 111 Z9 114 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2005 VL 45 IS 6 BP 978 EP 993 DI 10.1053/j.ajkd.2005.03.003 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 936LH UT WOS:000229857000003 PM 15957126 ER PT J AU Subramanya, A Houghton, D Watnick, S AF Subramanya, A Houghton, D Watnick, S TI Steroid-responsive idiopathic glomerular capillary endotheliosis: Case report and literature review SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE glomerular capillary endotheliosis; glomerulonephritis; proteinuria; kidney diseases ID GROWTH-FACTOR RECEPTOR; RENAL INVOLVEMENT; THROMBOTIC MICROANGIOPATHIES; ANTIPHOSPHOLIPID ANTIBODIES; FACTOR-H; PREECLAMPSIA; PREGNANCY; LESION; NEPHROPATHY; DISEASE AB Glomerular capillary endotheliosis is a lesion of endothelial cell injury. Morphological characteristics are endothelial swelling with glomerular hypertrophy and a reduction in capillary lumen size. This lesion commonly is found in patients with thrombotic microangiopathy, but similar histopathologic characteristics have been reported in patients with other diseases. A previously healthy 39-year-old woman presented with progressive lower-extremity swelling and arthralgias for 1 week. She had no other symptoms and denied prior illness. Her examination was remarkable for hypertension and pitting edema. Urine showed dysmorphic red blood cells and proteinurla. Serum creatinine level increased from 1.1 to 2.0 mg/dL (97 to 177 mu mol/L) during several weeks. She did not meet criteria for systemic lupus erythematosus. Other test results included a negative pregnancy test and normal complement levels. Additional workup was negative for other causes of glomerular capillary endothellosis. She underwent 2 renal biopsies. The first showed marked endothelial cell swelling, and the second biopsy 2 months later showed disease progression. Both were consistent with glomerular capillary endotheliosis. Proteinuria and serum creatinine level elevation responded to methylprednisolone therapy within 1 week, recurred after steroid doses were tapered, and responded again after restarting steroid therapy with monthly cyclophosphamide infusions. The differential diagnosis for glomerular capillary endotheliosis is limited. Various causes have been implicated, such as dysregulation of vascular endothelial growth factor, abnormal collagen production, and endothelial abnormalities. We did not identify prior cases of idiopathic glomerular capillary endotheliosis in the literature. Idiopathic glomerular capillary endotheliosis may be a newly recognized entity potentially responsive to steroid and cytotoxic regimens. (c) 2005 by the National Kidney Foundation, Inc. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Dept Pathol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. RP Watnick, S (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Dept Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 26 TC 7 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2005 VL 45 IS 6 BP 1090 EP 1095 DI 10.1053/j.ajkd.2005.03.010 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 936LH UT WOS:000229857000016 PM 15957139 ER EF