FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Medarova, Z Tsai, S Evgenov, N Santamaria, P Moore, A AF Medarova, Zdravka Tsai, Sue Evgenov, Natalia Santamaria, Pere Moore, Anna TI In vivo imaging of a diabetogenic CD8+T cell response during type 1 diabetes progression SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; type 1 diabetes; antigen-specific immunity; IGRP; magnetic nanoparticles (MN); nonobese diabetic (NOD) mice ID CD8(+) T-CELLS; AVIDITY MATURATION; MICE; PANCREAS; RECEPTOR; IDENTIFICATION; AUTOIMMUNITY; LYMPHOCYTES; POPULATION; MELLITUS AB Type 1 diabetes is preceded by a long, protracted period of pancreatic islet inflammation by autoreactive lymphocytes. Noninvasive imaging of islet inflammation prior to the onset of hyperglycemia might have diagnostic and therapeutic implications, but this is not currently possible. Here, MRI is used to track, noninvasively, the accumulation diabetogenic CD8+ T-cells during type 1 diabetes progression in nonobese diabetic (NOD) mice. The contrast agent is an MRI probe (MN-NRP-V7) that specifically labels CD8+ T-cells recognizing residues 206-214 of islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP(206-214)) in the context of the major histocompatibility complex (MHC) class I molecule H-2K(d). This probe consists of superparamagnetic iron oxide nanoparticles (MN) coated with K-d molecules presenting NRP-V7, a high-avidity mimotope of IGRP(206-214). NOD mice of different ages (5, 8, 15, and 24 weeks) were imaged by MRI before and after a single intravenous injection of MN-NRP-V7 or unmodified MN nanoparticles. MN-NRP-V7 accumulation, as determined by semi-quantitative MRI analysis of pancreas-associated T-2 relaxation time, was antigen -specific, age-dependent, and well correlated with the numbers of MN-NRP-V7-labeled CD8+ T-cells recovered from the pancreata of the treated mice. Antigen/MHC-coupled nanoparticles represent a promising new avenue for noninvasive imaging of lymphocyte inflammation in organ-specific autoimmunity and transplantation. C1 [Medarova, Zdravka; Evgenov, Natalia; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT,Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tsai, Sue; Santamaria, Pere] Univ Calgary, Fac Med, Inst Infect Immun & Inflammat,JMDRC, Dept Microbiol & Infect Dis, Calgary, AB, Canada. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT,Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK064850] NR 26 TC 25 Z9 26 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2008 VL 59 IS 4 BP 712 EP 720 DI 10.1002/mrm.21494 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 283OI UT WOS:000254645500006 PM 18302224 ER PT J AU Winter, JO Gokhale, M Jensen, RJ Cogan, SF Rizzo, JF AF Winter, Jessica O. Gokhale, Mrudula Jensen, Ralph J. Cogan, Stuart F. Rizzo, Joseph F., III TI Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings SO MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS LA English DT Article; Proceedings Paper CT Symposium on Advanced Processing of Biomaterials CY OCT 15-19, 2006 CL Cincinnati, OH SP Amer Ceram Soc, Assoc Iron & Steel Technol, ASM Int, Minerals, Met & Mat Soc DE tissue engineering; neural prosthesis; retina; BDNF ID IRIDIUM OXIDE AIROF; NEURITE OUTGROWTH; IN-VITRO; ELECTRICAL-STIMULATION; NEURAL STIMULATION; CHARGE-INJECTION; DRUG-DELIVERY; GROWTH-FACTOR; REGENERATION; CELLS AB Several groups are developing visual prostheses to aid patients with vision loss. While these devices have shown some success in the clinic, they are severely limited by poor resolution, and in many cases have as few as 15 electrodes. Pixel density is poor because high stimulation thresholds require large electrodes to minimize charge density that would otherwise damage the electrode and tissue. A significant contributor to high stimulation threshold requirements is poor biocompatibility. We investigated the application of one system popular in tissue engineering, drug-releasing hydrogels, as a mechanism to improve the tissue-electrode interface. Hydrogels studied (i.e., PEGPLA photocrosslinkable polymers) released neurotrophic factors (i.e., BDNF) known to promote neuron survival and neurite extension in the retina. Hydrogels were examined in co-culture with retinal explants for 7 and 14 days, at which time neurite extension and neurite density were measured. Neurite extension was enhanced in samples exposed to BDNF-releasing hydrogels at 7 days; however, these increases were absent by day 14 suggesting declining drug release. Thus, PEGPLA hydrogels are excellent candidates for short-term (< 14 days) acute release of therapeutic factors in the retina, but will require additional modifications for application with neural prostheses. Additionally, these results suggest that the effects of neurotrophic factors are short-lived in the absence of additional support cues, and tissue engineering systems employing such factors may only produce transient benefits to the patient. (c) 2007 Elsevier B.V. All rights reserved. C1 [Winter, Jessica O.; Jensen, Ralph J.; Rizzo, Joseph F., III] VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. [Winter, Jessica O.; Gokhale, Mrudula] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Winter, Jessica O.] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. [Cogan, Stuart F.] EIC Labs, Norwood, MA 02062 USA. [Rizzo, Joseph F., III] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Winter, JO (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. EM winter.63@osu.edu OI Winter, Jessica/0000-0002-5370-0137 FU NINDS NIH HHS [R43 NS049687, R43 NS049687-01] NR 33 TC 17 Z9 17 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-4931 J9 MAT SCI ENG C-BIO S JI Mater. Sci. Eng. C-Biomimetic Supramol. Syst. PD APR 1 PY 2008 VL 28 IS 3 BP 448 EP 453 DI 10.1016/j.msec.2007.04.011 PG 6 WC Materials Science, Multidisciplinary SC Materials Science GA 295BX UT WOS:000255451100022 PM 21461345 ER PT J AU Kartha, A Brower, V Saitz, R Samet, JH Keane, TM Liebschutz, J AF Kartha, Anand Brower, Victoria Saitz, Richard Samet, Jeffrey H. Keane, Terence M. Liebschutz, Jane TI The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE PTSD; trauma; primary care; hospitalization; utilization ID MEDICAL UTILIZATION; PREVALENCE; IMPAIRMENT; VALIDATION; SYMPTOMS; UTILITY; PTSD AB Background: Trauma exposure and post-traumatic stress disorder (PTSD) increase healthcare utilization in veterans, but their impact on utilization in other populations is uncertain. Objectives: To examine the association of trauma exposure and PTSD with healthcare utilization, in civilian primary care patients. Research Design: Cross-sectional study. Subjects: English speaking patients at an academic, urban primary care clinic. Measures: Trauma exposure and current PTSD diagnoses were obtained from the Composite International Diagnostic Interview. Outcomes were nonmental health outpatient and emergency department visits, hospitalizations, and mental health outpatient visits in the prior year from an electronic medical record. Analyses included bivariate unadjusted and multivariable Poisson regressions adjusted for age, gender, income, substance dependence, depression, and comorbidities. Results: Among 592 subjects, 80% had >= 1 trauma exposure and 22% had current PTSD. In adjusted regressions, subjects with trauma exposure had more mental health visits [incidence rate ratio (IRR), 3.9; 95% confidence interval (CI), 1.1-14.1] but no other increased utilization. After adjusting for PTSD, this effect of trauma exposure was attenuated (IRR, 3.2; 95% CI, 0.9-11.7). Subjects with PTSD had more hospitalizations (IRR, 2.2; 95% CI, 1.4-3.7), more hospital nights (IRR, 2.6; 95% CI, 1.4-5.0), and more mental health visits (IRR, 2.2; 95% CI, 1.1-4.1) but no increase in outpatient and emergency department visits. Conclusions: PTSD is associated with more hospitalizations, longer hospitalizations, and greater mental healthcare utilization in urban primary care patients. Although trauma exposure is independently associated with greater mental healthcare utilization, PTSD mediates a portion of this association. C1 [Kartha, Anand; Saitz, Richard; Samet, Jeffrey H.; Liebschutz, Jane] Boston Univ, Med Ctr, CARE Unit, Gen Internal Med Sect, Boston, MA USA. [Kartha, Anand; Saitz, Richard; Samet, Jeffrey H.; Liebschutz, Jane] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kartha, Anand; Keane, Terence M.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Brower, Victoria] Massachusetts Behav Hlth Partnership, Boston, MA USA. [Saitz, Richard] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Saitz, Richard] Boston Univ, Youth Alcohol Prevent Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. [Samet, Jeffrey H.; Liebschutz, Jane] Boston Univ, Sch Med, Dept Social & Behav Sci, Boston, MA 02118 USA. [Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Keane, Terence M.] Natl Ctr Post Traumat Stress Disorder, Boston, MA USA. RP Kartha, A (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy,Mail Stop 111, W Roxbury, MA 02132 USA. EM anand.kartha@med.va.gov FU NIDA NIH HHS [K23 DA016665, K23 DA01665, K23 DA016665-04] NR 29 TC 25 Z9 25 U1 1 U2 6 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 APR PY 2008 VL 46 IS 4 BP 388 EP 393 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 282ME UT WOS:000254571100008 PM 18362818 ER PT J AU Reiser, I Nishikawa, RM Edwards, AV Kopans, DB Schmidt, RA Papaioannou, J Moore, RH AF Reiser, I. Nishikawa, R. M. Edwards, A. V. Kopans, D. B. Schmidt, R. A. Papaioannou, J. Moore, R. H. TI Automated detection of microcalcification clusters for digital breast tomosynthesis using projection data only: A preliminary study SO MEDICAL PHYSICS LA English DT Article DE breast imaging; tomosynthesis; computer-aided detection; microcalcification cluster ID FLAT-PANEL DETECTOR; COMPUTER-AIDED DIAGNOSIS; PHYSICAL-CHARACTERISTICS; SCREENING MAMMOGRAPHY; SYSTEM; IMAGES; PERFORMANCE; PROTOTYPE; NOISE AB Digital breast tomosynthesis (DBT) is a promising modality for breast imaging in which an anisotropic volume image of the breast is obtained. We present an algorithm for computerized detection of microcalcification clusters (MCCs) for DBT. This algorithm operates on the projection views only. Therefore it does not depend on reconstruction, and is computationally efficient. The algorithm was developed using a database of 30 image sets with microcalcifications, and a control group of 30 image sets without visible findings. The patient data were acquired on the first DBT prototype at Massachusetts General Hospital. Algorithm sensitivity was estimated to be 0.86 at 1.3 false positive clusters, which is below that of current MCC detection algorithms for full-field digital mammography. Because of the small number of patient cases, algorithm parameters were not optimized and one linear classifier was used. An actual limitation of our approach may be that the signal-to-noise ratio in the projection images is too low for microcalcification detection. Furthermore, the database consisted of predominantly small MCC. This may be related to the image quality obtained with this first prototype. (c) 2008 American Association of Physicists in Medicine. C1 [Reiser, I.; Nishikawa, R. M.; Edwards, A. V.; Schmidt, R. A.; Papaioannou, J.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Kopans, D. B.; Moore, R. H.] Massachusetts Gen Hosp, Boston, MA 02214 USA. RP Reiser, I (reprint author), Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. EM ireiser@uchicago.edu OI Nishikawa, Robert/0000-0001-7720-9951 FU NCI NIH HHS [R33 CA109963] NR 36 TC 34 Z9 37 U1 0 U2 3 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 APR PY 2008 VL 35 IS 4 BP 1486 EP 1493 DI 10.1118/1.2885366 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 281PN UT WOS:000254510700037 PM 18491543 ER PT J AU Park, MA Mahmood, A Zimmerman, RE Limpa-Amara, N Makrigiorgos, GM Moore, SC AF Park, Mi-Ae Mahmood, Ashfaq Zimmerman, Robert E. Limpa-Amara, Naengnoi Makrigiorgos, G. Mike Moore, Stephen C. TI Adsorption of metallic radionuclides on plastic phantom walls SO MEDICAL PHYSICS LA English DT Article DE radioactivity distribution; internal dosimetry; plastic phantom ID DOSIMETRY; THERAPY; RECONSTRUCTION AB Metal radionuclide solutions at neutral pH adhere to plastic containers. Adsorption of radionuclides on the walls of phantoms leads to a nonuniform activity distribution, which could adversely affect imaging studies, as well as phantom-based validations of absorbed dose calculations used in radioimmunotherapy, requiring accurate knowledge of the underlying activity distribution. In the work reported here, the authors determined the degree of metal chelation required to minimize metallic radionuclide oxide formation and adsorption on phantom walls in order to yield more reliable experimental data for validating image-based dosimetry. Using hollow spherical plastic phantoms, the authors evaluated three different radionuclides, I-131, In-111, and Y-90, in solutions containing three different concentrations of the chelator, ethylenediaminetetraacetate (EDTA). Adsorption to plastic walls was determined using mu SPECT imaging and/or by counting aliquots of solutions. Reconstructed images and measurements of I-131 activity showed that it was uniformly distributed within all spheres; however, images of In-111 in 0.25-mu M EDTA indicated that the activity concentration near the wall was much higher than that in the middle of the sphere. The decrease in activity concentration near the center of the spheres was similar to 47%. Y-90 in 0.25-mu M EDTA behaved similarly; the activity concentration of Y-90 decreased by 46%. For an In-111 or Y-90 radioactivity concentration of 0.74 MBq/mL, a 2.5-mu M EDTA solution was required to achieve a uniform distribution, suggesting that, under our experimental conditions, similar to 700 EDTA molecules were required for each radiometal atom to prevent precipitation and adsorption on poly(methylmethacrylate). For certain radiometals, e.g., In-111 or Y-90, adequate chelation is essential to achieve uniform activity concentration values and homogeneous distribution within the phantom compartments. (c) 2008 American Association of Physicists in Medicine. C1 [Park, Mi-Ae; Moore, Stephen C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Moore, Stephen C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Makrigiorgos, G. Mike] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Park, MA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA119334, R01-CA119334]; NCRR NIH HHS [S10-RR017224]; NIBIB NIH HHS [R01 EB001989, R01 EB001989-11A1, R01-EB001989] NR 15 TC 5 Z9 5 U1 0 U2 3 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 APR PY 2008 VL 35 IS 4 BP 1606 EP 1610 DI 10.1118/1.2871191 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 281PN UT WOS:000254510700048 PM 18491554 ER PT J AU Sajid-Crockett, S Singer, FR Hershman, JM AF Sajid-Crockett, Saima Singer, Frederick R. Hershman, Jerome M. TI Cinacalcet for the treatment of primary hyperparathyroidism SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CALCIUM-SENSING RECEPTOR; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; CALCIMIMETIC AGENTS; ORAL ALENDRONATE; SERUM-CALCIUM; PARATHYROIDECTOMY; HYDROCHLORIDE; OSTEOPOROSIS; MANAGEMENT AB Primary hyperparathyroidism (HPT) is the leading cause of hypercalcemia in the outpatient setting, and it is treated primarily by parathyroidectomy. There are few nonsurgical treatment options for patients who do not wish to have surgery, who have failed surgery, or who have contraindications to surgery. Cinacalcet increases the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing serum calcium levels. We conducted a retrospective chart review from 2004 to 2006 to investigate the efficacy of cinacalcet in reducing serum total calcium, ionized calcium, and parathyroid hormone (PTH) in patients with primary HPT. Patients were started on cinacalcet if they met at least one indication for parathyroidectomy, which includes T score less than -2.5 standard deviations from the mean, serum calcium 1 mg/dL above the upper limit of normal, 24-hour urine calcium above 400 mg/dL, age less than 50 years, or a creatinine clearance that is 30% below age- and sex-inatched controls. The primary outcome was normalization of serum calcium. A total of 18 patients with primary HPT were started on cinacalcet: 16 men and 2 women with a mean age of 70 years. Mean baseline serum calcium was 10.60 +/- .53 mg/dL; ionized serum calcium, 1.45 +/- .07 mmol/L; and serum PTH, 141 +/- 78 pg/mL. After treatment with cinacalcet, the mean serum calcium decreased to 9.46 +/- .34 mg/dL, ionized calcium decreased. to 1.26 +/- 1.06 mmol/L, and PTH decreased to 108 +/- 64.5 pg/mL. Ninety-four percent of the patients on cinacalcet had normal total serum calcium, 81% had normal serum ionized calcium, whereas only 25% had a normal serum PTH level. Cinacalcet normalizes serum calcium in most patients while only modestly reducing serum PTH levels. (c) 2008 Elsevier Inc. All rights reserved. C1 [Sajid-Crockett, Saima; Singer, Frederick R.; Hershman, Jerome M.] VA Greater Los Angeles Hltcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Sajid-Crockett, Saima; Singer, Frederick R.; Hershman, Jerome M.] John Wayne Canc Inst, Santa Monica, CA 90404 USA. RP Sajid-Crockett, S (reprint author), VA Greater Los Angeles Hltcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. EM ssajid@sierraendocrine.com NR 26 TC 20 Z9 21 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2008 VL 57 IS 4 BP 517 EP 521 DI 10.1016/j.metabol.2007.11.014 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275VJ UT WOS:000254099900013 PM 18328354 ER PT J AU Thomas, AV Berezovska, O Hyman, BT von Arnim, CAF AF Thomas, Anne V. Berezovska, Oksana Hyman, Bradley T. von Arnim, Christine A. F. TI Visualizing interaction of proteins relevant to Alzheimer's disease in intact cells SO METHODS LA English DT Article DE alzheimer's disease; amyloid precursor protein (APP); low density lipoprotein receptor-related protein (LRP); fluorescence resonance energy transfer (FRET); fluorescence lifetime imaging microscopy (FLIM) ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; LIFETIME IMAGING MICROSCOPY; RESONANCE ENERGY-TRANSFER; PRESENILIN-1; SECRETASE; LRP; APP; PHOSPHORYLATION; CONFORMATION AB To understand normal function of memory studying models of pathological memory decline is essential. The most common form of dementia leading to memory decline is Alzheimer's disease (AD), which is characterized by the presence of neurofibrillary tangles and amyloid plaques in the affected brain regions. Altered production of amyloid beta (A beta) through sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases seems to be a central event in the molecular pathogenesis of the disease. Thus, the study of the complex interplay of proteins that are involved in or modify A beta production is very important to gain insight into the pathogenesis of AD. Here, we describe the use of Fluorescence lifetime imaging microscopy (FLIM), a Fluorescence resonance energy transfer (FRET)-based method, to visualize protein-protein-interaction in intact cells, which has proven to be a valuable method in AD research. (c) 2007 Elsevier Inc. All rights reserved. C1 [von Arnim, Christine A. F.] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. [Thomas, Anne V.] Univ Cologne, Dept Neurol, D-5000 Cologne 41, Germany. [Berezovska, Oksana; Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Boston, MA 02114 USA. RP von Arnim, CAF (reprint author), Univ Ulm, Dept Neurol, Oberer Eselsberg 45, D-89081 Ulm, Germany. EM christine.arnim@uni-ulm.de FU NIA NIH HHS [P01 AG015379-060003, P01 AG015379, P01 AG015379-020003, P01 AG015379-040003, P01 AG015379-080003, P01AG015379, P50 AG005134, R37 AG012406-06, R37 AG012406-08, R37 AG012406-11, R37 AG012406-13, R37 AG012406, P01 AG015379-010003, P01 AG015379-030003, P01 AG015379-050003, P01 AG015379-070003, P01 AG015379-090003, P01 AG015379-100003, R37 AG012406-07, R37 AG012406-09, R37 AG012406-09S1, R37 AG012406-10, R37 AG012406-12, R37 AG012406-14, R37AG12406] NR 25 TC 11 Z9 11 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 1046-2023 J9 METHODS JI Methods PD APR PY 2008 VL 44 IS 4 BP 299 EP 303 DI 10.1016/j.ymeth.2007.02.003 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295CG UT WOS:000255452000003 PM 18374273 ER PT J AU Carlson, JM Brumme, ZL AF Carlson, Jonathan M. Brumme, Zabrina L. TI HIV evolution in response to HLA-restricted CTL selection pressures: a population-based perspective SO MICROBES AND INFECTION LA English DT Review DE human immunodeficiency virus; human leukocyte antigen; cytotoxic T lymphocytes; immune escape; viral evolution; vaccine ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; ESCAPE MUTATION; VACCINE DESIGN; INFECTION; AIDS; TRANSMISSION; PROGRESSION; DIVERSITY AB Cytotoxic T lymphocytes (CTL) recognize antigenic peptides displayed by HLA class I molecules on the infected cell surface and represent a major selective force driving HIV evolution through a phenomenon known as "immune escape". Here we summarize recent advances in our understanding of the consequences of CTL escape on HIV evolution at the population level and discuss its implications for HIV vaccine design. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Brumme, Zabrina L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA. [Carlson, Jonathan M.] Microsoft Res, Redmond, WA USA. [Carlson, Jonathan M.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. RP Brumme, ZL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM zbrumme@partners.org NR 42 TC 32 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2008 VL 10 IS 5 BP 455 EP 461 DI 10.1016/j.micinf.2008.01.013 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 316XI UT WOS:000256982600001 PM 18407775 ER PT J AU Tongchusak, S Leelayuwat, C Brusic, V Chaiyaroj, SC AF Tongchusak, Songsak Leelayuwat, Chanvit Brusic, Vladimir Chaiyaroj, Sansanee C. TI In silico prediction and immunological validation of common HLA-DRB1-restricted T cell epitopes of Candida albicans secretory aspartyl proteinase 2 SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE C. albicans; HLA-DRB1 restriction; secretory aspartyl proteinase; T cell epitope prediction ID MONOCLONAL-ANTIBODY; HLA-DR; IDENTIFICATION; PEPTIDES; VIRUS; RECOGNITION; PROTEINASE; EXPRESSION; HAPLOTYPES; DISCOVERY AB Sap2 is the most abundant virulence factor expressed during Candida infection, and the principal protein known to induce antibody response during Candida infection in humans. Its role in T-cell activation however, has not yet been determined. Sequence analysis revealed that Sap2 contains two variable regions: Var1 and Var2. Computational predictions by the Hotspot Hunter program identified that Var1 contains three candidate T-cell epitopes, whereas Var2 contains four. Thirty-nine overlapping peptides of Sap2 were then synthesized, and tested for their ability to induce proliferation of PBMC from 12 donors. Peptides P11, P17 and P31 exhibited significantly higher proliferative indices when compared with those of other peptides or controls. P17 and P31 are located in the areas of prediction, while P11 is not. There were other peptides outside the prediction areas that could stimulate PBMC proliferation at low levels. Nevertheless, the proliferative noise caused by such peptides was ruled out by IL-2 ELISpot analysis. Only P17 and P31 were shown to induce clonal proliferation of IFN-gamma producing lymphocytes, suggesting that these two peptides contain T cell epitopes. P11, which stimulated IL-2 producing clones, contains a known B-cell epitope. Interestingly, P17 and P31 elicited both Th1 and Th2 cell responses with significant numbers of IL-13 secreting clones in response to stimulation. Taken together, the computer-based T cell epitope prediction method could identify the immunogenic T cell epitopes of C. albicans Sap2 that promiscuously bind to the HLA-DRB1 supertype. C1 [Tongchusak, Songsak; Chaiyaroj, Sansanee C.] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. [Leelayuwat, Chanvit] Khon Kaen Univ, Fac Assoc MEd Sci, Ctr Res & Dev Med Diagnost Labs, Khon Kaen, Thailand. [Chaiyaroj, Sansanee C.] Chulabhorn Res Inst, Pharmacol Lab, Bangkok, Thailand. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Chaiyaroj, SC (reprint author), Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. EM scscy@mahidol.ac.th NR 40 TC 3 Z9 5 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PD APR PY 2008 VL 52 IS 4 BP 231 EP 242 DI 10.1111/j.1348-0421.2008.00032.x PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 291RA UT WOS:000255213300005 PM 18426398 ER PT J AU Sohn, L Harada, ND AF Sohn, Linda Harada, Nancy D. TI Effects of racial/ethnic discrimination on the health status of minority veterans SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RACIAL DISPARITIES; VIETNAM VETERANS; CARE-SYSTEM; US VETERANS; EDUCATION; AFFAIRS; LIFE; ASSOCIATION; COMMUNITY AB As the veteran population becomes ethnically diverse, it is important to understand complex interrelationships between racism and health. This study examined the association between perceptions of discrimination and self-reported mental and physical health for Asian/Pacific Islander, African American, and Hispanic veterans. The data for this study come from the 2001 Veteran Identity Program Survey, which measured utilization of outpatient care, discrimination, and health status across three minority veteran groups. Multivariate regression methods were used to model self-reported mental and physical health on perceptions of discrimination controlling for demographic and socioeconomic characteristics. Findings revealed that racial/ethnic discrimination during military service was significantly associated with lower physical, but not mental health. Satisfaction with health care provider's sensitivity toward racial/ethnic background was significantly associated with better mental health. Findings highlight the importance of developing policies that address racial/ethnic discrimination during military service while providing health care services for veterans. C1 [Sohn, Linda; Harada, Nancy D.] VA Greater Los Angeles Hlth Care Syst, Sepulveda, CA 91343 USA. RP Sohn, L (reprint author), VA Greater Los Angeles Hlth Care Syst, 16111 Plummer St,Mail Code 118B,NHCU Bldg 99, Sepulveda, CA 91343 USA. NR 38 TC 9 Z9 9 U1 3 U2 11 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD APR PY 2008 VL 173 IS 4 BP 331 EP 338 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 288CL UT WOS:000254963700004 PM 18472621 ER PT J AU Hezel, AF Gurumurthy, S Granot, Z Swisa, A Chu, GC Bailey, G Dor, Y Bardeesy, N DePinho, RA AF Hezel, Aram F. Gurumurthy, Sushma Granot, Zvi Swisa, Avital Chu, Gerry C. Bailey, Gerald Dor, Yuval Bardeesy, Nabeel DePinho, Ronald A. TI Pancreatic Lkb1 deletion leads to acinar polarity defects and cystic neoplasms SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; TO-DUCTAL METAPLASIA; CELL POLARITY; TGF-ALPHA; GLUCOSE-HOMEOSTASIS; EPITHELIAL-CELLS; TRANSGENIC MICE; LUMEN POLARITY; DIFFERENTIATION AB LKB1 is a key regulator of energy homeostasis through the activation of AMP-activated protein kinase (AMPK) and is functionally linked to vascular development, cell polarity, and tumor suppression. In humans, germ line LKB1 loss-of-function mutations cause Peutz-Jeghers syndrome (PJS), which is characterized by a predisposition to gastrointestinal neoplasms marked by a high risk of pancreatic cancer. To explore the developmental and physiological functions of Lkb1 in vivo, we examined the impact of conditional Lkb1 deletion in the pancreatic epithelium of the mouse. The Lkb1-deficient pancreas, although grossly normal at birth, demonstrates a defective acinar cell polarity, an abnormal cytoskeletal organization, a loss of tight junctions, and an inactivation of the AMPK/MARK/SAD family kinases. Rapid and progressive postnatal acinar cell degeneration and acinar-to-ductal metaplasia occur, culminating in marked pancreatic insufficiency and the development of pancreatic serous cystadenomas, a tumor type associated with PJS. Lkb1 deficiency also impacts the pancreas endocrine compartment, characterized by smaller and scattered islets and transient alterations in glucose control. These genetic studies provide in vivo evidence of a key role for LKB1 in the establishment of epithelial cell polarity that is vital for pancreatic acinar cell function and viability and for the suppression of neoplasia. C1 [Hezel, Aram F.; Chu, Gerry C.; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hezel, Aram F.; Gurumurthy, Sushma; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hezel, Aram F.; Gurumurthy, Sushma; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Granot, Zvi; Swisa, Avital; Dor, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cellular Biochem & Human Genet, IL-91010 Jerusalem, Israel. [Chu, Gerry C.; Bailey, Gerald] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chu, Gerry C.; DePinho, Ronald A.] Belfer Fdn, Inst Innovat Canc Sci, Ctr Appl Can Sci, Boston, MA USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Bardeesy, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Simches Res Bldg,CPZN 4216,185 Cambridge St, Boston, MA 02114 USA. EM nelbardeesy@partners.org; ron_depinho@dfci.harvard.edu RI Dor, Yuval/C-2405-2011 FU NCI NIH HHS [K08CA122835, K01 CA104647, K01CA104647, K08 CA122835, P01 CA117969, P01 CA117969-01, P01CA117969-03, U01 CA084313, U01CA084313-09] NR 53 TC 99 Z9 101 U1 2 U2 10 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 APR PY 2008 VL 28 IS 7 BP 2414 EP 2425 DI 10.1128/MCB.01621-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 276ZE UT WOS:000254181400026 PM 18227155 ER PT J AU Quinlan, MP Quatela, SE Philips, MR Settleman, J AF Quinlan, Margaret P. Quatela, Steven E. Philips, Mark R. Settleman, Jeffrey TI Activated kras, but not hras or nras, may initiate tumors of endodermal origin via stem cell expansion SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID EMBRYONAL CARCINOMA-CELLS; RAS GENE-MUTATIONS; K-RAS; RETINOIC ACID; CANCER-THERAPY; H-RAS; PRIMITIVE ENDODERM; PLASMA-MEMBRANE; N-RAS; NEOPLASTIC TRANSFORMATION AB The three closely related human Ras genes, Hras, Nras, and Kras, are all widely expressed, engage a common set of downstream effectors, and can each exhibit oncogenic activity. However, the vast majority of activating Ras mutations in human tumors involve Kras. Moreover, Kras mutations are most frequently seen in tumors of endodermally derived tissues (lung, pancreas, and colon), suggesting that activated Kras may affect an endodermal progenitor to initiate oncogenesis. Using a culture model of retinoic acid (RA)-induced stem cell differentiation to endoderm, we determined that while activated HrasV12 promotes differentiation and growth arrest in these endodermal progenitors, KrasV12 promotes their proliferation. Furthermore, KrasV12-expressing endodermal progenitors fail to differentiate upon RA treatment and continue to proliferate and maintain stem cell characteristics. NrasV12 neither promotes nor prevents differentiation. A structure-function analysis demonstrated that these distinct effects of the Ras isoforms involve their variable C-terminal domains, implicating compartmentalized signaling, and revealed a requirement for several established Ras effectors. These findings indicate that activated Ras isoforms exert profoundly different effects on endodermal progenitors and that mutant Kras may initiate tumorigenesis by expanding a susceptible stem/progenitor cell population. These results potentially explain the high frequency of Kras mutations in tumors of endodermal origin. C1 [Quinlan, Margaret P.; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Quinlan, Margaret P.; Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Quatela, Steven E.; Philips, Mark R.] NYU, Med Ctr, Dept Med, New York, NY 10016 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA109447, R01 CA109447-03] NR 101 TC 40 Z9 42 U1 1 U2 24 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 APR PY 2008 VL 28 IS 8 BP 2659 EP 2674 DI 10.1128/MCB.01661-07 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284LS UT WOS:000254708500015 PM 18268007 ER PT J AU Woo, AJ Moran, TB Schindler, YL Choe, SK Langer, NB Sullivan, MR Fujiwara, Y Paw, BH Cantor, AB AF Woo, Andrew J. Moran, Tyler B. Schindler, Yocheved L. Choe, Seong-Kyu Langer, Nathaniel B. Sullivan, Matthew R. Fujiwara, Yuko Paw, Barry H. Cantor, Alan B. TI Identification of ZBP-89 as a novel GATA-1-Associated transcription factor involved in megakaryocytic and erythroid development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; EMBRYONIC STEM-CELLS; FACTOR GATA-1; GENE-EXPRESSION; DNA-BINDING; MAMMALIAN-CELLS; DIFFERENTIATION; MICE; FOG; FAMILY AB A complete understanding of the transcriptional regulation of developmental lineages requires that all relevant factors be identified. Here, we have taken a proteomic approach to identify novel proteins associated with GATA-1, a lineage-restricted zinc finger transcription factor required for terminal erythroid and megakaryocytic maturation. We identify the Kriippet-type zinc finger transcription factor ZBP-89 as being a component of multiprotein complexes involving GATA-1 and its essential cofactor Friend of GATA-1 (FOG-1). Using chromatin immunoprecipitation assays, we show that GATA-1 and ZBP-89 cooccupy cis-regulatory elements of certain erythroid and megakaryocyte- specific genes, including an enhancer of the GATA-I gene itself. Loss-of-function studies in zebrafish and mice demonstrate an in vivo requirement for ZBP-89 in megakaryopoiesis and definitive erythropoiesis but not primitive erythropoiesis, phenocopying aspects of FOG-1- and GATA-1-deficient animals. These findings identify ZBP-89 as being a novel transcription factor involved in erythroid and megakaryocytic development and suggest that it serves a cooperative function with GATA-I and/or FOG-1 in a developmental stage-specific manner. C1 [Woo, Andrew J.; Moran, Tyler B.; Schindler, Yocheved L.; Sullivan, Matthew R.; Fujiwara, Yuko; Cantor, Alan B.] Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Choe, Seong-Kyu; Langer, Nathaniel B.; Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RP Cantor, AB (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu FU NHLBI NIH HHS [R01 HL 075705, R01 HL075705]; NIDDK NIH HHS [R01 DK070838] NR 64 TC 43 Z9 45 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2008 VL 28 IS 8 BP 2675 EP 2689 DI 10.1128/MCB.01945-07 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284LS UT WOS:000254708500016 PM 18250154 ER PT J AU Wang, HX Xu, Q Fang, X Yong, J Wu, ZG AF Wang, Haixia Xu, Qing Fang Xiao Yong Jiang Wu, Zhenguo TI Involvement of the p38 mitogen-activated protein kinase alpha, beta, and gamma isoforms in myogenic differentiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SKELETAL-MUSCLE DIFFERENTIATION; MYOBLAST DIFFERENTIATION; TRANSCRIPTION FACTORS; GENE-TRANSCRIPTION; GROWTH-FACTOR; E2F FAMILY; CELL-CYCLE; EXPRESSION; PATHWAY; MYOD AB We and others previously showed that p38 mitogen-activated protein kinase is indispensable for myogenic differentiation. However, it is less clear which of the four p38 isoforms in the mouse genome participates in this process. Using C2C12 myogenic cells as a model, we showed here that p38 alpha, beta, and gamma are expressed with distinct expression patterns during differentiation. Knockdown of any of them by small interfering RNA inhibits myogenic differentiation, which suggests that the functions of the three p38 isoforms are not completely redundant. To further elucidate the unique role of each p38 isoform in myogenic differentiation, we individually knocked down one p38 isoform at a time in C2C12 cells, and we compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, whereas others are uniquely regulated by one particular p38 isoform. Furthermore, several novel p38 target genes (i.e., E2F2, cyclin D3, and WISP1) are found to be required for myogenin expression, which provides a molecular basis to explain why different p38 isoforms are required for myogenic differentiation. C1 [Yong Jiang] So Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. [Wang, Haixia; Fang Xiao; Wu, Zhenguo] Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. [Xu, Qing] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yong, J (reprint author), So Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. EM jiang48231@163.com; bczgwu@ust.hk FU Hong Kong Research Grant Council [HKUST6412/05M, HKUST6496/06M, CA06/07.SC02]; Area of Excellence Scheme [AoE/B-15/01]; Ministry of Science and Technology of China [2002 CB513005] FX We thank Dr. J. Han for p38 expression vectors, Dr. J. R. Nevins (Duke University) for E2F2 expression vector, Dr. M. A. Bogoyevitch for p38 gamma antibody, and Carol Wong for technical assistance. This project is supported by Hong Kong Research Grant Council grants HKUST6412/05M, HKUST6496/06M, and CA06/07.SC02 (to Z.W.); Area of Excellence Scheme AoE/B-15/01; and a 973 project from the Ministry of Science and Technology of China (2002 CB513005) ( o Z.W. and Y.J.). NR 33 TC 22 Z9 22 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2008 VL 19 IS 4 BP 1519 EP 1528 DI 10.1091/mbc.E07-08-0817 PG 10 WC Cell Biology SC Cell Biology GA 344TZ UT WOS:000258951500022 PM 18256287 ER PT J AU Kono, K Nogami, S Abe, M Nishizawa, M Morishita, S Pellman, D Ohya, Y AF Kono, Keiko Nogami, Satoru Abe, Mitsuhiro Nishizawa, Masafumi Morishita, Shinichi Pellman, David Ohya, Yoshikazu TI G1/S cyclin-dependent kinase regulates small GTPase Rho1p through phosphorylation of RhoGEF Tus1p in Saccharomyces cerevisiae SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID POLARIZED CELL-GROWTH; EXCHANGE FACTOR ROM2; BUDDING YEAST; BINDING PROTEIN; MAP-KINASE; ACTIN CYTOSKELETON; MORPHOGENESIS; ACTIVATION; CYTOKINESIS; NUCLEATION AB Rho1p is an essential small GTPase that plays a key role in the morphogenesis of Saccharomyces cerevisiae. We show here that the activation of Rho1p is regulated by a cyclin-dependent kinase (CDK). Rho1p is activated at the G1/S transition at the incipient-bud sites by the Cln2p (G1 cyclin) and Cdc28p (CDK) complex, in a process mediated by Tus1p, a guanine nucleotide exchange factor for Rho1p. Tus1p interacts physically with Cln2p/Cdc28p and is phosphorylated in a Cln2p/ Cdc28p-dependent manner. CDK phosphorylation consensus sites in Tus1p are required for both Cln2p-dependent activation of Rho1p and polarized organization of the actin cytoskeleton. We propose that Cln2p/Cdc28p-dependent phosphorylation of Tus1p is required for appropriate temporal and spatial activation of Rho1p at the G1/S transition. C1 [Morishita, Shinichi] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol, Chiba 2778562, Japan. [Kono, Keiko; Nogami, Satoru; Abe, Mitsuhiro; Ohya, Yoshikazu] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan. [Kono, Keiko; Pellman, David] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kono, Keiko; Pellman, David] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Kono, Keiko; Pellman, David] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nishizawa, Masafumi] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan. RP Ohya, Y (reprint author), Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan. EM ohya@k.u-tokyo.ac.jp RI Nogami, Satoru/G-6061-2014 OI Nogami, Satoru/0000-0002-4517-0180 FU Ministry of Education, Science, Sports, and Culture of Japan [16026205]; Institute for Bioinformatics and Research and Development of the Japan Science and Technology Corporation FX We thank K. M. Shokat (University of California, San Francisco) for the kind gift of 1-NM-PP1, S. Buttery for reviewing manuscript, and S. Yoshida and S. Bartolini for constructing plasmids and primers and helpful comments throughout this study. This work was supported by a grant (16026205) for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan and by the Institute for Bioinformatics and Research and Development of the Japan Science and Technology Corporation. NR 58 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2008 VL 19 IS 4 BP 1763 EP 1771 DI 10.1091/mbc.E07-09-0950 PG 9 WC Cell Biology SC Cell Biology GA 344TZ UT WOS:000258951500044 PM 18256282 ER PT J AU Godin-Heymann, N LlIkus, L Brannigan, BW McDermott, U Lamb, J Maheswaran, S Settleman, J Haber, DA AF Godin-Heymann, Nadia LlIkus, Lindsey Brannigan, Brian W. McDermott, Ultan Lamb, Jennifer Maheswaran, Shyamala Settleman, Jeffrey Haber, Daniel A. TI The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; KINASE DOMAIN; ACQUIRED-RESISTANCE; TYROSINE KINASE; GEFITINIB; THERAPY; AMPLIFICATION; ERLOTINIB; HKI-272 AB Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) kinase domain tend to respond well to the tyrosine kinase inhibitors, gefitinib and erlotinib. However, following clinical response, these patients typically relapse within a year of treatment. In many cases, resistance is caused by an acquired secondary EGFR kinase domain mutation, T790M. In vitro studies have shown that a new class of EGFR-irreversible inhibitors could overcome the resistance conferred by T790M. Clinical trials are under way to examine the efficacy of one of these inhibitors, HKI-272, in patients with NSCLC who initially responded to gefitinib/erlotinib and subsequently relapsed. To anticipate the possibility that patients who respond to irreversible inhibitors will develop secondary resistance to such inhibitors, as has been seen in other similar settings, we modeled acquired resistance to the dual EGFR/HER2-irreversible tyrosine kinase inhibitor HKI-272 in a NSCLC cell culture model. We found that HKI-272-resistant clones fall into two biochemical groups based on the retention of EGFR phosphorylation in the presence of the drug.. Cells that retain phosphorylated EGFR have acquired the secondary mutation T790M. Moreover, HKI-272 can overcome T790M resistance only at supra-pharmacologic concentrations. We further model mutations at EGFR C797 as a mechanism of resistance to irreversible EGFR inhibitors and show that although these mutants are resistant to the irreversible inhibitor, they retain erlotinib sensitivity. Our findings suggest that HKI-272 treatment at maximally tolerated dosing may lead to the emergence of T790M-mediated resistance, whereas treatment with a more potent irreversible inhibitor could yield a resistance mutation at EGFR C797. C1 [Haber, Daniel A.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu OI McDermott, Ultan/0000-0001-9032-4700 FU NCI NIH HHS [P01 CA95281, R01 CA115830-02] NR 20 TC 122 Z9 126 U1 1 U2 14 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 APR PY 2008 VL 7 IS 4 BP 874 EP 879 DI 10.1158/1535-7163.MCT-07-2387 PG 6 WC Oncology SC Oncology GA 288SW UT WOS:000255007100015 PM 18413800 ER PT J AU Drouin, EE Glickstein, L Kwok, WW Nepom, GT Steere, AC AF Drouin, Elise E. Glickstein, Lisa Kwok, William W. Nepom, Gerald T. Steere, Allen C. TI Searching for borrelial T cell epitopes associated with antibiotic-refractory Lyme arthritis SO MOLECULAR IMMUNOLOGY LA English DT Article DE Lyme arthritis; Borrelia burgdorferi; T cell epitope; MHC molecule; TEPITOPE ID SURFACE PROTEIN-A; ANTIBODY-RESPONSE; PEPTIDE ANTIGENS; BURGDORFERI DNA; DISEASE; IDENTIFICATION; SERODIAGNOSIS; AUTOIMMUNITY; RECOMBINANT; MOLECULES AB Antibiotic-refractory Lyme arthritis is believed to result from an infection-induced autoimmune response triggered by the spirochete Borrelia burgdorferi (Bb). Disease susceptibility is associated with the HLA alleles DRB1*0101, 0401, 0402, 0404, 0405 and DRB5*0101, and all these MHC molecules bind the Bb epitope OspA(163-175). However, not all patients have a proliferative response to this epitope. To identify other possible Bb epitopes involved in this disease process, the algorithm TEPITOPE was used to scan 17 immunogenic Bb proteins for potential T cell epitopes with a refractory arthritis-associated MHC binding profile, and the Bb proteome was searched for peptides with sequence homology to OspA(165-173). Sixteen promising T epitopes were identified and their MHC binding profiles to 13 MHC molecules were verified using in vitro MHC/peptide binding assays. One peptide, BBK32(392-404), had a strong refractory arthritis-associated MHC binding profile, and another GK(297-306) shared sequence homology to OspA(165-173). However, patient cells did not proliferate in response to either peptide making it highly unlikely they were involved in a refractory course. A comparison of the in silico and in vitro results revealed that TEPITOPE correctly predicted 74% of the in vitro binding peptides, but it incorrectly predicted that 44% of the in vitro nonbinding peptides would bind. For a particular MHC molecule, concordance between the in silico and in vitro results varied anywhere between 33% and 100%. Therefore, while additional Bb epitopes may be involved in the development of antibiotic-refractory Lyme arthritis, recognition of OspA(163-175) remains the only known Bb epitope associated with this disease course. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Drouin, Elise E.; Glickstein, Lisa; Steere, Allen C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Kwok, William W.; Nepom, Gerald T.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. RP Drouin, EE (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM edrouin@partners.org OI Nepom, Gerald/0000-0002-8063-1464 FU NIAMS NIH HHS [AR-20358, R01 AR020358-31, R01 AR020358, R01 AR020358-32A1] NR 30 TC 18 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 2008 VL 45 IS 8 BP 2323 EP 2332 DI 10.1016/j.molimm.2007.11.010 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 287UQ UT WOS:000254942400022 PM 18191206 ER PT J AU Yildirim, MA Vidal, M AF Yildirim, Muhammed A. Vidal, Marc TI Systems engineering to systems biology SO MOLECULAR SYSTEMS BIOLOGY LA English DT Editorial Material AB This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivative works is permitted but the resulting work may be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission. C1 [Yildirim, Muhammed A.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yildirim, Muhammed A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Yildirim, Muhammed A.; Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, CTr Canc Syst Biol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, CTr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Yildirim, Muhammed/J-3695-2014 OI Yildirim, Muhammed/0000-0003-2826-1766 NR 3 TC 4 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD APR PY 2008 VL 4 AR 185 DI 10.1038/msb.2008.22 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 296MU UT WOS:000255551300006 PM 18414486 ER PT J AU Pruett-Miller, SM Connelly, JP Maeder, ML Joung, JK Porteus, MH AF Pruett-Miller, Shondra M. Connelly, Jon P. Maeder, Morgan L. Joung, J. Keith Porteus, Matthew H. TI Comparison of zinc finger nucleases for use in gene targeting in mammalian cells SO MOLECULAR THERAPY LA English DT Article ID DOUBLE-STRAND BREAKS; ARTIFICIAL TRANSCRIPTION FACTORS; CHIMERIC RESTRICTION ENZYMES; HOMOLOGOUS RECOMBINATION; DNA-RECOGNITION; ADENOASSOCIATED VIRUS; BUILDING-BLOCKS; PROTEINS; CONSTRUCTION; CLEAVAGE AB Homologous recombination is a technique used for performing precise genomic manipulations, and this makes it potentially ideal for gene therapy. The rate of spontaneous homologous recombination in human cells has been too low to be used experimentally or therapeutically but, by inducing a DNA double-strand break (DSB) in the target gene this rate can be stimulated. Zinc finger nucleases (ZFNs) are synthetic fusion proteins that can induce DSBs at specific sequences of DNA and stimulate gene targeting. Although the success of ZFNs in this application has been demonstrated, several issues remain. First, an optimal, generalized method of making effective and safe ZFNs needs to be determined. Second, a systematic method of evaluating the efficiency and safety of ZFNs is needed. We compared the gene-targeting efficiencies and cytotoxicity of ZFNs made using modular-assembly and ZFNs made using a bacterial 2-hybrid (B2H) selection-based method, in each case targeting the same single site. We found that a ZFN pair made using the B2H strategy is more efficient at stimulating gene targeting and less toxic than a pair made using modular-assembly. We demonstrate that a pair of three-finger B2H ZFNs is as efficient at stimulating gene targeting as ZFNs with more fingers, and induce similar or lower rates of toxicity. C1 [Pruett-Miller, Shondra M.; Connelly, Jon P.; Porteus, Matthew H.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Pruett-Miller, Shondra M.; Connelly, Jon P.; Porteus, Matthew H.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Porteus, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM matthew.porteus@utsouthwestern.edu FU NHLBI NIH HHS [K08 HL070268, R01 HL079295]; NIGMS NIH HHS [R01 GM069906]; NIH HHS [DP1 OD006862] NR 50 TC 77 Z9 79 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2008 VL 16 IS 4 BP 707 EP 717 DI 10.1038/mt.2008.20 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 287PS UT WOS:000254929600014 PM 18334988 ER PT J AU Engelhorn, ME Guevara-Patino, JA Merghoub, T Liu, C Ferrone, CR Rizzuto, GA Cymerman, DH Posnett, DN Houghton, AN Wolchok, JD AF Engelhorn, Manuel E. Guevara-Patino, Jose A. Merghoub, Taha Liu, Cailian Ferrone, Cristina R. Rizzuto, Gabrielle A. Cymerman, Daniel Hirschhorn Posnett, David N. Houghton, Alan N. Wolchok, Jedd D. TI Mechanisms of immunization against cancer using chimeric antigens SO MOLECULAR THERAPY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CELLULAR IMMUNE-RESPONSES; CLASS-I PRESENTATION; DNA VACCINE; DENDRITIC CELLS; TUMOR-IMMUNITY; T-LYMPHOCYTES; INTERCELLULAR TRAFFICKING; SELF ANTIGEN; EXOTOXIN-A AB Successful approaches to tumor immunotherapy must overcome the physiological state of tolerance of the immune system to self-tumor antigens. Immunization with appropriate variants of syngeneic antigens can achieve this. However, improvements in vaccine design are needed for efficient cancer immunotherapy. Here we explore nine different chimeric vaccine designs, in which the antigen of interest is expressed as an in-frame fusion with polypeptides that impact antigen processing or presentation. In DNA immunization experiments in mice, three of nine fusions elevated relevant CD8(+) T-cell responses and tumor protection relative to an unfused melanoma antigen. These fusions were: Escherichia coli outer membrane protein A (OmpA), Pseudomonas aeruginosa exotoxin A, and VP22 protein of herpes simplex virus-1. The gains of immunogenicity conferred by the latter two are independent of epitope presentation by major histocompatibility complex class II (MHC II). This finding has positive implications for immunotherapy in individuals with CD4(+) T-cell deficiencies. We present evidence that antigen instability is not a sine qua non condition for immunogenicity. Experiments using two additional melanoma antigens identified different optimal fusion partners, thereby indicating that the benefits of fusion vectors remain antigen specific. Therefore large fusion vector panels such as those presented here can provide information to promote the successful advancement of gene-based vaccines. C1 [Engelhorn, Manuel E.; Merghoub, Taha; Liu, Cailian; Rizzuto, Gabrielle A.; Cymerman, Daniel Hirschhorn; Posnett, David N.; Houghton, Alan N.; Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Melanoma Sarcoma Serv, Ludwig Ctr Canc Immunotherapy, Swim Across Amer Lab,Dept Med, New York, NY 10021 USA. [Guevara-Patino, Jose A.] Univ Chicago, Sect Surg, Chicago, IL 60637 USA. [Guevara-Patino, Jose A.] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. [Ferrone, Cristina R.] Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. RP Wolchok, JD (reprint author), Mem Sloan Kettering Canc Ctr, Melanoma Sarcoma Serv, Ludwig Ctr Canc Immunotherapy, Swim Across Amer Lab,Dept Med, 1275 York Ave,Room Z-1462, New York, NY 10021 USA. EM wolchokj@mskcc.org FU NCI NIH HHS [P01CA33049, P01 CA033049, P01 CA059350, P01CA59350, R01 CA056821, R01CA56821] NR 50 TC 12 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2008 VL 16 IS 4 BP 773 EP 781 DI 10.1038/mt.2008.8 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 287PS UT WOS:000254929600022 PM 18301399 ER PT J AU Travassos, LR Rodrigues, EG Iwai, LK Taborda, CP AF Travassos, Luiz R. Rodrigues, Elaine G. Iwai, Leo K. Taborda, Carlos P. TI Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy SO MYCOPATHOLOGIA LA English DT Article DE paracoccidioidomycosis; Paracoccidioides brasiliensis; peptide vaccine; gp43; P10; chemotherapy ID T-CELL EPITOPE; CANDIDA-ALBICANS; HISTOPLASMA-CAPSULATUM; THERAPEUTIC ACTIVITY; FUNGAL DISEASES; DENDRITIC CELLS; BRASILIENSIS; ANTIBODY; INFECTION; GP43 AB Chemotherapy is the basis of treatment of paracoccidioidomycosis in its various forms. Depending on the Paracoccidioides brasiliensis virulence, the status of host immunity, the degree of tissue involvement and fungal dissemination, treatment can be extended for long periods with an alarming frequency of relapses. Association of chemotherapy with a vaccine to boost the cellular immune response seemed a relevant project not only to reduce the time of treatment but also to prevent relapses and improve the prognosis of anergic cases. The candidate immunogen is the gp43 major diagnostic antigen of P. brasiliensis and more specifically its derived peptide P10, carrying the CD4(+) T-cell epitope. Both gp43 and P10 protected Balb/c mice against intratracheal infections with virulent P. brasiliensis strain. P10 as single peptide or in a multiple-antigen-peptide (MAP) tetravalent construction was protective without adjuvant either by preimmunization and intratracheal challenge or as a therapeutic agent in mice with installed infection. P10 showed additive protective effects in drug-treated mice stimulating a Th-1 type immune response with high IFN-gamma and IL-12. P10 and few other peptides in the gp43 were selected by Tepitope algorithm and actually shown to promiscuously bind several prominent HLA-DR molecules suggesting that a peptide vaccine could be devised for a genetically heterogenous population. P10 was protective in animals turned anergic, was effective in a DNA minigene vaccine, and increased the protection by monoclonal antibodies in Balb/c mice. DNA vaccines and peptide vaccines are promising therapeutic tools to be explored in the control of systemic mycoses. C1 [Travassos, Luiz R.; Rodrigues, Elaine G.] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit, BR-04023062 Sao Paulo, Brazil. [Iwai, Leo K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. [Taborda, Carlos P.] Univ Sao Paulo, Dept Microbiol, Sao Paulo, Brazil. RP Travassos, LR (reprint author), Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit, Rua Botucatu 862,8 Andar, BR-04023062 Sao Paulo, Brazil. EM travassos@unifesp.br RI Travassos, Luiz/J-3631-2012; Iwai, Leo/M-1734-2013; Rodrigues, Elaine /H-3688-2014; Taborda, Carlos/K-1660-2016 OI Iwai, Leo/0000-0002-1571-7763; Taborda, Carlos/0000-0001-9928-9809 NR 50 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PD APR PY 2008 VL 165 IS 4-5 BP 341 EP 352 DI 10.1007/s11046-007-9056-1 PG 12 WC Mycology SC Mycology GA 292HC UT WOS:000255256100014 PM 18777638 ER PT J AU MacConaill, L Meyerson, M AF MacConaill, Laura Meyerson, Matthew TI Adding pathogens by genomic subtraction SO NATURE GENETICS LA English DT Editorial Material ID IDENTIFICATION; SEQUENCES AB Two studies report the application of high-throughput sequencing technologies to discover infectious agents associated with diseased human tissues. These findings herald a breakthrough in the field of pathogen discovery. C1 [MacConaill, Laura; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [MacConaill, Laura; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [MacConaill, Laura; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [MacConaill, Laura; Meyerson, Matthew] MIT, Cambridge, MA 02139 USA. [MacConaill, Laura; Meyerson, Matthew] Broad Inst Harvard, Cambridge, MA 02139 USA. RP MacConaill, L (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 15 TC 15 Z9 15 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2008 VL 40 IS 4 BP 380 EP 382 DI 10.1038/ng0408-380 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 279XG UT WOS:000254388100003 PM 18368124 ER PT J AU Puschendorf, M Terranova, R Boutsma, E Mao, XH Isono, KI Brykczynska, U Kolb, C Otte, AP Koseki, H Orkin, SH van Lohuizen, M Peters, AHFM AF Puschendorf, Mareike Terranova, Remi Boutsma, Erwin Mao, Xiaohong Isono, Kyo-ichi Brykczynska, Urszula Kolb, Carolin Otte, Arie P. Koseki, Haruhiko Orkin, Stuart H. van Lohuizen, Maarten Peters, Antoine H. F. M. TI PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos SO NATURE GENETICS LA English DT Article ID REPRESSIVE HISTONE METHYLATION; H3 LYSINE-9 METHYLATION; PERICENTRIC HETEROCHROMATIN; X-INACTIVATION; SATELLITE REPEATS; DNA METHYLATION; CLONED EMBRYOS; GROUP PROTEINS; POLYCOMB; CHROMATIN AB In eukaryotes, Suv39h H3K9 trimethyltransferases are required for pericentric heterochromatin formation and function. In early mouse preimplantation embryos, however, paternal pericentric heterochromatin lacks Suv39h-mediated H3K9me3 and downstream marks. Here we demonstrate Ezh2-independent targeting of maternally provided polycomb repressive complex 1 (PRC1) components to paternal heterochromatin. In Suv39h2 maternally deficient zygotes, PRC1 also associates with maternal heterochromatin lacking H3K9me3, thereby revealing hierarchy between repressive pathways. In Rnf2 maternally deficient zygotes, the PRC1 complex is disrupted, and levels of pericentric major satellite transcripts are increased at the paternal but not the maternal genome. We conclude that in early embryos, Suv39h-mediated H3K9me3 constitutes the dominant maternal transgenerational signal for pericentric heterochromatin formation. In absence of this signal, PRC1 functions as the default repressive back-up mechanism. Parental epigenetic asymmetry, also observed along cleavage chromosomes, is resolved by the end of the 8-cell stage-concurrent with blastomere polarization-marking the end of the maternal-to-embryonic transition. C1 [Puschendorf, Mareike; Terranova, Remi; Brykczynska, Urszula; Kolb, Carolin; Peters, Antoine H. F. M.] Friedrich Miescher Inst, CH-4058 Basel, Switzerland. [Boutsma, Erwin; van Lohuizen, Maarten] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. [Boutsma, Erwin; van Lohuizen, Maarten] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. [Mao, Xiaohong; Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Mao, Xiaohong; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Isono, Kyo-ichi; Koseki, Haruhiko] RIKEN Yokohama Inst, RIKEN Res Ctr Allergy & Immunol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Otte, Arie P.] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands. RP Peters, AHFM (reprint author), Friedrich Miescher Inst, Maulbeerst 66, CH-4058 Basel, Switzerland. EM antoine.peters@fmi.ch RI Koseki, Haruhiko/I-3825-2014 OI Koseki, Haruhiko/0000-0001-8424-5854 NR 49 TC 171 Z9 174 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2008 VL 40 IS 4 BP 411 EP 420 DI 10.1038/ng.99 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 279XG UT WOS:000254388100011 PM 18311137 ER PT J AU Katajisto, P Vaahtomeri, K Ekman, N Ventela, E Ristimaki, A Bardeesy, N Feil, R DePinho, RA Makela, TP AF Katajisto, Pekka Vaahtomeri, Kari Ekman, Niklas Ventela, Eeva Ristimaki, Ari Bardeesy, Nabeel Feil, Robert DePinho, Ronald A. Makela, Tomi P. TI LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis SO NATURE GENETICS LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; SMOOTH-MUSCLE; GROWTH-FACTORS; TGF-BETA; DIFFERENTIATION; FIBROBLASTS; CANCER; MYOFIBROBLASTS; LUNG AB Germline mutations in STK11 (also known as LKB1) are found in individuals with Peutz-Jeghers syndrome (PJS)(1) manifesting with gastrointestinal polyps that contain a prominent stromal component. Epithelia in polyps of Stk11(+/-) mice can retain a functional copy of Stk11 (refs. 2,3), and loss of heterozygosity is not an obligate feature of human polyps(4), raising the possibility of non-epithelial origins in tumorigenesis. Here we show that either monoallelic or biallelic loss of murine Stk11 limited to Tagln-expressing mesenchymal cells results in premature postnatal death as a result of gastrointestinal polyps indistinguishable from those in PJS. Stk11-deficient mesenchymal cells produced less TGF beta, and defective TGF beta signaling to epithelial cells coincided with epithelial proliferation. We also noted TGF beta signaling defects in polyps of individuals with PJS, suggesting that the identified stromal-derived mechanism of tumor suppression is also relevant in PJS. C1 [Katajisto, Pekka; Vaahtomeri, Kari; Ekman, Niklas; Ventela, Eeva; Ristimaki, Ari; Makela, Tomi P.] Univ Helsinki, Genome Scale Biol Program, FIN-00014 Helsinki, Finland. [Katajisto, Pekka; Vaahtomeri, Kari; Ekman, Niklas; Ventela, Eeva; Ristimaki, Ari; Makela, Tomi P.] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland. [Ristimaki, Ari] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. [Feil, Robert] Univ Tubingen, Interfak Inst Biochem, D-72076 Tubingen, Germany. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Ctr Appl Canc Sci Belfer Inst Inno, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Ctr Appl Canc Sci Belfer Inst Innovat Ca, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet,Ctr Appl Canc Sci Belfer Inst Innovat, Boston, MA 02115 USA. RP Makela, TP (reprint author), Univ Helsinki, Genome Scale Biol Program, FIN-00014 Helsinki, Finland. EM tomi.makela@helsinki.fi RI makela, tomi/B-3734-2009; Feil, Robert/B-8918-2014; OI makela, tomi/0000-0002-4869-8044; Feil, Robert/0000-0002-7335-4841; Vaahtomeri, Kari/0000-0001-7829-3518 NR 25 TC 59 Z9 66 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2008 VL 40 IS 4 BP 455 EP 459 DI 10.1038/ng.98 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 279XG UT WOS:000254388100017 PM 18311138 ER PT J AU Kagan, JC Su, T Horng, T Chow, A Akira, S Medzhitov, R AF Kagan, Jonathan C. Su, Tian Horng, Tiffany Chow, Amy Akira, Shizuo Medzhitov, Ruslan TI TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta SO NATURE IMMUNOLOGY LA English DT Article ID DEPENDENT IMMUNE-RESPONSES; TOLL-LIKE RECEPTORS; NF-KAPPA-B; ADAPTER MOLECULE; SIGNALING PATHWAY; STRANDED-RNA; IFN-BETA; RECOGNITION; ACTIVATION; INNATE AB Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organized around endocytosis of the TLR4 complex. We propose that TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes. Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location. C1 [Kagan, Jonathan C.; Su, Tian; Horng, Tiffany; Chow, Amy; Medzhitov, Ruslan] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Kagan, Jonathan C.; Su, Tian; Horng, Tiffany; Chow, Amy; Medzhitov, Ruslan] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. [Akira, Shizuo] Osaka Univ, Japan Sci & Technol Agcy, ERATO, Microbial Dis Res Inst,Dept Host Def, Osaka, Japan. [Horng, Tiffany] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. [Chow, Amy] Rochester Inst Technol, Dept Biol Sci, Rochester, NY 14623 USA. RP Kagan, JC (reprint author), Childrens Hosp, GI Cell Biol, 300 Longwood Ave, Boston, MA 02115 USA. EM jonathan.kagan@childrens.harvard.edu; ruslan.medzhitov@yale.edu RI Akira, Shizuo/C-3134-2009 FU Howard Hughes Medical Institute; NIAID NIH HHS [1K99AI072955-01, AI 061360, K99 AI072955, K99 AI072955-01, P01 AI044220, P01 AI44220, R00 AI072955, R00 AI072955-02, R01 AI046688, R37 AI046688, U01 AI061360] NR 50 TC 581 Z9 604 U1 1 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2008 VL 9 IS 4 BP 361 EP 368 DI 10.1038/ni1569 PG 8 WC Immunology SC Immunology GA 276ED UT WOS:000254123200011 PM 18297073 ER PT J AU Xiao, CC Srinivasan, L Calado, DP Patterson, HC Zhang, BC Wang, J Henderson, JM Kutok, JL Rajewsky, K AF Xiao, Changchun Srinivasan, Lakshmi Calado, Dinis Pedro Patterson, Heide Christine Zhang, Baochun Wang, Jing Henderson, Joel M. Kutok, Jeffrey L. Rajewsky, Klaus TI Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes SO NATURE IMMUNOLOGY LA English DT Article ID KAPPA-B ACTIVITY; CELL PROLIFERATION; MALIGNANT-LYMPHOMA; MICRORNA TARGETS; FEEDBACK LOOP; MUTATION; APOPTOSIS; GENE; BIM; AMPLIFICATION AB The genomic region encoding the miR-17-92 microRNA ( miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region. C1 [Xiao, Changchun; Srinivasan, Lakshmi; Calado, Dinis Pedro; Patterson, Heide Christine; Zhang, Baochun; Wang, Jing; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Henderson, Joel M.; Kutok, Jeffrey L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu OI Zhang, Baochun/0000-0003-1759-1161 FU NIAID NIH HHS [R01 AI064345-02, AI064345, R01 AI064345, R01 AI064345-01, R01 AI064345-03] NR 49 TC 711 Z9 753 U1 9 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2008 VL 9 IS 4 BP 405 EP 414 DI 10.1038/ni1575 PG 10 WC Immunology SC Immunology GA 276ED UT WOS:000254123200016 PM 18327259 ER PT J AU Oh-Hora, M Yamashita, M Hogan, PG Sharma, S Lamperti, E Chung, W Prakriya, M Feske, S Rao, A AF Oh-hora, Masatsugu Yamashita, Megumi Hogan, Patrick G. Sharma, Sonia Lamperti, Ed Chung, Woo Prakriya, Murali Feske, Stefan Rao, Anjana TI Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance SO NATURE IMMUNOLOGY LA English DT Article ID OPERATED CA2+ ENTRY; STROMAL INTERACTION MOLECULE-1; NF-KAPPA-B; PLASMA-MEMBRANE; CRAC CHANNEL; STORE DEPLETION; AUTOIMMUNE-DISEASE; TYROSINE RESIDUES; NUCLEAR FACTOR; LYMPHOCYTES AB Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell-specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells. C1 [Oh-hora, Masatsugu; Hogan, Patrick G.; Sharma, Sonia; Lamperti, Ed; Feske, Stefan; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. [Yamashita, Megumi; Chung, Woo; Prakriya, Murali] Northwestern Univ, Feinberg Sch Med, Dept Biol Chem & Mol Pharmacol, Chicago, IL 60611 USA. [Oh-hora, Masatsugu; Hogan, Patrick G.; Sharma, Sonia; Lamperti, Ed; Feske, Stefan; Rao, Anjana] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Feske, S (reprint author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. EM stefan.feske@med.nyu.edu; arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [R01 AI040127-17, R01 AI040127, R01 AI048213, R01 AI048213-08]; NIGMS NIH HHS [R01 GM075256, R01 GM075256-03]; NINDS NIH HHS [R01 NS057499, R01 NS057499-01, R01 NS057499-02] NR 67 TC 284 Z9 289 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2008 VL 9 IS 4 BP 432 EP 443 DI 10.1038/ni1574 PG 12 WC Immunology SC Immunology GA 276ED UT WOS:000254123200019 PM 18327260 ER PT J AU Ahuja, SK Kulkarni, H Catano, G Agan, BK Camargo, JF He, W O'Connell, RJ Marconi, VC Delmar, J Eron, J Clark, RA Frost, S Martin, J Ahuja, SS Deeks, SG Little, S Richman, D Hecht, FM Dolan, MJ AF Ahuja, Sunil K. Kulkarni, Hemant Catano, Gabriel Agan, Brian K. Camargo, Jose F. He, Weijing O'Connell, Robert J. Marconi, Vincent C. Delmar, Judith Eron, Joseph Clark, Robert A. Frost, Simon Martin, Jeffrey Ahuja, Seema S. Deeks, Steven G. Little, Susan Richman, Douglas Hecht, Frederick M. Dolan, Matthew J. TI CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED ADULTS; CD4(+) CELL COUNT; PLASMA VIRAL LOAD; DISEASE PROGRESSION; VIROLOGICAL SUPPRESSION; GENETIC PROFILES; RNA LEVEL; AIDS; MORTALITY AB The basis for the extensive variability seen in the reconstitution of CD4(+) T cell counts in HIV- infected individuals receiving highly active antiretroviral therapy ( HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4(+) T cells/ mm(3). The CCL3L1- CCR5 genotypes favoring CD4(+) T cell recovery are similar to those that blunted CD4(+) T cell depletion during the time before HAART became available ( pre- HAART era), suggesting that a common CCL3L1- CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4(+) cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. C1 [Ahuja, Sunil K.; Kulkarni, Hemant; Catano, Gabriel; Camargo, Jose F.; He, Weijing; Clark, Robert A.; Ahuja, Seema S.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV1 Infect, San Antonio, TX 78229 USA. [Ahuja, Sunil K.; Kulkarni, Hemant; Catano, Gabriel; Camargo, Jose F.; He, Weijing; Clark, Robert A.; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Agan, Brian K.; O'Connell, Robert J.; Marconi, Vincent C.; Delmar, Judith; Dolan, Matthew J.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Agan, Brian K.; O'Connell, Robert J.; Marconi, Vincent C.; Delmar, Judith; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. [Agan, Brian K.; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Agan, Brian K.; Marconi, Vincent C.; Delmar, Judith; Dolan, Matthew J.] San Antonio Mil Med Ctr, Ft Sam Houston, TX 78234 USA. [Eron, Joseph] Univ N Carolina, Chapel Hill, NC 27599 USA. [Frost, Simon; Little, Susan; Richman, Douglas] Univ Calif San Diego, Antiviral Res Ctr, Dept Med, San Diego, CA 92103 USA. [Frost, Simon; Richman, Douglas] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. [Martin, Jeffrey] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Deeks, Steven G.; Hecht, Frederick M.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. RP Ahuja, SK (reprint author), S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV1 Infect, 7400 Merton Minister, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu; mdolan@hjf.org RI Frost, Simon/F-3648-2010; Marconi, Vincent/N-3210-2014; OI Frost, Simon/0000-0002-5207-9879; Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669 FU NIAID NIH HHS [P01 AI074621, P01 AI074621-01A10002, P30 AI050410] NR 50 TC 84 Z9 86 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2008 VL 14 IS 4 BP 413 EP 420 DI 10.1038/nm1741 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 283ZD UT WOS:000254674100028 PM 18376407 ER PT J AU Vasudevan, A Long, JE Crandall, JE Rubenstein, JLR Bhide, PG AF Vasudevan, Anju Long, Jason E. Crandall, James E. Rubenstein, John L. R. Bhide, Pradeep G. TI Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain SO NATURE NEUROSCIENCE LA English DT Article ID MOUSE CORPUS STRIATUM; NEURAL-TUBE; VENTRAL FOREBRAIN; BASAL FOREBRAIN; GENE-EXPRESSION; CELL-CYCLE; DLX GENES; TELENCEPHALON; DIFFERENTIATION; MECHANISMS AB Prevailing notions of cerebral vascularization imply that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations. Endothelial cells, building blocks of blood vessels, are thought to be homogeneous in the brain with respect to their origins, gene expression patterns and developmental mechanisms. These current notions that cerebral angiogenesis is regulated by local environmental signals contrast with current models of cell-autonomous regulation of neuronal development. Here we demonstrate that telencephalic angiogenesis in mice progresses in an orderly, ventral-to-dorsal gradient regulated by compartment-specific homeobox transcription factors. Our data offer new perspectives on intrinsic regulation of angiogenesis in the embryonic telencephalon, call for a revision of the current models of telencephalic angiogenesis and support novel roles for endothelial cells in brain development. C1 [Vasudevan, Anju; Bhide, Pradeep G.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Vasudevan, Anju; Bhide, Pradeep G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Long, Jason E.; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA. [Crandall, James E.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM anju.vasudevan@mgh.harvard.edu; bhide@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NIDA NIH HHS [R01DA020796, R01 DA020796, R01 DA020796-03]; NINDS NIH HHS [P30 NS045776, P30 NS045776-05, P30NS045776, R01 NS043246, R01 NS043426, R01 NS043426-05, R01NS43246,] NR 49 TC 68 Z9 70 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2008 VL 11 IS 4 BP 429 EP 439 DI 10.1038/nn2074 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 279MM UT WOS:000254359300015 PM 18344991 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer SO NATURE REVIEWS CANCER LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; FACTOR RECEPTOR-2 BLOCKADE; PHASE-I; INTERSTITIAL HYPERTENSION; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; SOLID TUMORS; LIVER METASTASES AB The importance of multidisciplinary translational clinical trials is obvious; however, making them work is complex and challenging. Here I present an argument for designing and implementing multidisciplinary mechanistic trials and present the lessons our team at the Massachusetts General Hospital Cancer Center has learned from two such trials in cancer patients with locally advanced rectal carcinomas and recurrent glioblastomas. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumour Biol,Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumour Biol,Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 66 TC 110 Z9 116 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2008 VL 8 IS 4 BP 309 EP 316 DI 10.1038/nrc2346 PG 8 WC Oncology SC Oncology GA 276IC UT WOS:000254133500019 PM 18337733 ER PT J AU Lampe, E Yoshida, CFT De Oliveira, RV Lauer, GM Lewis-Ximenez, LL AF Lampe, Elisabeth Tachibana Yoshida, Clara Fumiko De Oliveira, Rosane Vieira Lauer, Georg M. Lewis-Ximenez, Lia Laura TI Molecular analysis and patterns of ALT and hepatitis C virus seroconversion in haemodialysis patients with acute hepatitis SO NEPHROLOGY LA English DT Article DE acute hepatitis; haemodialysis; hepatitis C virus; nosocomial transmission ID ALANINE AMINOTRANSFERASE; NOSOCOMIAL TRANSMISSION; INFECTION; HCV; UNIT; SURVEILLANCE; PREVALENCE; VIREMIA; SPREAD; BRAZIL AB Background: Haemodialysis (HD) continues to carry the risk of hepatitis C virus (HCV) transmission, with delayed seroconversion and often normal alanine aminotransferase (ALT) values increasing the likelihood of undetected infection and thus uninterrupted spread of HCV. The aim of this study was to identify the characteristic patterns of ALT changes and seroconversion during an outbreak of HCV in a HD unit. We also wanted to establish the relationship between infecting viruses using molecular analysis. Methods: All patients (n = 72) and staff (n = 23) of the HD unit were prospectively followed for 14 months. Serial measurements for ALT, HCV antibody and HCV-RNA were performed besides HCV sequence analysis. Results: The initial screening for anti-HCV and HCV-RNA confirmed chronic infection in 16/72 (22%) subjects and identified three subjects with recent seroconversion. In addition, five cases were reverse transcription-polymerase chain reaction positive alone for a total of eight recent cases. The interval between the initial observation of ALT changes and seroconversion varied from 1 to 8 months, and in several individuals ALT fluctuations only below the upper limit of normal were detected. However, relating each subject's ALT values to ALT at baseline, ALT levels increased between 1.6- and 4.7-fold. Molecular analysis provided evidence for transmission from two chronically infected source patients, probably because of inappropriate infection control measures. Conclusion: Our data highlight the importance of well-implemented safety precautions and regular HCV-RNA testing to prevent the further spread of HCV in this population, and suggest the use of ALT baseline values to identify infections that may remain unnoticed otherwise. C1 [Lampe, Elisabeth; Tachibana Yoshida, Clara Fumiko; De Oliveira, Rosane Vieira; Lewis-Ximenez, Lia Laura] Fiocruz MS, Inst Oswaldo Cruz, Lab Hepatitis Virais, BR-21040900 Rio De Janeiro, Brazil. [Lauer, Georg M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr & Infect Dis Div, Boston, MA 02114 USA. [Lauer, Georg M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lampe, E (reprint author), Fiocruz MS, Inst Oswaldo Cruz, Lab Hepatitis Virais, Avenida Brazil 4365, BR-21040900 Rio De Janeiro, Brazil. EM elampe@ioc.fiocruz.br FU NIAID NIH HHS [U19 AI066345] NR 24 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD APR PY 2008 VL 13 IS 3 BP 186 EP 192 DI 10.1111/j.1440-1797.2008.00931.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 282PA UT WOS:000254578500002 PM 18315700 ER PT J AU Schaeffner, ES Kurth, T Bowman, TS Gelber, RP Gaziano, JM AF Schaeffner, Elke S. Kurth, Tobias Bowman, Thomas S. Gelber, Rebecca P. Gaziano, J. Michael TI Blood pressure measures and risk of chronic kidney disease in men SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE blood pressure; creatinine clearance; hypertension; kidney disease; renal dysfunction ID STAGE RENAL-DISEASE; SERUM CREATININE; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; SYSTOLIC HYPERTENSION; NATIONAL-HEALTH; UNITED-STATES; MORTALITY; HEMODIALYSIS; PREDICTORS AB Background. High blood pressure (BP) has been associated with a decrease in kidney function. However, it remains unclear which BP measure best predicts impaired kidney function. Methods. We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) in predicting risk of chronic kidney disease (CKD). We prospectively followed 8093 male participants in the Physicians Health Study, without a known history of kidney disease at baseline, who provided BP values on the baseline and 24-month questionnaires, and for whom we had creatinine measures after 14 years of follow-up. Reported BP was averaged from both questionnaires. The main outcome was CKD, defined as an estimated glomerular filtration rate < 60 mLmin1.73 m(2). We used multivariable-adjusted logistic regression to evaluate the association between BP measures and CKD and compared models using the likelihood ratio test. Results. After 14 years of follow-up, 1039 men (12.8%) had CKD. An increase of 10 mmHg had corresponding multivariable-adjusted odds ratios (95% confidence intervals) of 1.11 (1.03-1.19) for SBP, 1.11 (1.00-1.23) for MAP, 1.14 (1.05-1.25) for PP and 1.05 (0.93-1.17) for DBP. SBP and PP were the strongest predictors of chronic kidney function, with equal predictive abilities. Combining BP measures did not add significantly to the prediction. Conclusions. Increases in SBP, PP and MAP were significantly associated with CKD. SBP may be the most clinically useful predictor of CKD, since no further calculations are required. C1 [Kurth, Tobias; Bowman, Thomas S.; Gelber, Rebecca P.; Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, Boston, MA 02120 USA. [Schaeffner, Elke S.] Charite Campus Virchow, Dept Med, Berlin, Germany. [Kurth, Tobias; Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02120 USA. [Kurth, Tobias] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bowman, Thomas S.; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Kurth, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [R01 CA097193]; NHLBI NIH HHS [HL 26490, HL 34595]; PHS HHS [34944] NR 28 TC 21 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2008 VL 23 IS 4 BP 1246 EP 1251 DI 10.1093/ndt/gfm757 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 281BW UT WOS:000254472400028 PM 17984108 ER PT J AU Lamborn, KR Yung, WKA Chang, SM Wen, PY Cloughesy, TF DeAngelis, LM Robins, HI Lieberman, FS Fine, HA Fink, KL Junck, L Abrey, L Gilbert, MR Mehta, M Kuhn, JG Aldape, KD Hibberts, J Peterson, PM Prados, MD AF Lamborn, Kathleen R. Yung, W. K. Alfred Chang, Susan M. Wen, Patrick Y. Cloughesy, Timothy F. DeAngelis, Lisa M. Robins, H. Ian Lieberman, Frank S. Fine, Howard A. Fink, Karen L. Junck, Larry Abrey, Lauren Gilbert, Mark R. Mehta, Minesh Kuhn, John G. Aldape, Kenneth D. Hibberts, Janelle Peterson, Pamela M. Prados, Michael D. CA N Amer Brain Tumor Consortium TI Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas SO NEURO-ONCOLOGY LA English DT Article DE brain tumors; clinical trial end points; glioma; progression-free survival ID PHASE-II; GLIOBLASTOMA-MULTIFORME; TRIALS AB The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials. C1 [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Yung, W. K. Alfred; Gilbert, Mark R.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX USA. [Hibberts, Janelle; Peterson, Pamela M.] Univ Texas MD Anderson Canc Ctr, Data Management Ctr, Houston, TX USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [DeAngelis, Lisa M.; Abrey, Lauren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robins, H. Ian; Mehta, Minesh] Univ Wisconsin Hosp, Madison, WI USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Div Neurooncol, Pittsburgh, PA USA. [Fine, Howard A.] Natl Canc Inst, Natl Inst Hlth, Neurooncol Branch, Bethesda, MD USA. [Fink, Karen L.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Junck, Larry] Univ Michigan Hosp, Dept Neurol, Ann Arbor, MI 48109 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. RP Lamborn, KR (reprint author), Univ Calif San Francisco, Dept Neurol Surg, UC Clin 808, San Francisco, CA 94143 USA. EM lambornk@neurosurg.ucsf.edu RI leng, xianwei/F-9073-2011; Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA 16672, CA 62399, CA 62412, CA 62422, CA 62426, CA 62455-08, P30 CA016672, U01 CA 62399 022030, U01 CA 62405, U01 CA 62407-08, U01 CA 62421-08, U01 CA062399, U01 CA062405, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01 CA062426]; NCRR NIH HHS [M01 RR 00042, M01 RR 00056, M01 RR 00079, M01 RR 00633, M01 RR 03186, M01 RR 0865, M01 RR000042, M01 RR000056, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186] NR 7 TC 223 Z9 228 U1 0 U2 4 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 APR PY 2008 VL 10 IS 2 BP 162 EP 170 DI 10.1215/15228517-2007-062 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 286NT UT WOS:000254853300007 PM 18356283 ER PT J AU Grossman, SA Olson, J Batchelor, T Peereboom, D Lesser, G Desideri, S Ye, XB Hammour, T Supko, JG AF Grossman, Stuart A. Olson, Jeffrey Batchelor, Tracy Peereboom, David Lesser, Glenn Desideri, Serena Ye, Xiaobu Hammour, Tarek Supko, Jeffrey G. CA New Approaches Brain Tumor The TI Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE celecoxib; COX-2 inhibitor; enzyme-inducing anticonvulsants; glioblastoma multiforme; pharmacology; radiation therapy; survival ID RECURRENT MALIGNANT GLIOMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PRIMARY HUMAN HEPATOCYTES; GROWTH-FACTOR RECEPTOR; PREGNANE-X-RECEPTOR; PROGNOSTIC-SIGNIFICANCE; CANCER PREVENTION; COX-2 INHIBITION; CYCLOOXYGENASE-2 INHIBITORS; ANTIEPILEPTIC DRUGS AB Cyclooxygenase-2 (COX-2) expression has been linked to the prognosis, angiogenesis, and radiation sensitivity of many malignancies. Celecoxib, a selective COX-2 inhibitor, is predominantly eliminated by hepatic metabolism. This study was conducted to determine the effects of hepatic enzyme-inducing antiseizure drugs (EIASDs) on the pharmacokinetics of celecoxib. The safety of celecoxib administered with radiation for glioblastoma and the effect of the combined treatment on survival were also evaluated. Patients were stratified based on concomitant use of EIASDs. Celecoxib (400) mg was administered orally twice a day until tumor progression or dose-limiting toxicity. Standard radiation was administered without adjuvant chemotherapy. Sampling was performed to define the plasma concentration/time profile for the initial dose of celecoxib and steady-state trough concentrations. Thirty-five patients (22 +EIASD, 13 -EIASD) were enrolled. There were no significant differences in age, performance status, extent of surgery, or Mini Mental State Exam scores between the two cohorts. The treatment was well tolerated. All patients in the +ElASD arm were taking phenytoin. There were no significant differences in any celecoxib pharmacokinetic parameters between 15 +EIASD and 12 -EIASD patients. With 31 of 35 patients deceased, estimated median survival time for all patients was 12 months (+EIASD, 11.5 months; -EIASD, 16 months; p = 0.11). The pharmacokinetics of celecoxib is not significantly affected by the concomitant administration of phenytoin. Celecoxib administered during and after radiation is well tolerated. The potential difference in survival between the +EIASD and -EIASD groups deserves further evaluation. C1 [Grossman, Stuart A.; Desideri, Serena; Ye, Xiaobu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Brain Canc Program, Baltimore, MD USA. [Olson, Jeffrey] Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA. [Batchelor, Tracy; Hammour, Tarek; Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol, Boston, MA USA. [Peereboom, David] Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. [Lesser, Glenn] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. RP Grossman, SA (reprint author), NABTT CNS Consortium, 1550 Orleans St,Room 1M-16, Baltimore, MD 21231 USA. EM grossman@jhmi.edu FU NCI NIH HHS [U01 CA105689, P30 CA 0516, U01 CA 62475, U01 CA062475, U01 CA 105689] NR 65 TC 9 Z9 9 U1 2 U2 2 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 APR PY 2008 VL 10 IS 2 BP 190 EP 198 DI 10.1215/15228517-2007-055 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 286NT UT WOS:000254853300010 PM 18287342 ER PT J AU Jarrett, SG Liang, LP Hellier, JL Staley, KJ Patel, M AF Jarrett, Stuart G. Liang, Li-Ping Hellier, Jennifer L. Staley, Kevin J. Patel, Manisha TI Mitochondrial DNA damage and impaired base excision repair during epileptogenesis SO NEUROBIOLOGY OF DISEASE LA English DT Article DE oxidative stress; mitochondrial dysfunction; status epilepticus; epileptogenesis; mtDNA damage; base excision repair ID SPONTANEOUS MOTOR SEIZURES; ALZHEIMERS-DISEASE BRAIN; TEMPORAL-LOBE EPILEPSY; ACID-INDUCED SEIZURES; OXIDATIVE STRESS; STATUS EPILEPTICUS; KAINIC ACID; HYDROGEN-PEROXIDE; POLYMERASE-GAMMA; EPITHELIAL-CELLS AB Oxidative stress and mitochondrial dysfunction are acute consequences of status epilepticus (SE). However, the role of mitochondrial oxidative stress and genomic instability during epileptogenesis remains unknown. Using the kainate animal model of temporal lobe epilepsy, we investigated oxidative mitochondrial DNA (mtDNA) damage and changes in the mitochondrial base excision repair pathway (mtBER) in the rat hippocampus for a period of 3 months after SE. Acute seizure activity caused a time-dependent increase in mitochondrial, but not nuclear 8-hydroxy-2-deoxyguanosine (8-OHdG/2dG) levels and a greater frequency of mtDNA lesions. This was accompanied by increased mitochondrial H2O2 production and a transient decrease in mtDNA repair capacity. The mtBER proteins 8-oxoguanine glycosylase (Ogg1) and DNA polymerase gamma (Pol gamma) demonstrated elevated expression at mRNA and protein levels shortly after SE and this was followed by a gradual improvement in mtDNA repair capacity. Recurrent seizures associated with the chronic phase of epilepsy coincided with the accumulation of mtDNA damage, increased mitochondrial H2O2 levels, decreased expression of Ogg1 and Poly and impaired mtDNA repair capacity. Together, increased oxidative mtDNA damage, mitochondrial H2O2 production and alterations in the mtBER pathway provide evidence for mitochondrial oxidative stress in epilepsy and suggest that mitochondrial injury may contribute to epileptogenesis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Jarrett, Stuart G.; Liang, Li-Ping; Patel, Manisha] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. [Hellier, Jennifer L.] Univ Colorado, Hlth Sci Ctr, Dept Cell & Dev Biol, Aurora, CO 80045 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Patel, M (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, 4200 E 9th Ave, Denver, CO 80262 USA. EM manisha.patel@uchsc.edu FU NINDS NIH HHS [R01 NS039587, R01NS39587, R01 NS039587-08] NR 63 TC 47 Z9 48 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2008 VL 30 IS 1 BP 130 EP 138 DI 10.1016/j.nbd.2007.12.009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 283VR UT WOS:000254665100014 PM 18295498 ER PT J AU Wehner, DT Haemaelaeinen, MS Mody, M Ahlfors, SP AF Wehner, Daniel T. Haemaelaeinen, Matti S. Mody, Maria Ahlfors, Seppo P. TI Head movements of children in MEG: Quantification, effects on source estimation, and compensation SO NEUROIMAGE LA English DT Article ID DIPOLE LOCALIZATION ACCURACY; SURFACE-BASED ANALYSIS; COORDINATE SYSTEM; MAGNETIC-FIELDS; HUMAN BRAIN; MODEL; MAGNETOENCEPHALOGRAPHY; RECONSTRUCTION; RESOLUTION; SHAPE AB Head movements during magnetuencephalography (MEG) recordings may lead to inaccurate localization of brain activity. This can be particularly problematic for studies with children. We quantified head movements in 8- to 12-year-old children performing a cognitive task and examined how the movements affected source estimation. Each child was presented auditory word stimuli in five 4-min runs. The mean change in the MEG sensor locations during the experiment ranged from 3 to 26mm across subjects. The variation in the head position was largest in the up-down direction. The mean localization error in equivalent current dipole (ECD) simulations was 12mm for runs with the most head movement, with the frontal cortex appearing to be most prone to errors due to head movements. In addition, we examined the effect of head movements on two types of source estimates, ECDs and minimum-norm estimates (MNE), for an auditory evoked response. Application of a recently introduced signal space separation (SSS) method to. compensate for the head movements was found to increase the goodness-of-fit of the ECDs, reduce the spatial confidence intervals of the ECDs, and enhance the peak amplitude in the MNE. These results are indicative of the SSS method being able to compensate for the spatial smoothing of the signals caused by head movements. Overall, the results suggest that MEG source estimates are relatively robust against head movements in children, and that confounds due to head movements can be successfully dealt with in MEG studies of developmental cognition. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MIT, MGH,HMS, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ahlfors, SP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Athinoula A Martinos Ctr, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM seppo@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-01A1, P41RR14075]; NIBIB NIH HHS [5T32EB001680, T32 EB001680, T32 EB001680-05]; NICHD NIH HHS [HD056355, R01 HD046171-03]; NIDCD NIH HHS [DC00038, DC00159, K23 DC000159, K23 DC000159-06, T32 DC000038, T32 DC000038-13] NR 33 TC 27 Z9 27 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2008 VL 40 IS 2 BP 541 EP 550 DI 10.1016/j.neuroimage.2007.12.026 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 283HQ UT WOS:000254627700016 PM 18252273 ER PT J AU van der Kouwe, AJW Benner, T Salat, DH Fischl, B AF van der Kouwe, Andre J. W. Benner, Thomas Salat, David H. Fischl, Bruce TI Brain morphometry with multiecho MPRAGE SO NEUROIMAGE LA English DT Article ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; GRAY-MATTER; MR-IMAGES; IN-VIVO; SEGMENTATION; SEQUENCE; ROBUST; OPTIMIZATION AB In brain morphometry studies using magnetic resonance imaging, several scans with a range of contrasts are often collected. The images may be locally distorted due to imperfect shimming in regions where magnetic susceptibility changes rapidly, and all scans may not be distorted in the same way. In multispectral studies it is critical that the edges of structures align precisely across all contrasts. The MPRAGE (NIPR) sequence has excellent contrast properties for cortical segmentation, while multiecho FLASH (MEF) provides better contrast for segmentation of subcortical structures. Here, a multiecho version of the MPRAGE (MEMPR) is evaluated using SIENA and FreeSurfer. The higher bandwidth of the MEMPR results in reduced distortions that match those of the MEF while the SNR is recovered by combining the echoes. Accurate automatic identification of cortex and thickness estimation is frustrated by the presence of dura adjacent to regions such as the entorhinal cortex. In the typical MPRAGE protocol, dura and cortex are approximately isointense. However, dura has substantially smaller T2* than cortex. This information is represented in the multiple echoes ofthe MEMPR. An algorithm is described for correcting cortical thickness using T2*. It is shown that with MEMPR, SIENA generates more reliable percentage brain volume changes and FreeSurfer generates more reliable cortical models. The regions where cortical thickness is affected by dura are shown. MEMPR did not substantially improve subcortical segmentations. Since acquisition time is the same for MEMPR as for MPRAGE, and it has better distortion properties and additional T2* information, MEMPR is recommended for morphometry studies. (C) 2007 Elsevier Inc. All rights reserved. C1 [van der Kouwe, Andre J. W.; Benner, Thomas; Salat, David H.; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Fischl, Bruce] MIT, AI Lab, Cambridge, MA 02139 USA. RP van der Kouwe, AJW (reprint author), Athinoula A Martinos Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM andre@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41-RR-14075, P41 RR014075, P41 RR014075-075751, P41 RR014075-075752, P41 RR014075-075753, P41 RR014075-086765, P41 RR014075-086766, P41 RR014075-086767, P41 RR014075-098601, P41 RR014075-098602, R01 RR016594, R01 RR016594-01A1, R01 RR016594-02, R01 RR016594-03, R01 RR016594-04, R01-RR16594-01A1, U24 RR021382, U24 RR021382-01, U24 RR021382-02, U24 RR021382-03, U24 RR021382-037970, U24 RR021382-037971, U24 RR021382-04, U24 RR021382-047975, U24 RR021382-047976, U24-RR021382]; NIBIB NIH HHS [R01 EB001550, R01 EB001550-01, R01 EB001550-02, R01 EB001550-03, R01 EB001550-04, R01 EB006758, R01 EB006758-01A1, R01-EB001550, R01-EB006758, R21 EB002530, R21 EB002530-01, R21 EB002530-02, R21-EB02530, U54 EB005149, U54 EB005149-01, U54 EB005149-010006, U54 EB005149-010019, U54 EB005149-02, U54 EB005149-020006, U54 EB005149-029001, U54 EB005149-03, U54 EB005149-030006, U54 EB005149-039001, U54 EB005149-04, U54 EB005149-040006, U54 EB005149-049001, U54 EB005149-04S1, U54-EB005149]; NINDS NIH HHS [R01 NS052585, R01 NS052585-01A1, R01 NS052585-02, R01 NS052585-02S1, R01 NS052585-03, R01-NS052585-01]; PHS HHS [BIRN002] NR 28 TC 159 Z9 159 U1 2 U2 11 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 APR 1 PY 2008 VL 40 IS 2 BP 559 EP 569 DI 10.1016/j.neuroimage.2007.12.025 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 283HQ UT WOS:000254627700018 PM 18242102 ER PT J AU Mehta, KM Yaffe, K Perez-Stable, EJ Stewart, A Barnes, D Kurland, BF Miller, BL AF Mehta, K. M. Yaffe, K. Perez-Stable, E. J. Stewart, A. Barnes, D. Kurland, B. F. Miller, B. L. TI Race/ethnic differences in AD survival in US Alzheimer's disease Centers SO NEUROLOGY LA English DT Article ID COORDINATING-CENTER; DEMENTIA; INDIVIDUALS; DIAGNOSIS; HEALTH; PREDICTORS; MORTALITY; AMERICAN; ONSET AB Objective: Survival after Alzheimer disease (AD) is poorly understood for patients of diverse race/ethnic groups. We examined whether nonwhite AD patients (African American, Latino, Asian, American Indian) had different rates of survival compared with white AD patients. Methods: The National Alzheimer's Coordinating Center (NACC) cataloged data from more than 30 Alzheimer's Disease Centers in the United States from 1984 to 2005. Patients aged 65 years or older with a diagnosis of possible/probable AD were included (n = 30,916). Survival was calculated using Cox proportional hazards models with a primary outcome of time to death. Secondary outcomes of this study were neuropathologic characteristics on an autopsied subsample (n = 3,017). Results: The 30,916 AD patients in the NACC were followed up for 2.4 (+/-) 2.9 years (mean age 77.6 +/- 6.5 years; 65% women; 19% nonwhite [12% African American, 4% Latino, 1.5% Asian, 0.5% American Indian, and 1% other]). Median survival was 4.8 years. African American and Latino AD patients had a lower adjusted hazard for mortality compared with white AD patients (African American hazard ratio [HR] 0.85,95% CI 0.74 to 0.96; Latino HR 0.57,95% CI 0.46 to 0.69). Asians and American Indians had similar adjusted hazards for mortality compared with white AD patients (p > 0.10 for both). African American and Latino autopsied AD patients had similar neuropathologic characteristics compared with white AD patients with similar clinical severity. Conclusions: African American and Latino Alzheimer disease (AD) patients may have longer survival compared with white AD patients. Neuropathology findings did not explain survival differences by race. Determining the underlying factors behind survival differences may lead to longer survival for AD patients of all race/ethnic backgrounds. C1 [Mehta, K. M.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Yaffe, K.; Barnes, D.; Miller, B. L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, K.; Miller, B. L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Perez-Stable, E. J.] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94121 USA. [Stewart, A.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94121 USA. [Mehta, K. M.; Perez-Stable, E. J.; Stewart, A.] Univ Calif San Francisco, Med Effectiveness Res Ctr Diverse Populat, San Francisco, CA 94121 USA. [Kurland, B. F.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Mehta, K. M.; Yaffe, K.; Barnes, D.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Mehta, KM (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM kala.mehta@ucsf.edu OI Kurland, Brenda/0000-0002-5669-0595 FU NIA NIH HHS [U01AG016976, K-01AG025444-01A1, K01 AG025444, K01 AG025444-01A1, P30 AG 15272, P30 AG015272, P50 AG023501, P50-AG023501, U01 AG016976] NR 25 TC 34 Z9 34 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 1 PY 2008 VL 70 IS 14 BP 1163 EP 1170 DI 10.1212/01.wnl.0000285287.99923.3c PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 282OH UT WOS:000254576600003 PM 18003939 ER PT J AU Landers, JE Leclerc, AL Shi, L Virkud, A Cho, T Maxwell, MM Henry, AF Polak, M Glass, JD Kwiatkowski, TJ Al-Chalabi, A Shaw, CE Leigh, PN Rodriguez-Leyza, I McKenna-Yasek, D Sapp, PC Brown, RH AF Landers, J. E. Leclerc, A. L. Shi, L. Virkud, A. Cho, T. Maxwell, M. M. Henry, A. F. Polak, M. Glass, J. D. Kwiatkowski, T. J. Al-Chalabi, A. Shaw, C. E. Leigh, P. N. Rodriguez-Leyza, I. McKenna-Yasek, D. Sapp, P. C. Brown, R. H., Jr. TI New VAPB deletion variant and exclusion of VAPB mutations in familial ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; GENE-MUTATIONS; PROTEIN; POPULATION; DATABASE; FORM AB Objective: Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder involving upper and lower motor neurons. The vesicle-associated membrane protein B (VAPB) gene has been genetically linked to ALS in several large Brazilian families in which the disorder is caused by a proline to serine mutation at codon 56 (P56S). No additional mutations have been identified. Methods: To establish the prevalence of VAPB mutations, we screened 80 familial ALS samples by DNA sequencing. Results: Our study failed to identify any novel VAPB gene mutations but identified a single Brazilian family harboring the P56S mutation. In a second familial ALS case, we identified a three-base pair deletion within exon 5 of the VAPB gene that deleted the serine residue at position 160 (Delta S160). This variant is detected in a normal population at low frequency (0.45%). Analyses of homology alignment and secondary structure predict that this deletion significantly alters the structure of VAPB, although a GFP-Delta S160 VAPB fusion protein demonstrates a wild-type subcellular localization. This contrasts the aberrant localization observed in a GFP-P56S VAPB fusion protein. The allele frequency of Delta S160 in patients with sporadic ALS does not differ significantly from that in the normal population. Conclusions: Mutations in the VAPB gene are rare and the Delta S160 variant does not contribute to the development of amyotrophic lateral sclerosis. C1 [Landers, J. E.; Leclerc, A. L.; Shi, L.; Virkud, A.; Maxwell, M. M.; Henry, A. F.; Kwiatkowski, T. J.; Rodriguez-Leyza, I.; McKenna-Yasek, D.; Sapp, P. C.; Brown, R. H., Jr.] Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. [Polak, M.; Glass, J. D.] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA USA. [Al-Chalabi, A.; Shaw, C. E.; Leigh, P. N.] Kings Coll London, Dept Neurol, Inst Psychiat, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England. [Rodriguez-Leyza, I.] Colonia Univ, Cent Hosp, Dept Neurol, San Luis Potosi, Mexico. [Sapp, P. C.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Landers, JE (reprint author), Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Room 3216,Bldg 149,13th St, Charlestown, MA 02129 USA. EM jelanders@partners.org RI Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 FU Howard Hughes Medical Institute; Medical Research Council [, G0500289]; NINDS NIH HHS [F32NS048809] NR 30 TC 32 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 1 PY 2008 VL 70 IS 14 BP 1179 EP 1185 DI 10.1212/01.wnl.0000289760.85237.4e PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 282OH UT WOS:000254576600005 PM 18322265 ER PT J AU Hashimoto, JG Wiren, KM AF Hashimoto, Joel G. Wiren, Kristine M. TI Neurotoxic consequences of chronic alcohol withdrawal: Expression profiling reveals importance of gender over withdrawal severity SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; microarray; neurotoxicity; animal model ID NEUROENDOCRINE-SPECIFIC PROTEIN; ETHANOL-REGULATED GENE; MICROARRAY ANALYSIS; SEX-DIFFERENCES; RESISTANT MICE; BRAIN VOLUMES; SEIZURE-PRONE; SENSITIVITY; SUSCEPTIBILITY; CONSUMPTION AB While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways were more altered by alcohol. Examination of ethanol-regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse. C1 [Hashimoto, Joel G.; Wiren, Kristine M.] OHSU, Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Hashimoto, Joel G.; Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Wiren, KM (reprint author), OHSU, Portland VA Med Ctr, Res Serv, P3 R&D39, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU NIAAA NIH HHS [P60 AA010760, AA-13783, R01 AA013194, R01 AA013194-03] NR 75 TC 34 Z9 35 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2008 VL 33 IS 5 BP 1084 EP 1096 DI 10.1038/sj.npp.1301494 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 273UQ UT WOS:000253957600013 PM 17593928 ER PT J AU Nogueira, RG Schwamm, LH Buonanno, FS Koroshetz, WJ Yoo, AJ Rabinov, JD Pryor, JC Hirsch, JA AF Nogueira, Raul G. Schwamm, Lee H. Buonanno, Ferdinando S. Koroshetz, Walter J. Yoo, Albert J. Rabinov, James D. Pryor, Johnny C. Hirsch, Joshua A. TI Low-pressure balloon angioplasty with adjuvant pharmacological therapy in patients with acute ischemic stroke caused by intracranial arterial occlusions SO NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 3rd Annual Course and Workshop of the American-Society-of-Interventional-and-Therapeutic-Neuroradiology CY AUG, 2006 CL Rio Grande, PR SP Amer Soc Intervent & Therapeut Neuroradiol DE balloon angioplasty; stroke; eptifibatide ID TISSUE-PLASMINOGEN ACTIVATOR; INTRAARTERIAL THROMBOLYSIS; INTRACEREBRAL HEMORRHAGE; MERCI TRIAL; RECANALIZATION; SAFETY; REPERFUSION; INFARCTION; EFFICACY AB Introduction The use of coronary balloons in the cerebral vasculature is limited due to their poor trackability and increased risk of vessel injury. We report our experience using more compliant elastomer balloons for thrombus resistant to intraarterial (IA) pharmacological and mechanical thrombolysis in acute stroke. Methods We retrospectively analyzed 12 consecutive patients with an occluded intracranial artery treated with angioplasty using a low-pressure elastomer balloon. Angiograms were graded according to the Thrombolysis in Cerebral Infarction (TICI) and Qureshi grading systems. Outcomes were categorized as independent (modified Rankin scale, mRS, score <= 2), dependent (mRS score 3-5), or dead (mRS score 6). Results Included in the study were 12 patients (mean age 66 +/- 17 years, range 31-88 years; mean baseline National Institutes of Health stroke scale score 17 +/- 3, range 12-23). The occlusion sites were: internal carotid artery (ICA) terminus (five patients, including two concomitant cervical ICA occlusions), M1 segment (two patients), and basilar artery (two patients). Pharmacological treatment included intravenous (IV) t-PA only (two patients), IA urokinase only (nine patients), both IV t-PA and IA urokinase (one patient), and IV and/or IA eptifibatide (eight patients). Mean time to treatment was 5.9 +/- 3.9 h (anterior circulation) and 11.0 +/- 7.2 h (posterior circulation). Overall recanalization rate (TICI grade 2/3) was 91.6%. Procedure-related morbidity occurred in one patient (distal posterior inferior cerebellar artery embolus). There were no symptomatic hemorrhages. Outcomes at 90 days were independent (five patients), dependent (three patients) and dead (four patients, all due to progression of stroke with withdrawal of care). Conclusion Angioplasty of acutely occluded intracranial arteries with low-pressure elastomer balloons results in high recanalization rates with an acceptable degree of safety. Prior use of thrombolytics may increase the chances of recanalization, and glycoprotein IIb-IIIa inhibitors may be helpful in preventing reocclusion and in increasing patency rates. C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nogueira, Raul G.; Yoo, Albert J.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol,Massachusetts Gen Hosp, Endovasc Neurosurg Intervent Neuroradiol Sect, Boston, MA 02115 USA. [Nogueira, Raul G.; Yoo, Albert J.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurosurg, Endovasc Neurosurg Intervent Neuroradiol Sect, Boston, MA 02115 USA. [Nogueira, Raul G.; Schwamm, Lee H.; Buonanno, Ferdinando S.; Koroshetz, Walter J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Neurocrit Care & Vasc Neurol Sect, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Blake 12 Room 1291,55 Fruit St, Boston, MA 02114 USA. EM rnogueira@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 24 TC 26 Z9 28 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD APR PY 2008 VL 50 IS 4 BP 331 EP 340 DI 10.1007/s00234-007-0340-z PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 280DM UT WOS:000254405100006 PM 18172631 ER PT J AU Hersch, SM Rosas, HD AF Hersch, Steven M. Rosas, H. Diana TI Neuroprotection for Huntington's disease: Ready, set, slow SO NEUROTHERAPEUTICS LA English DT Review DE huntington's disease; neuroprotection; disease modification; neurogenetics; genetic testing; clinical trials; presymptomatic; premanifest ID TRANSGENIC MOUSE MODELS; NEURONAL INTRANUCLEAR INCLUSIONS; HISTONE DEACETYLASE INHIBITORS; CREB-BINDING PROTEIN; MUTANT HUNTINGTIN; NEUROTROPHIC FACTOR; MUTATION CARRIERS; CONTROLLED TRIAL; REDUCE TOXICITY; COENZYME Q(10) AB The ultimate goal for Huntington's disease (HD) therapeutics is to develop disease-modifying neuroprotective therapies that can delay or prevent illness in those who are at genetic risk and can slow progression in those who are affected clinically. Neuroprotection is the preservation of neuronal structure, function, and viability, and neuroprotective therapy is thus targeted at the underlying pathology of HD. rather than at its specific symptoms. Preclinical target discovery research in HD is identifying numerous distinct targets, along with options for modulating them, with some proceeding into large-scale efficacy studies in early symptomatic HD subjects. The first pilot studies of neuroprotective compounds in premanifest HD are also soon to begin. This review discusses the opportunities for neuroprotection in HD, clinical methodology in premanifest and manifest HD, the clinical assessment of neuroprotection, molecular targets and therapeutic leads, and the current state of clinical development. C1 [Hersch, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Rosas, H. Diana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neuroimaging Aging & Neurodegenerat Dis, Boston, MA 02129 USA. RP Hersch, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis, MGH E,Bldg 114,Room 2005,114 16th St, Boston, MA 02129 USA. EM hersch@helix.mgh.harvard.edu FU FDA HHS [R01FD003359]; NCCIH NIH HHS [R01AT000613, U01 AT000613, U01 AT000613-06A1, U01AT000613]; NHGRI NIH HHS [R01HG002449]; NINDS NIH HHS [P01NS045242, P01 NS045242, P01 NS045242-01, P01NS058793, R01NS04286, U01NS045806] NR 137 TC 25 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2008 VL 5 IS 2 BP 226 EP 236 DI 10.1016/j.nurt.2008.01.003 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 288SC UT WOS:000255005100006 PM 18394565 ER PT J AU Peterson, AL Nutt, JG AF Peterson, Amie L. Nutt, John G. TI Treatment of Parkinson's disease with trophic factors SO NEUROTHERAPEUTICS LA English DT Review DE Parkinson's disease; trophic factors; clinical trials; glial-derived neurotrophic factors; neurturin ID BLOOD-BRAIN-BARRIER; NERVE GROWTH-FACTOR; NIGROSTRIATAL DOPAMINERGIC SYSTEM; NEUROTROPHIC FACTOR EXPRESSION; N-TERMINAL TRIPEPTIDE; PARTIAL LESION MODEL; SUBSTANTIA-NIGRA; IN-VIVO; INTRAPUTAMENAL INFUSION; RHESUS-MONKEYS AB Trophic factors are proteins that support and protect subpopulations of cells. A number have been reported to act on dopaminergic neurons in vitro and in vivo, making them potential therapeutic candidates for Parkinson's disease. All of these candidate factors protect dopaminergic neurons if given prior to, or with, selective neurotoxins. Fewer trophic factors, primarily glial-derived neurotrophic factor (GDNF) and its relative, neurturin (NRTN; also known as NTN), have been shown to restore function in damaged dopamine neurons after the acute effects of neurotoxins have subsided. A major barrier to clinical translation has been delivery. GDNF delivered by intracerebroventricular injection in patients was ineffective, probably because GDNF did not reach the target, the putamen, and intraputaminal infusion was ineffective, probably because of limited distribution within the putamen. A randomized clinical trial with gene therapy for NRTN is underway, in an attempt to overcome these problems with targeting and distribution. Other strategies are available to induce trophic effects in the CNS, but have not yet been the focus of human research. To date, clinical trials have focused on restoration of function (i.e., improvement of parkinsonism). Protection (i.e., slowing or halting disease progression and functional decline) might be a more robust effect of trophic agents. Laboratory research points to their effectiveness in protecting, neurons and even restoring dopaminergic function after a monophasic neurotoxic insult. Utility for such compounds in patients with Parkinson's disease and ongoing loss of dopaminergic neurons remains to be proven. C1 [Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Portland VA Med Ctr, PADRECC, Portland, OR 97239 USA. RP Nutt, JG (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM nuttj@ohsu.edu FU NINDS NIH HHS [R01-NS21062] NR 104 TC 104 Z9 110 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2008 VL 5 IS 2 BP 270 EP 280 DI 10.1016/j.nurt.2008.02.003 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 288SC UT WOS:000255005100010 PM 18394569 ER PT J AU Gregor, KL Zvolensky, MJ McLeish, AC Bernstein, A Morissette, S AF Gregor, Kristin L. Zvolensky, Michael J. McLeish, Alison C. Bernstein, Amit Morissette, Sandra TI Anxiety sensitivity and perceived control over anxiety-related events: Associations with smoking outcome expectancies and perceived cessation barriers among daily smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; IDENTIFICATION TEST AUDIT; NICOTINE DEPENDENCE; INCREMENTAL VALIDITY; NEGATIVE AFFECT; PANIC DISORDER; SUBSTANCE USE; ALCOHOL; CONSUMPTION; PREDICTORS AB The present investigation examined the extent to which the cognitive factors of anxiety sensitivity (AS) and perceived control over anxiety-related events are independently related to smoking outcome expectancies and perceived barriers to quitting. Participants were 125 community-recruited adult, daily smokers. Consistent with hypotheses, AS and perceived control over anxiety-related events independently and significantly predicted smokers' expectancies for negative affect reduction from smoking, whereas only AS predicted expectancies for negative personal consequences from smoking. Also as hypothesized, AS and perceived control over anxiety-related events each independently and significantly predicted level of general perceived barriers to quitting smoking. All of the observed significant effects were evident above and beyond the variance accounted for by gender, alcohol consumption, number of cigarettes smoked per day, and negative affectivity. Together, these findings further the literature on the relation between anxiety-relevant cognitive factors and psychological smoking processes. C1 [Gregor, Kristin L.; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [McLeish, Alison C.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Bernstein, Amit] Palo Alto VA Syst, Palo Alto, CA USA. [Morissette, Sandra] Boston Univ, Sch Med, Boston, MA 02118 USA. [Morissette, Sandra] VA Boston Healthcare Syst, Boston, MA USA. RP Zvolensky, MJ (reprint author), Univ Vermont, Dept Psychol, 2 Colchester Ave,John Dewey Hall, Burlington, VT 05405 USA. EM michael.zvolensky@uvm.edu FU NIDA NIH HHS [1 R01 DA018734-01A1, 1 R21 DA016227, R03 DA16307-01] NR 47 TC 30 Z9 31 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2008 VL 10 IS 4 BP 627 EP 635 DI 10.1080/14622200801978706 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 294OY UT WOS:000255416600008 PM 18418785 ER PT J AU Demichelis, F Greulich, H Macoska, JA Beroukhim, R Sellers, WR Garraway, L Rubin, MA AF Demichelis, Francesca Greulich, Heidi Macoska, Jill A. Beroukhim, Rameen Sellers, William R. Garraway, Levi Rubin, Mark A. TI SNP panel identification assay (SPIA): a genetic-based assay for the identification of cell lines SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CANCER; CARCINOMA; BREAST; DELETIONS; SELECTION; ANCESTRY; MARKERS AB Translational research hinges on the ability to make observations in model systems and to implement those findings into clinical applications, such as the development of diagnostic tools or targeted therapeutics. Tumor cell lines are commonly used to model carcinogenesis. The same tumor cell line can be simultaneously studied in multiple research laboratories throughout the world, theoretically generating results that are directly comparable. One important assumption in this paradigm is that researchers are working with the same cells. However, recent work using high throughput genomic analyses questions the accuracy of this assumption. Observations by our group and others suggest that experiments reported in the scientific literature may contain pre-analytic errors due to inaccurate identities of the cell lines employed. To address this problem, we developed a simple approach that enables an accurate determination of cell line identity by genotyping 34 single nucleotide polymorphisms (SNPs). Here, we describe the empirical development of a SNP panel identification assay (SPIA) compatible with routine use in the laboratory setting to ensure the identity of tumor cell lines and human tumor samples throughout the course of long term research use. C1 [Demichelis, Francesca; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Demichelis, Francesca; Greulich, Heidi; Beroukhim, Rameen; Sellers, William R.; Garraway, Levi; Rubin, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. [Greulich, Heidi; Beroukhim, Rameen; Sellers, William R.; Garraway, Levi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Greulich, Heidi; Beroukhim, Rameen; Sellers, William R.; Garraway, Levi] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Greulich, Heidi; Beroukhim, Rameen; Sellers, William R.; Garraway, Levi; Rubin, Mark A.] Broad Inst Harvard, Cambridge, MA 02138 USA. [Greulich, Heidi; Beroukhim, Rameen; Sellers, William R.; Garraway, Levi; Rubin, Mark A.] MIT, Cambridge, MA 02139 USA. [Macoska, Jill A.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Macoska, Jill A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Demichelis, F (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM frd2004@med.cornell.edu OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [K08 CA122833, K08 CA122833-01A1, P50 CA069568, P50 CA090381, P50 CA097186, P50 CA69568, R01 CA109038, R01CA109038]; NIA NIH HHS [R01AG21404, R01 AG021404] NR 31 TC 25 Z9 25 U1 0 U2 3 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 APR PY 2008 VL 36 IS 7 BP 2446 EP 2456 DI 10.1093/nar/gkn089 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290VZ UT WOS:000255152200037 PM 18304946 ER PT J AU Shiften, JL Clayton, AH Monz, B Russo, P Beinett, L Johannes, CB AF Shiften, Jan L. Clayton, Anita H. Monz, Brigitta Russo, Patricia Beinett, Lee Johannes, Catherine B. TI Treatment-seeking behavior of US women with hypoactive sexual desire disorder SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 56th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 03-07, 2008 CL New Orleans, LA SP Amer Coll Obstetricians & Gynecologists C1 [Shiften, Jan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2008 VL 111 IS 4 SU S BP 17S EP 17S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 280NT UT WOS:000254434200040 ER PT J AU Subak, LL Brubaker, L Chai, TC Creasman, JM Diokno, AC Goode, PS Kraus, SR Kusek, JW Leng, WW Lukacz, ES Norton, P Tennstedt, S AF Subak, Leslee L. Brubaker, Linda Chai, Toby C. Creasman, Jennifer M. Diokno, Ananias C. Goode, Patricia S. Kraus, Stephen R. Kusek, John W. Leng, Wendy W. Lukacz, Emily S. Norton, Peggy Tennstedt, Sharon CA Urinary Incontinence Treatment Ne TI High costs of urinary incontinence among women electing surgery to treat stress incontinence SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID WILLINGNESS-TO-PAY; QUALITY-OF-LIFE; COMMUNITY; IMPACT; INSTRUMENT; DISEASE AB OBJECTIVE: To estimate costs for incontinence management, health-related quality of life, and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence. METHODS: A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial, a randomized surgical trial. Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of resources used (supplies, laundry, dry cleaning) by national resource costs ($2006). Health-related quality of life was estimated with the Health Utilities Index Mark 3. Participants estimated willingness to pay for 100% improvement in incontinence. Potential predictors of these outcomes were examined by using multivariable linear regression. RESULTS: Mean age was 52 +/- 10 years, and mean number of weekly incontinence episodes was 22 +/- 21. Mean and median (25%, 75% interquartile range) estimated personal costs for incontinence management among all women were $14 +/- $24 and $8 (interquartile range $3, $18) per week, and 617 (94%) women reported any cost. Costs increased significantly with incontinence frequency and mixed compared with stress incontinence. The mean and median Health Utilities Index Mark 3 scores were 0.73 +/- 0.25 and 0.84 (interquartile range 0.63, 0.92). Women were willing to pay a mean of $118 +/- $132 per month for complete resolution of incontinence, and willingness to pay increased significantly with greater expected incontinence improvement, household income, and incontinent episode frequency. CONCLUSION: Urinary incontinence is associated with substantial costs. Women spent nearly $750 per year out of pocket for incontinence management, had a significant decrement in quality of life, and were willing to pay nearly $1,400 per year for cure. C1 [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Loyola Univ, Dept Obstet Gynecol & Reprod Sci, Chicago, IL 60611 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Alabama, Birmingham, AL USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] NIDDK, Bethesda, MD USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Pittsburgh, Dept Urol, Pittsburgh, PA USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Subak, Leslee L.; Brubaker, Linda; Chai, Toby C.; Creasman, Jennifer M.; Diokno, Ananias C.; Goode, Patricia S.; Kraus, Stephen R.; Kusek, John W.; Leng, Wendy W.; Lukacz, Emily S.; Norton, Peggy; Tennstedt, Sharon] New England Res Inst, Watertown, MA 02172 USA. RP Subak, LL (reprint author), UCSF, Mt Zions Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM subakl@obgyn.ucsf.edu FU NIDDK NIH HHS [U01 DK058225, U01 DK058229, U01 DK058234, U01 DK58225, U01 DK58229, U01 DK58234, U01 DK60380, U01 DK058231, U01 DK060379, U01 DK060379-05, U01 DK060380, U01 DK060393, U01 DK060395, U01 DK060397, U01 DK060401, U01 DK58231, U01 DK60379, U01 DK60393, U01 DK60395, U01 DK60397]; PHS HHS [60401] NR 34 TC 36 Z9 37 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2008 VL 111 IS 4 BP 899 EP 907 DI 10.1097/AOG.0b013e31816a1e12 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 280NO UT WOS:000254433700013 PM 18378749 ER PT J AU Jarvholm, B From, C Lewold, S Malchau, H Vingard, E AF Jarvholm, B. From, C. Lewold, S. Malchau, H. Vingard, E. TI Incidence of surgically treated osteoarthritis in the hip and knee in male construction workers SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID RISK-FACTORS; OCCUPATIONAL ACTIVITIES; FLOOR LAYERS; COHORT; DISORDERS; UPDATE; CARPET; WOMEN; MEN AB Objective: Occupational workload has been associated with an increased risk of osteoarthritis. The objective was to further examine the association between workload and occurrence of osteoarthritis and in particular to study whether heavy workload has similar importance as a causative factor for osteoarthritis of the hip and knee. Methods: In a cohort study, the authors investigated the incidence of surgically treated osteoarthritis in the hip and knee among men employed in the Swedish construction industry (n = 204 741). Incident cases were found by linkage with the Swedish hospital discharge register between 1987 and 1998. Incidence rates adjusted for age and BMI were compared between different occupational groups. Results: The incidence rates for osteoarthritis in hip and knee were positively correlated (r = 0.62; p = 0.01). There was a significantly increased risk of surgically treated osteoarthritis in the knee among floor layers, asphalt workers, sheet-metal workers, rock workers, plumbers, brick layers, wood workers and concrete workers. Even if there was a trend towards increased relative risks for osteoarthritis in the hip in floor layers, asphalt workers, wood workers and concrete workers they were not statistically significant. The relative risk for surgically treated osteoarthritis of the knee was 4.7 (95% CI 1.8 to 12.3) among floor layers, indicating an attributable fraction for work factors of 79%. Conclusions: This study shows that some work-related factors seem to be risk factors for osteoarthritis both in the knee and hip. However, the risk factors seem to be of greater importance for osteoarthritis in the knee compared with the hip. This study indicates that at least 50% of the cases of severe osteoarthritis of the knee can be prevented through decreasing occupational risk factors in some occupational groups. C1 [Jarvholm, B.; From, C.] Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. [Lewold, S.] Lund Univ, Dept Orthoped, Lund, Sweden. [Malchau, H.] Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. [Vingard, E.] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. RP Jarvholm, B (reprint author), Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. EM Bengt.jarvholm@envmed.umu.se NR 24 TC 31 Z9 31 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD APR PY 2008 VL 65 IS 4 BP 275 EP 278 DI 10.1136/oem.2007.033365 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 276DH UT WOS:000254121000012 PM 17928390 ER PT J AU Pasquale, LR Dolgitser, M Wentzloff, JN Stern, LS Doyle, JJ Chiang, TH Walt, JG AF Pasquale, Louis R. Dolgitser, Margarita Wentzloff, Jeffrey N. Stern, Lee S. Doyle, John J. Chiang, Tina H. Walt, John G. TI Health care charges for patients with ocular hypertension or primary open-angle glaucoma SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 04, 2006 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID COST-EFFECTIVENESS; RESOURCE UTILIZATION; MEDICATIONS; BIMATOPROST; MANAGEMENT; LATANOPROST; DISEASE; STAGE; RISK AB Objectives: To determine the total and condition-related direct health care charges of patients with ocular hypertension (OH) or primary open-angle glaucoma (POAG) and identify factors that affect these charges. Design: Retrospective cohort study. Participants: Patients with OH (n = 36 767) and POAG (n = 72 412) with >= 1 year of continuous enrollment during calendar years 1998 through 2005 in a nationally representative, multimanaged health plan database (PharMetrics). Methods: First year total health care and condition-related charges were calculated. Subsequently multivariate linear regression models determined the impact of ophthalmic condition (OH or POAG), age, index year, gender, geographic region, payer mix, product type, treatment with glaucoma medication, ocular comorbidities, and systemic comorbidities on these charges. Main Outcome Measures: Per-person per year first-year total health care and ocular condition-related charges in United States dollars, adjusted for multiple covariates. Results: Patients with POAG had significantly higher adjusted total and condition-related health care charges during the first year of follow-up than patients with OH in multivariable analysis ($2070 vs. $1990, P < 0.0001 and $556 vs. $322 P < 0.0001, respectively). Females and older patients had higher total health care charges compared with males and younger patients ($586 or 28.3% more; P < 0.0001 and $27 per year or 0.8% per year more; P < 0.0001, respectively). However, neither gender nor age were strong determinants of condition-related charges (P = 0.13 and P = 0.052, respectively). Index year, region, payer, and product types significantly dictated both total and disease-related charges. Patients with ocular comorbid conditions, including cataracts, cataract surgery, diabetic retinopathy, and blindness, had significantly higher total and condition-related health care charges than patients without these conditions (P < 0.0001). Conclusion: Total and condition-related health care charges are considerable for patients with OH and POAG. These data identify several factors that dictate these charges. C1 [Dolgitser, Margarita; Stern, Lee S.] Analyt Int, New York, NY 10016 USA. [Pasquale, Louis R.; Wentzloff, Jeffrey N.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Doyle, John J.; Chiang, Tina H.; Walt, John G.] Allergan Pharmaceut Inc, Irvine, CA USA. RP Stern, LS (reprint author), Analyt Int, 450 Pk Ave S,12th Floor, New York, NY 10016 USA. EM lstern@analyticaintl.com NR 31 TC 7 Z9 7 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 APR PY 2008 VL 115 IS 4 BP 633 EP 638 DI 10.1016/j.ophtha.2007.04.059 PG 6 WC Ophthalmology SC Ophthalmology GA 281CU UT WOS:000254475100007 PM 17716736 ER PT J AU Faveri, M Mayer, MPA Feres, M de Figueiredo, LC Dewhirst, FE Paster, BJ AF Faveri, M. Mayer, M. P. A. Feres, M. de Figueiredo, L. C. Dewhirst, F. E. Paster, B. J. TI Microbiological diversity of generalized aggressive periodontitis by 16S rRNA clonal analysis SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE aggressive periodontitis; subgingival microbiota; uncultivable bacteria; 16S ribosomal identification ID EARLY-ONSET PERIODONTITIS; RAPIDLY PROGRESSIVE PERIODONTITIS; POLYMERASE-CHAIN-REACTION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; SUBGINGIVAL PLAQUE; PERIODONTOPATHIC BACTERIA; YOUNG-ADULTS; BACTEROIDES-INTERMEDIUS; JUVENILE PERIODONTITIS; CLINICAL-PARAMETERS AB Background/aim: The purpose of this study was to determine the bacterial diversity in the subgingival plaque of subjects with generalized aggressive periodontitis by using culture-independent molecular methods based on 16S ribosomal DNA cloning. Methods: Samples from 10 subjects with generalized aggressive periodontitis were selected. DNA was extracted and the 16S rRNA gene was amplified with the universal primer pairs 9F and 1525R. Amplified genes were cloned, sequenced, and identified by comparison with known 16S rRNA sequences. Results: One hundred and ten species were identified from 10 subjects and 1007 clones were sequenced. Of these, 70 species were most prevalent. Fifty-seven percent of the clone (40 taxa) sequences represented phylotypes for which no cultivated isolates have been reported. Several species of Selenomonas and Streptococcus were found at high prevalence and proportion in all subjects. Overall, 50% of the clone libraries were formed by these two genera. Selenomonas sputigena, the species most commonly detected, was found in nine of 10 subjects. Other species of Selenomonas were often present at high levels, including S. noxia, Selenomonas sp. EW084, Selenomonas sp. EW076, Selenomonas FT050, Selenomonas sp. P2PA_80, and Selenomonas sp. strain GAA14. The classical putative periodontal pathogens, such as, Aggregatibacter actinomycetemcomitans, was below the limit of detection and was not detected. Conclusion: These data suggest that other species, notably species of Selenomonas, may be associated with disease in generalized aggressive periodontitis subjects. C1 [Faveri, M.; Mayer, M. P. A.] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo, Brazil. [Faveri, M.; Mayer, M. P. A.; Feres, M.] Univ Guarulhos, Dent Res Div, Dept Periodontol, Guarulhos, SP, Brazil. [Dewhirst, F. E.; Paster, B. J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Mayer, MPA (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Av Lineu Prestes 1374, BR-05508900 Sao Paulo, Brazil. EM mpamayer@icb.usp.br RI Faveri, Marcelo/C-4738-2012; Mayer, Marcia/D-4645-2012; Feres, Magda/H-7964-2012 OI Mayer, Marcia/0000-0002-5910-8433; NR 57 TC 71 Z9 77 U1 0 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2008 VL 23 IS 2 BP 112 EP 118 DI 10.1111/j.1399-302X.2007.00397.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 262KY UT WOS:000253148600004 PM 18279178 ER PT J AU Haffajee, AD Patel, M Socransky, SS AF Haffajee, A. D. Patel, M. Socransky, S. S. TI Microbiological changes associated with four different periodontal therapies for the treatment of chronic periodontitis SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE antibiotics; antibiotic resistance; azithromycin; chronic periodontitis; metronidazole; periodontal pathogens; periodontal therapy; scaling and root planing; sub-antimicrobial dose doxycycline ID MUCOID PSEUDOMONAS-AERUGINOSA; DNA-DNA HYBRIDIZATION; ANTIBIOTIC-RESISTANCE; CLINICAL-PARAMETERS; METRONIDAZOLE; AZITHROMYCIN; AMOXICILLIN; DOXYCYCLINE; INFECTIONS; DISEASES AB Background/aims: To examine subgingival microbiological changes in chronic periodontitis subjects receiving scaling and root planing (SRP) alone or with systemically administered azithromycin, metronidazole or a sub-antimicrobial dose of doxycycline. Methods: Ninety-two periodontitis subjects were randomly assigned to receive SRP alone or combined with azithromycin, metronidazole or sub-antimicrobial dose doxycycline. Subgingival plaque samples taken at baseline, 2 weeks, and 3, 6, and 12 months were analyzed for 40 bacterial species using checkerboard DNA-DNA hybridization. Percentage of resistant species and percentage of sites harboring species resistant to the test antibiotics were determined at each time-point. Results: All treatments reduced counts of red complex species at 12 months, although no significant differences were detected among treatment groups for most species at all time-points. Both antibiotics significantly reduced counts of red complex species by 2 weeks. Percentage of resistant isolates increased in plaque samples in all adjunctive treatment groups, peaking at the end of administration, but returned to pretreatment levels by 12 months. Conclusion: The significant reduction of red and orange complex species at 2 weeks in the subjects receiving SRP plus azithromycin or metronidazole may have contributed to a better clinical response in these treatment groups. Therapy did not appear to create lasting changes in the percentage of resistant isolates or sites harboring resistant species. C1 [Haffajee, A. D.; Patel, M.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU NIDCR NIH HHS [DE-13232] NR 31 TC 44 Z9 50 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2008 VL 23 IS 2 BP 148 EP 157 DI 10.1111/j.1399-302X.2007.00403.x PG 10 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 262KY UT WOS:000253148600009 PM 18279183 ER PT J AU Figueredo, CM Rescala, B Teles, RP Teles, FP Fischer, RG Haffajee, AD Socransky, SS Gustafsson, A AF Figueredo, C. M. Rescala, B. Teles, R. P. Teles, F. P. Fischer, R. G. Haffajee, A. D. Socransky, S. S. Gustafsson, A. TI Increased interleukin-18 in gingival crevicular fluid from periodontitis patients SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE checkerboardDNA-DNA hybridization; interleukin-18; periodontitis; red complex ID SUBGINGIVAL PLAQUE; GAMMA PRODUCTION; IL-18; ARTHRITIS; CYTOKINE; DISEASE; TISSUE AB Introduction: This study aimed to measure the levels of interleukin-18 (IL-18) in inflamed shallow sites and inflamed deep sites in patients with periodontitis and to compare the data with results from inflamed shallow sites in patients with gingivitis. A secondary aim was to examine the composition of the subgingival microbiota in the sampled sites. Methods: Gingival crevicular fluid was collected from five gingivitis sites and five periodontitis sites from 18 patients with chronic periodontitis, and from five gingivitis sites from 15 patients with gingivitis. Samples from each site category were pooled and IL-18 levels were measured using an enzyme-linked immunosorbent assay. The subgingival microbiota was analyzed by checkerboard DNA-DNA hybridization. Results: All clinical parameters and gingival crevicular fluid volumes were higher in periodontitis sites compared with gingivitis sites from patients with periodontitis and gingivitis. The total amount of IL-18 was higher in periodontitis sites than gingivitis sites in both periodontitis (P = 0.018) and gingivitis (P = 0.002) patients and was higher in gingivitis sites from periodontitis patients than in those from gingivitis patients (P = 0.015). There were higher levels of Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola (red complex species) in periodontitis sites compared with gingivitis sites in both the periodontitis and gingivitis patients (P < 0.001). Conclusion: Levels of IL-18 were higher in patients with chronic periodontitis compared with patients with gingivitis, even at sites with similar pocket depths. The presence of similar levels of red complex species in gingivitis sites from periodontitis patients and from gingivitis patients suggested that the higher levels of IL-18 were not associated with a different microbial challenge. C1 [Figueredo, C. M.; Rescala, B.] Univ Estado Rio De Janeiro, Dept Periodontol, Rio De Janeiro, Brazil. [Figueredo, C. M.; Gustafsson, A.] Karolinska Inst, Dept Periodontol, Inst Odontol, S-10401 Stockholm, Sweden. [Teles, R. P.; Teles, F. P.; Haffajee, A. D.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Figueredo, CM (reprint author), Fac Odontol Secretaria Posgrad & Pesquisa, Avenida 28 De Seteembro,157 Villa Isabel, BR-20551030 Rio De Janeiro, Brazil. EM cmfigueredo@hotmail.com RI Fischer, Ricardo/F-8788-2012; Figueredo, Carlos Marcelo/H-3356-2013 OI Figueredo, Carlos Marcelo/0000-0003-0222-9231 NR 18 TC 15 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2008 VL 23 IS 2 BP 173 EP 176 DI 10.1111/j.1399-302X.2007.00408.x PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 262KY UT WOS:000253148600013 PM 18279187 ER PT J AU Gordon, BR AF Gordon, Bruce R. TI Asthma history and presentation SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID AIRWAY MUCUS HYPERSECRETION; SEASONAL ALLERGIC RHINITIS; NEAR-FATAL ASTHMA; CHRONIC COUGH; BRONCHIAL-ASTHMA; MUCOCILIARY CLEARANCE; DYSPNEA PERCEPTION; PULMONARY-FUNCTION; VARIANT ASTHMA; CHILDREN AB Asthma is suspected from a history of key symptoms, including cough, wheezing, dyspnea, chest tightness, and increased mucus production. A positive family or personal history of atopic diseases and diseases that are comorbid with asthma, such as allergic rhinitis and rhinosinusitis, is also important. The differential diagnosis of asthma is broad and includes potentially life-threatening diseases. Pediatric asthma and psychiatric mimics require special attention to prevent misdiagnosis. Differentiating asthma from these other disease states by history alone is not always possible. Because accurate diagnosis is critical to successful treatment, objective testing by spirometry and methacholine challenge should be employed. C1 [Gordon, Bruce R.] Cape Cod ENT, Hyannis, MA 02601 USA. [Gordon, Bruce R.] Harvard Univ, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Gordon, Bruce R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Gordon, Bruce R.] Cape Cod Hosp, Div Otolaryngol, Hyannis, MA USA. RP Gordon, BR (reprint author), Cape Cod ENT, Hyannis, MA 02601 USA. EM docbruce@comcast.net NR 55 TC 6 Z9 6 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2008 VL 41 IS 2 BP 375 EP + DI 10.1016/j.otc.2007.11.007 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA 281KO UT WOS:000254496000011 PM 18328375 ER PT J AU Martinez-Alvernia, EA Rudnick, JA Mankarious, LA AF Martinez-Alvernia, Efrain A. Rudnick, Jennifer A. Mankarious, Leila A. TI Transforming growth factor beta 3 increases chondrocyte proliferation and decreases apoptosis in murine cricoid cartilage in vitro SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID GROWTH-FACTOR-BETA AB OBJECTIVE: To determine if the luminal epithelium and/or exogenous transforming growth factor beta (TGF beta) affects growth of the cricoid. DESIGN: Subglottises from 20 neonatal mice were subdivided into four groups: A, five subglottises with luminal epithelium grown in basic medium; 13, five epithelium-free subglottises in basic medium; C, five epithelium-free subglottises in basic medium with supplemental TGF beta 1, and D, five epithelium-free subglottises in basic medium with supplemental TGF beta 3. RESULTS: Groups A and D demonstrated the greatest luminal area expansion. Group A rings demonstrated statistically higher chondrocyte proliferation than Groups B and C and lesser amounts of luminal apoptosis. Groups B and C rings demonstrated the least amount of cell proliferation, and greater luminal apoptosis relative to Group A. Groups A and D rings had similar apoptotic and proliferative results. CONCLUSIONS: Luminal epithelium exerts influence over the cricoid by increasing chondrocyte proliferation and decreasing the relative proportion of luminal chondrocytes that undergo apoptosis. Exogenous TGF beta 3, not TGF beta 1, also increases chondrocyte proliferation within the cricoid and appears to influence apoptosis as well. (C) 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM leila_mankarious@meei.harvard.edu FU NHLBI NIH HHS [5K08HL070116] NR 10 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2008 VL 138 IS 4 BP 435 EP 440 DI 10.1016/j.otohns.2007.11.009 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 283MY UT WOS:000254641500006 PM 18359350 ER PT J AU Mehta, RP Zhang, S Hadlock, TA AF Mehta, Ritvik P. Zhang, Song Hadlock, Tessa A. TI Novel 3-D video for quantification of facial movement SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID DYSFUNCTION; QUALITY; MOTION AB OBJECTIVES: To evaluate a novel 3-D geometry video acquisition system (3-D VAS) for quantifying facial movement. METHODS: Ten normal subjects and four patients with facial paralysis underwent recording of facial movement during three facial expressions. Facial feature points of interest were digitally marked on selected images. The maximum 3-D displacement of the brow and oral commissure and palpebral fissure width were determined. RESULTS: Test-retest reliability using the 3-D VAS in normal subjects was high (Spearman correlation coefficients 0.661-0.830, P < 0.05). The predicted ratio of left to right facial measurements was 1.00 in normal subjects, and measured mean ratios were 1.05 (brow excursion), 1.01 (palpebral fissure width), and 1.03 (oral commissure excursion), respectively, matching the prediction. The 3-D VAS reliably quantified facial movement on both sides in patients with facial paralysis. CONCLUSIONS: The novel 3-D VAS can accurately and reliably quantify facial movement in healthy subjects. It is promising as a clinical tool to quantify facial movement in patients with facial paralysis. 0 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Mehta, Ritvik P.] Univ Calif San Diego, Dept Otolaryngol, San Diego, CA 92103 USA. [Zhang, Song] Harvard Univ, Dept Math, Cambridge, MA 02138 USA. [Hadlock, Tessa A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. RP Mehta, RP (reprint author), Univ Calif San Diego, Med Ctr, Div Otolaryngol Head & Neck Surg, 200 W Arbor Dr 8895, San Diego, CA 92103 USA. EM rpmehta@ucsd.edu RI Zhang, Song/C-5294-2012 OI Zhang, Song/0000-0001-8452-4837 NR 15 TC 25 Z9 26 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2008 VL 138 IS 4 BP 468 EP 472 DI 10.1016/j.otohns.2007.12.017 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 283MY UT WOS:000254641500012 PM 18359356 ER PT J AU Merchant, SN McKenna, MJ Adams, JC Nadol, JB Fayad, J Gellibolian, R Linthicum, FH Tshiyama, A Lopez, I Ishiyama, G Baloh, R Platt, C AF Merchant, Saumil N. McKenna, Michael J. Adams, Joe C. Nadol, Joseph B., Jr. Fayad, Jose Gellibolian, Robert Linthicum, Fred H., Jr. Tshiyama, Akira Lopez, Ivan Ishiyama, Gail Baloh, Robert Platt, Christopher TI Human temporal bone consortium for research resource enhancement SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material ID 3-DIMENSIONAL VIRTUAL MODEL; INNER-EAR; VESTIBULAR DYSFUNCTION; COCHLEAR IMPLANTS; HISTOPATHOLOGY; DFNA9; PATHOLOGY; DEAFNESS; HEARING; PATIENT C1 [Merchant, Saumil N.; McKenna, Michael J.; Adams, Joe C.; Nadol, Joseph B., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. [Fayad, Jose; Gellibolian, Robert; Linthicum, Fred H., Jr.] House Ear Res Inst, Los Angeles, CA USA. [Tshiyama, Akira; Lopez, Ivan; Ishiyama, Gail; Baloh, Robert] Univ Calif Los Angeles, Los Angeles, CA USA. [Platt, Christopher] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Merchant, SN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. OI Lopez, Ivan/0000-0001-5205-7293 FU NIDCD NIH HHS [U24 DC008559, U24 DC008559-02] NR 23 TC 3 Z9 3 U1 0 U2 3 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 APR PY 2008 VL 29 IS 3 BP 271 EP 274 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 288IW UT WOS:000254980800001 PM 18364572 ER PT J AU Merchant, SN Rosowski, JJ AF Merchant, Saumil N. Rosowski, John J. TI Conductive hearing loss caused by third-window lesions of the inner ear SO OTOLOGY & NEUROTOLOGY LA English DT Review DE air-bone gap; conductive hearing loss; third window lesions ID SEMICIRCULAR CANAL DEHISCENCE; VESTIBULAR AQUEDUCT SYNDROME; AIR-BONE GAP; MIDDLE-EAR; OPERATIVE MANAGEMENT; PERILYMPHATIC GUSHER; STAPEDIAL FOOTPLATE; MIXED DEAFNESS; CHINCHILLA; SOUND AB Background: Various authors have described conductive hearing loss (CHL), defined as an air-bone gap on audiometry, in patients without obvious middle car pathologic findings. Recent investigations have suggested that many of these cases are due to disorders of the inner ear, resulting in pathologic third windows. Objective: To provide an overview of lesions of the inner ear resulting in a CHL due to a third-window mechanism. The mechanism of the CHL is explained along with a classification scheme for these disorders. We also discuss methods for diagnosis of these disorders. Data Sources: The data were compiled from a review of the literature and recent published research on middle and inner ear mechanics from our laboratory. Conclusion: A number of disparate disorders affecting the labyrinth can produce CHL by acting as a pathologic third window in the inner ear. The common denominator is that these conditions result in a mobile window on the scala vestibuli side of the cochlear partition. The CHL results by the dual mechanism of worsening of air conduction thresholds and improvement of bone conduction thresholds. Such lesions may be anatomically discrete or diffuse. Anatomically discrete lesions may be classified by location: semicircular canals (superior, lateral, or posterior canal dehiscence), bony vestibule (large vestibular aqueduct syndrome, other inner ear malformations), or the cochlea (carotid-cochlear dehiscence, X-linked deafness with stapes gusher, etc.). An example of an anatomically diffuse lesion is Paget disease, which may behave as a distributed or diffuse third window. Third-window lesions should be considered in the differential diagnosis of CHL in patients with an intact tympanic membrane and an aerated, otherwise healthy, middle ear. Clues to suspect such a lesion include a low-frequency air-bone gap with supratiormal thresholds for bone conduction, and presence of acoustic reflexes, vestibular evoked myogenic responses, or otoacoustic emission responses despite the CHL. Imaging studies can help confirm the diagnosis. C1 [Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu FU NIDCD NIH HHS [R01 DC04798, R01 DC004798-07, R01 DC000194, R01 DC004798] NR 52 TC 100 Z9 104 U1 1 U2 17 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 APR PY 2008 VL 29 IS 3 BP 282 EP 289 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 288IW UT WOS:000254980800003 PM 18223508 ER PT J AU Hara, H Lin, YJ Zhu, X Tai, HC Ezzelarab, M Balamarugan, AN Bottino, R Houser, SL Cooper, DKC AF Hara, Hidetaka Lin, Yih Jyh Zhu, Xiaocheng Tai, Hao-Chih Ezzelarab, Mohamed Balamarugan, A. N. Bottino, Rita Houser, Stuart L. Cooper, David K. C. TI Safe induction of diabetes by high-dose streptozotocin in pigs (vol 36, pg 31, 2008) SO PANCREAS LA English DT Correction C1 [Balamarugan, A. N.; Bottino, Rita] Univ Pittsburgh, Med Ctr, Dept Pediat, Div Immunogenet, Pittsburgh, PA USA. [Houser, Stuart L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2008 VL 36 IS 3 BP 328 EP 328 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 282TI UT WOS:000254589700021 ER PT J AU Frazier, AL Rumcheva, P Olson, T Giller, R Cushing, B Cullen, J Marina, N London, WB AF Frazier, A. Lindsay Rumcheva, Paviina Olson, Thomas Giller, Roger Cushing, Barbara Cullen, John Marina, Neyssa London, Wendy B. TI Application of the adult International Germ Cell Classification system to pediatric malignant non-seminomatous germ cell tumors: A report from the children's oncology group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE germ cell tumors; International Germ Cell Classification; pediatric germ cell tumors; risk stratification; tumor markers ID PROGNOSTIC-FACTORS; INTERGROUP; ADOLESCENTS; CISPLATIN; ETOPOSIDE; BLEOMYCIN; INFANTS AB Background. The purpose of this analysis is to explore whether the International Germ Cell Classification Consensus (IGCCC) tumor marker criteria, developed for adult males with metastatic malignant germ cell tumors (MGCT), are prognostic among pediatric patients and whether tumor marker data may be relevant in pediatric risk stratification. Procedure. The IGCCC was applied to 436 pediatric germ cell patients treated on Pediatric Intergroup Studies from 1990 to 1996. Multivariable Cox proportional hazards model identified prognostic variables; survival rates among IGCCC risk groups were compared using the log-rank test. Concordance and relative performance of IGCCC versus COG risk stratification was evaluated. Results. Applying the IGCCC, 21% of pediatric patients were good risk (GR), 35% intermediate risk (IR), and 44% poor risk (PR). Only modest concordance between IGCCC and COG stratification systems was noted (49%). Nonetheless, the IGCCC identified a group of PR patients who had significantly worse event-free survival (EFS) versus GR/IR patients (6-year EFS 80% vs. 91 V, which was similar to the difference observed using the COG system (6-year EFS 77% vs. 90%). The IGCCC performed well within subgroups for which the IGCCC is not intended (prepubertal, female, and non-metastatic patients). Conclusions. Applying the IGCCC system to pediatric patients produces a different stratification than does the application of the COG system, although both are prognostic. Development of a de novo pediatric prognostic classification is warranted. C1 [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rumcheva, Paviina; London, Wendy B.] Univ Florida, Dept Epidemiol & Hlth Policy Res, Childrens Oncol Grp, Gainesville, FL USA. [Olson, Thomas] Emory Univ, Atlanta, GA 30322 USA. [Giller, Roger] Childrens Hosp, Denver, CO 80218 USA. [Cushing, Barbara] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Cullen, John] Presbyterian St Lukes Med Ctr, Denver, CO USA. RP Frazier, AL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM lindsay_frazier@dfci.harvard.edu FU NCI NIH HHS [U10 CA029139, U10 CA098413, U10-CA29139, U10-CA98413-02] NR 13 TC 13 Z9 14 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2008 VL 50 IS 4 BP 746 EP 751 DI 10.1002/pbc.21304 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 269PK UT WOS:000253661200004 PM 18085675 ER PT J AU Opoka, RO Xia, ZQ Bangirana, P John, CC AF Opoka, Robert O. Xia, Zongqi Bangirana, Paul John, Chandy C. TI Inpatient mortality in children with clinically diagnosed malaria as compared with microscopically confirmed malaria SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE malaria; microscopy; Plasmodium falciparum; mortality; children ID AFRICAN CHILDREN; PLASMODIUM-FALCIPARUM; FEBRILE ILLNESS; ANTIMALARIAL TREATMENT; TRANSMISSION; UGANDA; TANZANIA; TESTS; AREA; BACTEREMIA AB Background: Inpatient treatment for malaria without microscopic confirmation of the diagnosis occurs commonly in sub-Saharan Africa. Differences in mortality in children who are tested by microscopy for Plasmodium falciparum infection as compared with those not tested are not well characterized. Methods: A retrospective chart review was conducted of all children up to 15 years of age admitted to Mulago Hospital, Kampala, Uganda from January 2002 to July 2005, with a diagnosis of malaria and analyzed according to microscopy testing for P. falciparum. Results: A total of 23,342 children were treated for malaria during the study period, 991 (4.2%) of whom died. Severe malarial anemia in 7827 (33.5%) and cerebral malaria in 1912 (8.2%) were the 2 common causes of malaria-related admissions. Children who did not receive microscopy testing had a higher case fatality rate than those with a positive blood smear (7.5% versus 3.2%, P < 0.001). After adjustment for age, malaria complications, and comorbid conditions, children who did not have microscopy performed or had a negative blood smear had a higher risk of death than those with a positive blood smear [odds ratio (OR): 3.49, 95% confidence interval (CI): 2.88-4.22, P < 0.001; and OR: 1.59, 95% CI: 1.29-1.96, P < 0.001, respectively]. Conclusions: Diagnosis of malaria in the absence of microscopic confirmation is associated with significantly increased mortality in hospitalized Ugandan children. Inpatient diagnosis of malaria should be supported by microscopic or rapid diagnostic test confirmation. C1 Makerere Univ, Sch Med, Mulgao Hosp, Dept Pediat & Child Hlth, Kampala, Uganda. [Xia, Zongqi] Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02115 USA. [Bangirana, Paul] Makerere Univ, Inst Psychol, Dept Mental Hlth & Community Psychol, Kampala, Uganda. [John, Chandy C.] Univ Minnesota, Dept Pediat, Global Pediat Program, Minneapolis, MN 55455 USA. RP Opoka, RO (reprint author), Makerere Univ, Sch Med, Mulgao Hosp, Dept Pediat & Child Hlth, Box 7051, Kampala, Uganda. EM opokabob@yahoo.com RI John, Chandy/B-4164-2008; OI Bangirana, Paul/0000-0002-7136-0594 FU FIC NIH HHS [R21 TW-006794, R21 TW006794-03S2, R21 TW006794] NR 37 TC 22 Z9 22 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2008 VL 27 IS 4 BP 319 EP 324 DI 10.1097/INF.0b013e31815d74dd PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 283NN UT WOS:000254643100007 PM 18316995 ER PT J AU Meropol, SB Glick, HA Asch, DA AF Meropol, Sharon B. Glick, Henry A. Asch, David A. TI Age inconsistency in the American Academy of Pediatrics guidelines for acute otitis media SO PEDIATRICS LA English DT Article; Proceedings Paper CT 22nd International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 24-27, 2006 CL Lisbon, PORTUGAL DE antibiotic use; child; cost-effectiveness; guidelines; otitis media ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-EAR EFFUSION; ANTIBIOTIC USE; COST-EFFECTIVENESS; CLINICAL-TRIAL; PNEUMOCOCCAL RESISTANCE; TYMPANOCENTESIS SKILLS; DIAGNOSTIC-ACCURACY; TREATMENT OPTIONS AB OBJECTIVE. The American Academy of Pediatrics acute otitis media guidelines could reduce antibiotic use. The objective was to compare strategies for diagnosing and treating otitis: ( 1) a commonly used, 2-criteria strategy, ( 2) the guidelines' 3-criteria algorithm, and ( 3) initially watching without antibiotics. METHODS. A decision analysis was performed with literature-based parameter. The target population was children presenting to primary care physicians with possible otitis media. Main outcomes were antibiotic use, sick days, mild adverse drug events, and number needed to treat/avoided sick day. RESULTS. For children 2 to <6 months of age, compared with the 2-criteria strategy, guideline use predicted 21% less antibiotic use, 13% more sick days, and 23% fewer adverse drug events; the number needed to treat for the 2-criteria strategy versus the American Academy of Pediatrics strategy was 1.2 children per avoided sick day. For children 6 to <24 months of age, guideline use, compared with the 2-criteria strategy, predicted 26% less antibiotic use, 14% more sick days, and 28% fewer adverse drug events; the number needed to treat for the 2-criteria strategy versus the American Academy of Pediatrics strategy was 1.4 children per avoided sick day. For children >2 years of age, guideline use, compared with the 2-criteria strategy, predicted 67% less antibiotic use, 4% more sick days, and 68% fewer adverse drug events. The number needed to treat for the guideline strategy versus the watch strategy was 6.3 children per avoided sick day; that for the 2-criteria strategy versus the guideline strategy was 12.3. Guideline use for children 2 years implies that our number needed to treat to avoid a sick day is 1.4; for children >2, guideline use implies we are willing to treat at least 6.3 children to avoid a sick day. Thus, the guidelines imply a greater willingness to treat older children, compared with younger children. CONCLUSIONS. The American Academy of Pediatrics guidelines are inconsistent in their outcomes across age groups. Guideline implementation under age 2 reduces antibiotic use but at a relatively heavy cost of sick days and parental missed work days. This trade-off may be particularly unfavorable for working parents, who might reasonably prefer greater antibiotic use. C1 [Meropol, Sharon B.; Asch, David A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Meropol, Sharon B.] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Glick, Henry A.; Asch, David A.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Glick, Henry A.; Asch, David A.] Univ Penn, Sch Med, Div Gen Internal Med, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Meropol, SB (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 108 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM meropols@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU AHRQ HHS [HS10399] NR 60 TC 5 Z9 6 U1 0 U2 2 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 APR PY 2008 VL 121 IS 4 BP 657 EP 668 DI 10.1542/peds.2007-1913 PG 12 WC Pediatrics SC Pediatrics GA 282OJ UT WOS:000254576800001 PM 18381528 ER PT J AU Mansbach, JM Clark, S Christopher, NC LoVecchio, F Kunz, S Acholonu, U Camargo, CA AF Mansbach, Jonathan M. Clark, Sunday Christopher, Norman C. LoVecchio, Frank Kunz, Sarah Acholonu, Uchechi Camargo, Carlos A., Jr. TI Prospective multicenter study of bronchiolitis: Predicting safe discharges from the emergency department SO PEDIATRICS LA English DT Article DE bronchiolitis; discharge; emergency department; risk factors; guideline ID SYNCYTIAL VIRUS-INFECTION; INVESTIGATORS COLLABORATIVE NETWORK; RESPIRATORY-TRACT INFECTION; FULL-TERM INFANTS; RISK-FACTORS; HOSPITALIZED INFANTS; RHINOVIRUS ILLNESSES; UNITED-STATES; US CHILDREN; 1ST YEAR AB OBJECTIVE. Bronchiolitis is the leading cause of hospitalization for infants. Our objective was to identify factors associated with safe discharge to home from the emergency department. METHODS. We conducted a prospective cohort study during 2 consecutive bronchiolitis seasons, from 2004 to 2006. Thirty US emergency departments contributed data. All patients were <2 years of age and had a final emergency department attending physician diagnosis of bronchiolitis. Using multivariate logistic regression, a low-risk model was developed with a random half of the data and then validated with the other half. RESULTS. Of 1456 enrolled patients, 837 ( 57%) were discharged home from the emergency department. The following factors predicted safe discharge to home: age of >= 2 months, no history of intubation, a history of eczema, age-specific respiratory rates ( < 45 breaths per minute for 0-1.9 months, <43 breaths per minute for 2-5.9 months, and <40 breaths per minute for 6-23.9 months), no/mild retractions, initial oxygen saturation of >= 94%, fewer albuterol or epinephrine treatments in the first hour, and adequate oral intake. The importance of each factor varied slightly according to age, but the comprehensive model ( developed and validated for all children <2 years of age) yielded an area under the receiver operating characteristic curve of 0.81, with a good fit of the data. CONCLUSIONS. This large multicenter study of children presenting to the emergency department with bronchiolitis identified several factors associated with safe discharge, including cut points for respiratory rate and oxygen saturation. Although the low-risk model requires further study, we believe that it will assist clinicians evaluating children with bronchiolitis and may help reduce some unnecessary hospitalizations. C1 [Mansbach, Jonathan M.] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Clark, Sunday; Kunz, Sarah; Acholonu, Uchechi; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Christopher, Norman C.] Akron Childrens Hosp, Dept Med, Akron, OH USA. [LoVecchio, Frank] Maricopa Cty Gen Hosp, Dept Emergency Med, Phoenix, AZ USA. RP Mansbach, JM (reprint author), Childrens Hosp Boston, Dept Med, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 49 TC 54 Z9 54 U1 0 U2 2 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 APR PY 2008 VL 121 IS 4 BP 680 EP 688 DI 10.1542/peds.2007-1418 PG 9 WC Pediatrics SC Pediatrics GA 282OJ UT WOS:000254576800004 PM 18381531 ER PT J AU Greenspan, SI Brazelton, TB Cordero, J Solomon, R Bauman, ML Robinson, R Shanker, S Breinbauer, C AF Greenspan, Stanley I. Brazelton, T. Berry Cordero, Jose Solomon, Richard Bauman, Margaret L. Robinson, Ricki Shanker, Stuart Breinbauer, Cecilia TI Guidelines for early identification, screening, and clinical management of children with autism spectrum disorders SO PEDIATRICS LA English DT Editorial Material ID YOUNG-CHILDREN; LANGUAGE INTERVENTION; TRIAL C1 [Greenspan, Stanley I.] George Washington Univ, Dept Psychiat Behav Sci & Pediat, Washington, DC USA. [Brazelton, T. Berry] Harvard Univ, Sch Med, Dept Pediat Emeritus, Boston, MA USA. [Bauman, Margaret L.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Brazelton, T. Berry] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Brazelton, T. Berry] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Brazelton, T. Berry] Massachusetts Gen Hosp, LADDERS, Boston, MA 02114 USA. [Cordero, Jose] Univ Puerto Rico, Sch Publ Hlth, San Juan, PR 00936 USA. [Solomon, Richard] Ann Arbor Ctr Dev & Behav Pediat, Ann Arbor, MI USA. [Robinson, Ricki] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Shanker, Stuart] York Univ, Dept Philosophy & Psychol, Toronto, ON M3J 2R7, Canada. [Breinbauer, Cecilia] ICDL Grad Sch, Interdisciplinary Council Dev & Learning Disorder, Kentfield, CA USA. RP Greenspan, SI (reprint author), 7201 Glenbrook Rd, Bethesda, MD 20814 USA. EM stanleygreenspan@gmail.com NR 23 TC 14 Z9 15 U1 1 U2 10 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 APR PY 2008 VL 121 IS 4 BP 828 EP 830 DI 10.1542/peds.2007-3833 PG 3 WC Pediatrics SC Pediatrics GA 282OJ UT WOS:000254576800020 PM 18381546 ER PT J AU Hopwood, CJ Baker, KL Morey, LC AF Hopwood, Christopher J. Baker, Kay L. Morey, Leslie C. TI Personality and drugs of choice SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE substance use; drugs of choice; personality; exterrializing; personality assessment inventory ID COCAINE-INDUCED PARANOIA; MENTAL-DISORDERS; CONNECTIONS; PSYCHOSIS; DIAGNOSES AB Although drug preference has been studied from the perspectives of individual differences and comorbid psychopathology, research incorporating both of these levels of analysis has been limited. In the current study, inpatients in a substance abuse treatment facility who reported preferences for alcohol, marijuana, methamphetamines, cocaine, heroin, or crack cocaine were compared in terms of their scores on measures of higher-order personality variables and psychopathology constructs representing lower-order elements of these factors. Results suggested that a broad externalizing dimension differentiated heroin users from alcohol, marijuana, and cocaine users. With the single exception that crack users remained more paranoid than alcohol users, p ychopathology variables did not provide more specific discriminatory ability after broad personality factors were controlled. Implications for substance use research are discussed, with a focus on the utility of integrating individual differences and psychopathology constructs. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Hopwood, Christopher J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hopwood, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hopwood, Christopher J.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Baker, Kay L.] Cent Texas Treatment Ctr, Granger, TX 76530 USA. [Morey, Leslie C.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. RP Hopwood, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman WAC 812, Boston, MA 02114 USA. EM chopwood@partners.org RI Morey, Leslie/B-5617-2008 OI Morey, Leslie/0000-0001-7711-5568 NR 19 TC 15 Z9 15 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD APR PY 2008 VL 44 IS 6 BP 1413 EP 1421 DI 10.1016/j.paid.2007.12.009 PG 9 WC Psychology, Social SC Psychology GA 288GV UT WOS:000254975200012 ER PT J AU Liu, G Gurubhagavatula, S Zhou, W Wang, Z Yeap, BY Asomaning, K Su, L Heist, R Lynch, TJ Christiani, DC AF Liu, G. Gurubhagavatula, S. Zhou, W. Wang, Z. Yeap, B. Y. Asomaning, K. Su, L. Heist, R. Lynch, T. J. Christiani, D. C. TI Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib SO PHARMACOGENOMICS JOURNAL LA English DT Article DE EGFR; genetic polymorphisms; lung cancer; treatment outcomes ID DINUCLEOTIDE REPEAT; INTRON-1 POLYMORPHISM; HAPLOTYPE INFERENCE; GENE PREDICT; EGFR GENE; MUTATIONS; CHEMOTHERAPY; SENSITIVITY; TOXICITY; TUMORS AB The-216G/T, -191C/A, intron 1 and Arg497Lys epidermal growth factor receptor ( EGFR) polymorphisms were evaluated in 92 advanced non-small-cell lung cancer patients treated with gefitinib, an EGFR tyrosine-kinase inhibitor. Improved progression free survival (PFS) was found in patients homozygous for the shorter lengths of intron 1 polymorphism (S/S; S = 16 or fewer CA repeats; log-rank test (LRT) P = 0.03) and for patients carrying any T allele of the -216G/T polymorphism ( LRT, P = 0.005). When considered together, patients with intron 1 S/S genotype and at least one T allele of -216G/T had improved PFS ( LRT P = 0.0006; adjusted hazard ratio (AHR), 0.60 (95% confidence interval, 0.36-0.98)) and overall survival ( LRT P = 0.02; AHR, 0.60 (0.36-1.00)) when compared with all others. The T allele of -216G/T was also associated with significantly higher rates of stable disease/partial response (P=0.01) and a significantly higher risk of treatment-related rash/diarrhea (P = 0.004, multivariate model). EGFR intron 1 and -216G/T polymorphisms influence clinical outcomes in gefitinibtreated non-small-cell lung cancer patients. C1 [Liu, G.; Gurubhagavatula, S.] Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Liu, G.; Gurubhagavatula, S.; Yeap, B. Y.; Heist, R.; Lynch, T. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA USA. [Liu, G.; Gurubhagavatula, S.; Yeap, B. Y.; Heist, R.; Lynch, T. J.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Liu, G.; Zhou, W.; Wang, Z.; Asomaning, K.; Su, L.; Heist, R.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Liu, G.; Gurubhagavatula, S.] Univ Toronto, Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M5G 2M9, Canada. [Christiani, D. C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Liu, G (reprint author), Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, 610 Univ Ave,Room 7-124, Toronto, ON M5G 2M9, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA110822, CA109193, CA74386, ES/CA 06409]; NIEHS NIH HHS [ES00002] NR 38 TC 69 Z9 71 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD APR PY 2008 VL 8 IS 2 BP 129 EP 138 DI 10.1038/sj.tpj.6500444 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 276EK UT WOS:000254123900007 PM 17375033 ER PT J AU Hu, K Peng, CK Huang, NE Wu, Z Lipsitz, LA Cavallerano, J Novak, V AF Hu, Kun Peng, C. K. Huang, Norden E. Wu, Zhaohua Lipsitz, Lewis A. Cavallerano, Jerry Novak, Vera TI Altered phase interactions between spontaneous blood pressure and flow fluctuations in type 2 diabetes mellitus: Nonlinear assessment of cerebral autoregulation SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE nonstationary; nonlinear phase interaction; instantaneous phase shift; cerebral autoregulation; cerebral blood flow velocity; multimodal pressure-flow analysis ID NONSTATIONARY TIME-SERIES; FREQUENCY-DOMAIN ANALYSIS; CAROTID-ARTERY-DISEASE; HEAD-UP TILT; VELOCITY; HUMANS; STROKE; OSCILLATIONS; REACTIVITY; DYNAMICS AB Cerebral autoregulation is an important mechanism that involves dilatation and constriction in arterioles to maintain relatively stable cerebral blood flow in response to changes of systemic blood pressure. Traditional assessments of autoregulation focus on the changes of cerebral blood flow velocity in response to large blood pressure fluctuations induced by interventions. This approach is not feasible for patients with impaired autoregulation or cardiovascular regulation. Here we propose a newly developed technique the multimodal pressure-flow (MMPF) analysis, which assesses autoregulation by quantifying nonlinear phase interactions between spontaneous oscillations in blood pressure and flow velocity during resting conditions. We show that cerebral autoregulation in healthy subjects can be characterized by specific phase shifts between spontaneous blood pressure and flow velocity oscillations, and the phase shifts are significantly reduced in diabetic subjects. Smaller phase shifts between oscillations in the two variables indicate more passive dependence of blood flow velocity on blood pressure, thus suggesting impaired cerebral autoregulation. Moreover, the reduction of the phase shifts in diabetes is observed not only in previously-recognized effective region of cerebral autoregulation (< 0.1 Hz), but also over the higher frequency range from similar to 0.1 to 0.4 Hz. These findings indicate that type 2 diabetes mellitus alters cerebral blood flow regulation over a wide frequency range and that this alteration can be reliably assessed from spontaneous oscillations in blood pressure and blood flow velocity during resting conditions. We also show that the MMPF method has better performance than traditional approaches based on Fourier transform, and is more suitable for the quantification of nonlinear phase interactions between nonstationary biological signals such as blood pressure and blood flow. (c) 2007 Elsevier B.V. All rights reserved. C1 [Hu, Kun; Lipsitz, Lewis A.; Novak, Vera] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02115 USA. [Peng, C. K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA USA. [Peng, C. K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Margret & HA Rey Inst Nonlinear Dynam Med, Boston, MA USA. [Huang, Norden E.] Natl Cent Univ, Res Ctr Adapt Data Anal, Chungli 32054, Taiwan. [Huang, Norden E.] Acad Sinica, Res Ctr Appl Sci, Div Mech, Taipei 115, Taiwan. [Wu, Zhaohua] Ctr Ocean Land Atmosphere Studies, Calverton, MD USA. [Lipsitz, Lewis A.] Hebrew SeniorLife, Boston, MA USA. [Cavallerano, Jerry] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Hu, K (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gerontol, 812 Stoneman Bldg,330 Brookline Ave, Boston, MA 02115 USA. EM khu@bidmc.harvad.edu; vnovak@bidmc.harvard.edu RI Peng, Chung-Kang/E-1489-2011; Wu, Zhaohua/N-7102-2013; OI Peng, Chung-Kang/0000-0003-3666-9833; Wu, Zhaohua/0000-0003-1660-0724 FU NCRR NIH HHS [M01 RR001032-290856, M01 RR001032, M01 RR001032-30A10856, P41 RR013622, P41 RR013622-05S10024]; NIA NIH HHS [P01 AG004390, P01 AG004390-24S1, P60 AG008812, P60 AG008812-15S2]; NINDS NIH HHS [R01 NS045745, R01 NS045745-04, R41 NS053128, R41 NS053128-01A2] NR 66 TC 22 Z9 22 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD APR 1 PY 2008 VL 387 IS 10 BP 2279 EP 2292 DI 10.1016/j.physa.2007.11.052 PG 14 WC Physics, Multidisciplinary SC Physics GA 275YF UT WOS:000254107500007 PM 18432311 ER PT J AU Fisher, DE AF Fisher, David E. TI Melanocyte signaling and transcriptional responses in skin and skin cancer SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. 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 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 243 EP 243 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700020 ER PT J AU Cui, RT Xin, H Yang, G Keerthivasan, S Zhou, AY Li, YZ Qin, J Denning, M Nickoloff, B Feng, W AF Cui, Rutao Xin, Hong Yang, Guang Keerthivasan, Shipla Zhou, Anyu Li, Yitang Qin, Jianzhong Denning, Mitchell Nickoloff, Brian Feng, Wei TI Inhibition of PAX3 by TGF-beta;; modulates melanocytes viability SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Cui, Rutao; Xin, Hong; Keerthivasan, Shipla; Qin, Jianzhong; Denning, Mitchell; Nickoloff, Brian; Feng, Wei] Loyola Univ Chicago, Chicago, IL USA. [Yang, Guang; Zhou, Anyu; Li, Yitang] Harvard Univ, Childrens Hosp Boston, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 268 EP 268 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700105 ER PT J AU Hodi, FS AF Hodi, F. Stephen TI Effective anti-tumor immunity without serious autoimmunity in previously vaccinated patients receiving CTLA-4 blockade SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Program, 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 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 271 EP 272 PG 2 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700118 ER PT J AU Sundstrom, E Pielberg, GR Golovko, A Curik, I Lennartsson, J Seltenhammer, MH Druml, T Binns, M Fitzsimmons, C Lindgren, G Sandberg, K Baumung, R Vetterlein, M Stromberg, S Grabherr, M Wade, C Lindblad-Toh, K Ponten, F Heldin, CH Solkner, J Andersson, L AF Sundstrom, Elisabeth Pielberg, Gerli Rosengren Golovko, Anna Curik, Ino Lennartsson, Johan Seltenhammer, Monika H. Druml, Thomas Binns, Matthew Fitzsimmons, Carolyn Lindgren, Gabriella Sandberg, Kaj Baumung, Roswitha Vetterlein, Monika Stromberg, Sara Grabherr, Manfred Wade, Claire Lindblad-Toh, Kerstin Ponten, Fredrik Heldin, Carl-Henrik Solkner, Johann Andersson, Leif TI Cis-acting regulatory mutation causes premature hair greying and susceptibility to melanoma in the horse SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Sundstrom, Elisabeth; Lindgren, Gabriella; Sandberg, Kaj; Andersson, Leif] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden. [Pielberg, Gerli Rosengren; Golovko, Anna; Lindblad-Toh, Kerstin; Andersson, Leif] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden. [Curik, Ino] Univ Zagreb, Fac Agr, Dept Anim Sci, Zagreb 41000, Croatia. [Lennartsson, Johan; Heldin, Carl-Henrik] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden. [Seltenhammer, Monika H.] Univ Vet Med, Dept Clin Surg & Ophthalmol, Vienna, Austria. [Druml, Thomas; Baumung, Roswitha] Univ Nat Resources & Appl Life Sci, Dept Sustainable Agr Syst, A-1180 Vienna, Austria. [Binns, Matthew] Univ London Royal Vet Coll, London NW1 0TU, England. [Vetterlein, Monika] Med Univ Vienna, Dept Cell Biol & Ultrastruct Res, Ctr Anat & Cell Biol, Vienna, Austria. [Stromberg, Sara; Ponten, Fredrik] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Grabherr, Manfred; Wade, Claire; Lindblad-Toh, Kerstin] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Wade, Claire] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 274 EP 275 PG 2 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700127 ER PT J AU Hodi, FS Zhou, J Yuen, NK Friedlander, P Corless, C Heinrich, M Jiang, XF Widlund, HR Fisher, DE AF Hodi, F. Stephen Zhou, Jun Yuen, Noah K. Friedlander, Philip Corless, Christopher Heinrich, Michael Jiang, Xiaofeng Widlund, Hans R. Fisher, David E. TI Targeting KIT mutated melanoma SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Hodi, F. Stephen; Zhou, Jun; Yuen, Noah K.; Friedlander, Philip; Jiang, Xiaofeng; Widlund, Hans R.; Fisher, David E.] Dana Farber Canc Inst, Clin Director Melanoma Program, Boston, MA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. 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 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 286 EP 286 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700167 ER PT J AU Osawa, M AF Osawa, Masatake TI Melanocyte stem cells: as a model to study stem cell biology SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Osawa, Masatake] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. 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 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 294 EP 294 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700193 ER PT J AU Zheng, B Jeong, HNJ Asara, J Yuan, YY Granter, S Chin, L Cantley, L AF Zheng, Bin Jeong, Hyeong-Nam Joesph Asara, John Yuan, Yuan-Ying Granter, Scott Chin, Lynda Cantley, Lewis TI Oncogenic BRAF negatively regulates the LKB1-AMPK signaling to promote melanoma cell proliferation SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Zheng, Bin; Asara, John; Yuan, Yuan-Ying; Cantley, Lewis] Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02138 USA. [Jeong, Hyeong-Nam Joesph; Chin, Lynda] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. [Granter, Scott] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Cambridge, MA 02138 USA. [Zheng, Bin; Asara, John; Yuan, Yuan-Ying; Cantley, Lewis] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. 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 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 312 EP 312 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700255 ER PT J AU Liao, EC Taghinia, AH Nguyen, LP Yueh, JH May, JW Orgill, DP AF Liao, Eric C. Taghinia, Amir H. Nguyen, Lisa P. Yueh, Janet H. May, James W., Jr. Orgill, Dennis P. TI Incidence of hematoma complication with heparin venous thrombosis prophylaxis after TRAM flap breast reconstruction SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Association-of-Plastic-Surgeons CY MAY 22, 2007 CL Coeur dAlene, ID SP Amer Assoc Plast Surg ID LOW-MOLECULAR-WEIGHT; DEEP-VEIN THROMBOSIS; MAJOR ABDOMINAL-SURGERY; UNFRACTIONATED HEPARIN; PULMONARY-EMBOLISM; STANDARD HEPARIN; THROMBOEMBOLISM; PREVENTION; ABDOMINOPLASTY; MULTICENTER AB Background: Randomized controlled studies provide ample evidence that heparin is effective in reducing the risk of thromboembolic complications. Nevertheless, plastic surgeons are often reluctant to use heparin chemoprophylaxis for fear of postoperative bleeding. The authors investigated whether heparin chemoprophylaxis was associated with postoperative hematoma that required evacuation in patients who underwent transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. Methods: A multicenter retrospective review of consecutive TRAM flap cases identified 679 patients, 392 in the heparin-treated group and 287 in the control group. The post hoc sample sizes were adequate to detect a 5 percent difference in hematoma rate with 89 percent power at an alpha level of 5 percent (p < 0.05). Outcome measures of reoperative hematoma, deep vein thrombosis, and pulmonary embolism were recorded. Results: Reoperative hematoma occurred in 0.5 percent of patients in the heparin-treated group and 1.0 percent of patients in the control group; this difference was not statistically significant (p = 0.66). Thromboembolic events were detected at a low rate (0.8 percent in the heparin-treated group versus 1.4 percent in the untreated group; p = 0.46). Conclusions: The use of heparin for venous thrombotic prophylaxis did not increase the risk of reoperative hematoma after breast reconstruction with abdominal tissue. The authors propose a risk assessment that balances a statistical hematoma rate of 0.5 to 5 percent (clinically observed rate, 0.5 percent) with use of heparin prophylaxis against a rare (clinically observed rate, 1.4 percent) but morbid occurrence of thromboembolic complications when chemoprophylaxis is omitted. C1 [Orgill, Dennis P.] Harvard Univ, Plast Surg Off, Massachusetts Gen Hosp,Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Orgill, DP (reprint author), Harvard Univ, Plast Surg Off, Massachusetts Gen Hosp,Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org OI Orgill, Dennis/0000-0002-8279-7310 NR 35 TC 26 Z9 26 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2008 VL 121 IS 4 BP 1101 EP 1107 DI 10.1097/01.prs.0000302454.43201.83 PG 7 WC Surgery SC Surgery GA 277AA UT WOS:000254183600004 PM 18349626 ER PT J AU Bhattacharyya, T Mehta, P Smith, RM Pomahac, B AF Bhattacharyya, Timothy Mehta, Priyesh Smith, R. Malcolm Pomahac, Bohdan TI Routine use of wound vacuum-assisted closure does not allow coverage delay for open tibia fractures SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SOFT-TISSUE INJURIES; SEVERE COMPOUND FRACTURES; MANAGEMENT; THERAPY; RECONSTRUCTION; COMPLICATIONS; FOUNDATION; EXPERIENCE; TRAUMA; TRENDS AB Background: Prevention of infection is a paramount concern after open fracture of the tibia. Previous studies have shown that delay in soft-tissue coverage may raise infection rates. Use of vacuum-assisted closure devices in open fracture wounds has become common. The authors analyzed whether use of the vacuum-assisted closure sponge can allow delay of flap coverage for open tibia fractures without an increase in infection rate. Methods: The authors identified 38 patients with Gustilo grade IIIB open fractures from their trauma registry with a minimum I-year follow-up. From the medical record, the authors collected information on the time from injury to definitive wound coverage, type of fixation, type of coverage, and demographics. Infected patients were defined as patients that required surgical debridement after coverage with positive cultures. Results: Patients who underwent definitive coverage within 7 days had a significantly decreased rate of infection (12.5 percent) compared with patients who had coverage at 7 days or more after injury (57 percent) (p < 0.008). The overall infection rate was 36 percent with routine use of the vacuum-assisted closure sponge. Patients who developed infection had a greater mean time to coverage than patients who did not develop infection (8.9 days versus 4.8 days; p < 0.029). Conclusions: Routine use of vacuum-assisted closure with open tibia fractures is safe and provides a good primary dressing over open wounds. For Gustilo grade IIIB tibia fractures, vacuum-assisted closure therapy does not allow delay of soft-tissue coverage past 7 days without a concomitant elevation in infection rates. C1 [Bhattacharyya, Timothy] Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Orthoped Trauma Serv, Boston, MA 02118 USA. Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02118 USA. RP Bhattacharyya, T (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Orthoped Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02118 USA. NR 25 TC 49 Z9 56 U1 2 U2 5 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 APR PY 2008 VL 121 IS 4 BP 1263 EP 1266 DI 10.1097/01.prs.0000305536.09242.a6 PG 4 WC Surgery SC Surgery GA 277AA UT WOS:000254183600023 PM 18349645 ER PT J AU Kelly, KA Bardeesy, N Anbazhagan, R Gurumurthy, S Berger, J Alencar, H DePinho, RA Mahmood, U Weissleder, R AF Kelly, Kimberly A. Bardeesy, Nabeel Anbazhagan, Rajesh Gurumurthy, Sushma Berger, Justin Alencar, Herlen DePinho, Ronald A. Mahmood, Umar Weissleder, Ralph TI Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma SO PLOS MEDICINE LA English DT Article ID EARLY-DIAGNOSIS; PHAGE DISPLAY; MOUSE MODEL; CANCER; PROTEIN; PEPTIDE; CELLS; MICE; CARCINOMA; SELECTION AB Background Pancreatic ductal adenocarcinoma 9PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents. Methods and Findings Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides 9PTP) were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models. Conclusions Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans. C1 [Kelly, Kimberly A.; Anbazhagan, Rajesh; Alencar, Herlen; Mahmood, Umar; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Kelly, Kimberly A.; Anbazhagan, Rajesh; Alencar, Herlen; Mahmood, Umar; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Bardeesy, Nabeel; Gurumurthy, Sushma; Berger, Justin; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bardeesy, Nabeel; Gurumurthy, Sushma; Berger, Justin; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Genet, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, Boston, MA 02115 USA. [Mahmood, Umar; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Kelly, KA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. EM kkelly9@partners.org FU NCI NIH HHS [P50 CA086355, K01 CA104647, K01 CA104647-03, P01 CA117969, P01-CA117969-01, P50-CA86355] NR 39 TC 126 Z9 129 U1 2 U2 22 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 APR PY 2008 VL 5 IS 4 BP 657 EP 668 AR e85 DI 10.1371/journal.pmed.0050085 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 293XX UT WOS:000255369800020 PM 18416599 ER PT J AU Harris, JB LaRocque, RC Chowdhury, F Khan, AI Logvinenko, T Faruque, ASG Ryan, ET Qadri, F Calderwood, SB AF Harris, Jason B. LaRocque, Regina C. Chowdhury, Fahima Khan, Ashraful I. Logvinenko, Tanya Faruque, Abu S. G. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. TI Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID SUBUNIT-WHOLE CELL; ANTIBODY-RESPONSE; IMMUNE-RESPONSES; BLOOD-GROUP; MUCOSAL; DISEASE; VACCINE; O139; PROTECTION; CHILDREN AB Background: Despite recent progress in understanding the molecular basis of Vibrio cholerae pathogenesis, there is relatively little knowledge of the factors that determine the variability in human susceptibility to V. cholerae infection. Methods and Findings: We performed an observational study of a cohort of household contacts of cholera patients in Bangladesh, and compared the baseline characteristics of household members who went on to develop culture-positive V. cholerae infection with individuals who did not develop infection. Although the vibriocidal antibody is the only previously described immunologic marker associated with protection from V. cholerae infection, we found that levels of serum IgA specific to three V. cholerae antigens-the B subunit of cholera toxin, lipopolysaccharide, and TcpA, the major component of the toxin-co-regulated pilus-also predicted protection in household contacts of patients infected with V. cholerae O1, the current predominant cause of cholera. Circulating IgA antibodies to TcpA were also associated with protection from V. cholerae O139 infection. In contrast, there was no association between serum IgG antibodies specific to these three antigens and protection from infection with either serogroup. We also found evidence that host genetic characteristics and serum retinol levels modify susceptibility to V. cholerae infection. Conclusions: Our observation that levels of serum IgA (but not serum IgG) directed at certain V. cholerae antigens are associated with protection from infection underscores the need to better understand anti-V. cholerae immunity at the mucosal surface. Furthermore, our data suggest that susceptibility to V. cholerae infection is determined by a combination of immunologic, nutritional, and genetic characteristics; additional factors that influence susceptibility to cholera remain unidentified. C1 [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chowdhury, Fahima; Khan, Ashraful I.; Faruque, Abu S. G.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Logvinenko, Tanya] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jbharris@partners.org FU ICDDR; B: Centre for Health and Population Research [U01 AI058935, RO3 AI063079, R01 AI40725]; International Research Scientist Development Award [K01 TW07144, K01 TW07409]; Pediatric Scientist Development Program [K12 HD00850]; Fogarty International Clinical Research [D43 TW05572] FX This research was supported by ICDDR, B: Centre for Health and Population Research and by the following grants: U01 AI058935 ( S. B. C.); RO3 AI063079 (FQ); R01 AI40725 (E.T.R.); International Research Scientist Development Award K01 TW07144 (R.C.L.); Pediatric Scientist Development Program K12 HD00850 (J.B.H.); International Research Scientist Development Award K01 TW07409 (J.B.H.), and Fogarty International Clinical Research Scholars Program D43 TW05572 (A.I.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 88 Z9 89 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2008 VL 2 IS 4 AR e221 DI 10.1371/journal.pntd.0000221 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 385IA UT WOS:000261806700015 PM 18398491 ER PT J AU Pollack, MH Jensen, JE Simon, NM Kaufinan, RE Renshaw, PF AF Pollack, Mark H. Jensen, J. Eric Simon, Naomi M. Kaufinan, Rebecca E. Renshaw, Perry F. TI High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: Response to treatment with levetiracetam SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE GABA; glutamate; levetiracetam; MRS; social anxiety ID ANTIEPILEPTIC DRUG LEVETIRACETAM; IN-VIVO; PANIC DISORDER; DORSOMEDIAL HYPOTHALAMUS; RESONANCE-SPECTROSCOPY; DEPRESSED-PATIENTS; HUMAN BRAIN; OPEN-LABEL; INHIBITION; PHENELZINE AB Objective: Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD). Methods: We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N = 10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam. Results: For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment. Conclusion: Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam. (C) 2007 Elsevier Inc. All fights reserved. C1 [Pollack, Mark H.; Simon, Naomi M.; Kaufinan, Rebecca E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jensen, J. Eric; Renshaw, Perry F.] Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. RP Pollack, MH (reprint author), Ctr Anxiety & Stress Disorders, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM mpollack@partners.org OI Sripada, Rebecca/0000-0002-2844-3458 NR 40 TC 48 Z9 52 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD APR 1 PY 2008 VL 32 IS 3 BP 739 EP 743 DI 10.1016/j.pnpbp.2007.11.023 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 284EV UT WOS:000254690300019 PM 18206286 ER PT J AU Salzer, MS Wick, LC Rogers, JA AF Salzer, Mark S. Wick, Lindsay C. Rogers, Joseph A. TI Familiarity with and use of accommodations and supports among postsecondary students with mental illnesses SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHIATRIC DISABILITIES; UNIVERSITY-STUDENTS; HIGHER-EDUCATION; PERCEPTIONS; EXPERIENCE; COLLEGE AB Objective: Many persons with serious mental illnesses are interested in pursuing postsecondary education and are doing so in increasing numbers. Accommodations can be essential, but limited research suggests that few formally seek accommodations, although increased efforts to heighten awareness may be changing this. The purpose of this study was to examine whether students with mental illnesses are increasingly aware of, and utilize, accommodations and academic supports and to identify the supports that are most used and perceived to be most helpful. Methods: A national Internet survey was conducted from July 2005 to July 2006, resulting in responses from 190 current and 318 former students with mental illnesses. Results: The study found modest but significant negative correlations between how long ago students left college and their familiarity with accommodations, their request for or receipt of accommodations, and their use of the Office for Students With Disabilities. These results were particularly noticeable when comparing current and former students. Moderate positive correlations that were significant were found between familiarity with accommodations, use of campus disability offices, and request for or receipt of accommodations. Conclusions: There is increased awareness and use of accommodations among students with mental illnesses, but it is also clear that most receive supports directly from instructors without going through the formal accommodations process. Encouraging students to utilize disability offices and greater attention to accommodation barriers may further increase support seeking. Supports that are most used and viewed as most helpful provide direction for service providers and campus personnel in their efforts to facilitate students' educational goals. C1 [Salzer, Mark S.] Univ Penn, Sch Med, Dept Psychiat, Ctr Mental Hlth Policy & Serv Res, Philadelphia, PA 19104 USA. [Salzer, Mark S.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet & Integrated Serv Network 4, Philadelphia, PA USA. [Rogers, Joseph A.] Mental Hlth Assoc Southeastern Penn, Philadelphia, PA USA. RP Salzer, MS (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Mental Hlth Policy & Serv Res, 3535 Market St,3rd Floor, Philadelphia, PA 19104 USA. EM mark.salzer@uphs.upenn.edu NR 25 TC 22 Z9 22 U1 3 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2008 VL 59 IS 4 BP 370 EP 375 DI 10.1176/appi.ps.59.4.370 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 282OW UT WOS:000254578100007 PM 18378834 ER PT J AU Satre, D Wolfe, W Eisendrath, S Weisner, C AF Satre, Derek Wolfe, William Eisendrath, Stuart Weisner, Constance TI Computerized screening for alcohol and drug use among adults seeking outpatient psychiatric services SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH; INTERVENTION; CONSUMPTION; DEPRESSION; DRINKING; IMPACT AB Objective: This study examined routine computerized screening for alcohol and drug use of men and women seeking outpatient psychiatric services ( excluding chemical dependency treatment) and prevalence based on electronic medical records of consecutive admissions. Methods: The sample of 422 patients, ages 18 - 91, completed a self- administered questionnaire. Measures included 30- day, one- year, and lifetime substance use and alcohol-related problems. Results: Seventy-five percent of patients completed electronic intakes during the study period. Prior- month alcohol use was reported by 90 men ( 70%) and 180 women ( 62%). Of these patients, heavy drinking ( five or more drinks on one occasion) was reported by 37 men ( 41%) and 41 women ( 23%). Prior-month cannabis use was reported by 17 men ( 13%) and 32 women ( 11%). Conclusions: Computerized intake systems that include alcohol and drug screening can be integrated into outpatient psychiatric settings. Heavy drinking and use of nonprescribed drugs are commonly reported, which provides an important intervention opportunity. C1 [Satre, Derek; Wolfe, William; Eisendrath, Stuart; Weisner, Constance] Univ Calif San Francisco, Depress Ctr, San Francisco, CA 94143 USA. [Satre, Derek; Wolfe, William; Eisendrath, Stuart; Weisner, Constance] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Satre, Derek; Weisner, Constance] Kaiser Permanente, Div Res, Oakland, CA USA. [Wolfe, William] San Francisco VA Med Ctr, San Francisco, CA USA. RP Satre, D (reprint author), Univ Calif San Francisco, Depress Ctr, 401 Parnassus Ave,Box 0984, San Francisco, CA 94143 USA. EM dereks@lppi.ucsf.edu FU NIAAA NIH HHS [K23 AA015411, K23-AA015411]; NIDA NIH HHS [P50 DA009253, R37-DA10572, P50-DA09253, R37 DA010572] NR 16 TC 13 Z9 13 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2008 VL 59 IS 4 BP 441 EP 444 DI 10.1176/appi.ps.59.4.441 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 282OW UT WOS:000254578100019 PM 18378846 ER PT J AU Rasmussen, DD Crites, NJ Burke, BL AF Rasmussen, Dennis D. Crites, Norman J. Burke, Brianna L. TI Acoustic startle amplitude predicts vulnerability to develop post-traumatic stress hyper-responsivity and associated plasma corticosterone changes in rats SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; trauma; startle; corticosterone; vulnerability; risk factors ID CORTICOTROPIN-RELEASING-FACTOR; FEAR-POTENTIATED STARTLE; LIGHT-ENHANCED STARTLE; STRIA TERMINALIS; ANIMAL-MODEL; BED NUCLEUS; SITUATIONAL REMINDERS; HPA AXIS; DISORDER; ANXIETY AB Following exposure to trauma, a vulnerable sub-population of individuals develops post-traumatic stress disorder (PTSD) with characteristic persistent autonomic hyper-responsivity, associated increased startle response, and commonly altered hypothalamopituitary-adrenal regulation. A goal of this investigation was to identify a predictive marker for this vulnerability. Previous investigators have developed a model for PTSD in which male mice were exposed to a single brief episode of inescapable footshock followed by 1-min contextual reminders of this trauma at weekly intervals for 6 weeks. Exposure to these reminders induced a progressive and persistent increase in the amplitude of acoustic startle consistent with the persistently increased acoustic startle of individuals exhibiting PTSD. We adapted this model to adult male Wistar rats, with added characterization of initial (pre-trauma) startle response. After one episode of inescapable footshock (10s, 2mA) or control treatment followed by six weekly 1-min contextual reminders, acoustic startle was re-tested. Data were analyzed after dividing rats within each treatment into LOW vs MID vs HIGH (33% in each group) pre-treatment startle responders. Rats which exhibited pre-treatment LOW- and MID-range acoustic startle responses did not develop increased acoustic startle responses following subsequent traumatic stress+reminders ([TS+R]) treatment. However, rats which exhibited HIGH pre-treatment startle responses exhibited further significant (p<0.01) [TS+R]induced persistent enhancement of this already elevated startle response. Furthermore, rats exhibiting HIGH pre-treatment startle responses were also the only subgroup which exhibited increased basal plasma corticosterone levels following [TS+R] treatment. These results suggest that initial pre-stress acoustic startle response can identify subgroups of rats which are predisposed to, or resistant to, developing a PTSD-like syndrome following subsequent trauma. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, Seattle, WA 98108 USA. [Rasmussen, Dennis D.; Crites, Norman J.; Burke, Brianna L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU NIAAA NIH HHS [R01 AA010567, AA013881, AA10567, R01 AA010567-09, R01 AA013881, R01 AA013881-04] NR 40 TC 24 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2008 VL 33 IS 3 BP 282 EP 291 DI 10.1016/j.psyneuen.2007.11.010 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 282LD UT WOS:000254568400003 PM 18164825 ER PT J AU Primack, BA Land, SR Fine, MJ AF Primack, Brian A. Land, Stephanie R. Fine, Michael J. TI Adolescent smoking and volume of exposure to various forms of media SO PUBLIC HEALTH LA English DT Article DE tobacco; smoking prevention; adolescent health; mass media; television; films; music; school health ID TOBACCO INDUSTRY; MUSIC VIDEOS; ALCOHOL-USE; TELEVISION; INITIATION; OBESITY; PROMOTION; CHILDREN; CIGARETTES; MOVIES AB Objective: To assess the association between adolescent smoking and volume Tobacco; of exposure to various forms of media after controlling for multiple relevant covariates. Methods: A survey of all adolescents at a large suburban high school assessed: (1) current smoking and susceptibility to future smoking; (2) volume of exposure to various media; and (3) covariates related to smoking. Multivariate logistic regression models assessed relationships between each of the independent variables (media exposures) and the two smoking outcomes after controlling for covariates. Results: Of the 1111 respondents, 11% (n = 211) reported current smoking. Forty percent (n = 342) of the non-smokers (n = 922) were susceptible to future smoking. Students reported exposure to an average of 8.6 (standard deviation 5.1) h of media daily, including 2.6 h of music. Those with high exposure to films and music were more Likely to be smokers (P-trend = 0.036 and P-trend<0.001, respectively), and those with high exposure to books were less likely to be smokers (P-trend<0.001). After controlling for all relevant covariates, those with high exposure to music had greater odds of being smokers than those with low exposure [odds ratio (OR) 1.90, 95% confidence intervals (CI) 1.10-3.30], and those with high exposure to books had lower odds of being current smokers (OR 0.55, 95% CI 0.33-0.94). Conclusion: Exposure to films and music are associated with smoking, but only the relationship between music exposure and smoking persists after rigorous covariate control. Exposure to books is associated with tower odds of smoking. (C) 2008 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. C1 [Primack, Brian A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Primack, Brian A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Land, Stephanie R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Div Adolescent Med, Pittsburgh, PA 15213 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, 230 McKee Pl Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, 1K07-CA114315, K07 CA114315-02]; NIAID NIH HHS [5K24-AI01769, K24 AI001769] NR 37 TC 12 Z9 12 U1 1 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD APR PY 2008 VL 122 IS 4 BP 379 EP 389 DI 10.1016/j.puhe.2007.07.022 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286BA UT WOS:000254819000007 PM 18206196 ER PT J AU Thrall, JH AF Thrall, James H. TI Globalization of health care SO RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 14 Fruit St,MZ-FND 216,Box 9657, Boston, MA 02114 USA. EM jthrall@partners.org NR 17 TC 2 Z9 2 U1 1 U2 1 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 APR PY 2008 VL 247 IS 1 BP 3 EP 7 DI 10.1148/radiol.2471072134 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 279MF UT WOS:000254358600002 PM 18372459 ER PT J AU Nieman, K Shapiro, MD Ferencik, M Nomura, CH Abbara, S Hoffmann, U Gold, HK Jang, IK Brady, TJ Cury, RC AF Nieman, Koen Shapiro, Michael D. Ferencik, Maros Nomura, Cesar H. Abbara, Suhny Hoffmann, Udo Gold, Herman K. Jang, Ik-Kyung Brady, Thomas J. Cury, Ricardo C. TI Reperfused myocardial infarction: Contrast-enhanced 64-section CT in comparison to MR imaging SO RADIOLOGY LA English DT Article ID LEFT-VENTRICULAR FUNCTION; MULTIDETECTOR COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; MICROVASCULAR OBSTRUCTION; SUCCESSFUL THROMBOLYSIS; CORONARY-ANGIOGRAPHY; DIAGNOSTIC-ACCURACY; TIME-COURSE; ROW CT; PREDICTION AB Purpose: To prospectively compare 64-section multidetector computed tomography (CT) and cardiac magnetic resonance (MR) imaging for the early assessment of myocardial enhancement and infarct size after acute reperfused myocardial infarction (MI). Materials and Methods: The study was HIPAA compliant and was approved by the institutional review board. All participants gave written informed consent. Twenty-one patients (18 men; mean age, 60 years +/- 13 [standard deviation]) were examined with 64-section multidetector CT and cardiac MR imaging 5 days or fewer after a first reperfused MI. Multidetector CT was performed during the first pass of contrast material to assess myocardial perfusion and detect microvascular obstruction (no reflow). In 15 patients, a second scan was performed 7 minutes later to assess total infarct size by using delayed hyperenhancement. Early hypoenhancement and delayed hyperenhancement were compared between multidetector CT and cardiac MR imaging with Pearson correlation coefficient and Bland-Altman analysis. Results: Early hypoenhancement was recognized on all multidetector CT and cardiac MR images. Delayed hyperenhancement was observed with cardiac MR imaging at all examinations and with multidetector CT at 11 of 15 examinations. While signal intensity differences between hypoperfused and normal myocardium were comparable for first-pass multidetector CT and cardiac MR imaging, cardiac MR imaging had a far better contrast-to-noise ratio (CNR) for delayed acquisitions than did CT (P < .001). Hypoenhanced areas (as a percentage of left ventricular mass) at first-pass multidetector CT (11% +/- 6) correlated well with those at first-pass cardiac MR imaging (7% +/- 4, R-2 = 0.72). Delayed-enhancement multidetector CT (13% +/- 9) correlated well with delayed-enhancement cardiac MR imaging (15% +/- 7, R-2 = 0.55). Quantification of delayed hypoenhancement (n = 12) had very good correlation between multidetector CT (4% +/- 4) and cardiac MR imaging (3% +/- 2) (R-2 +/- 0.85). Conclusion: Early and late hypoenhancement showed good CNR and correlated well between multidetector CT and cardiac MR imaging. (c) RSNA, 2008. C1 [Nieman, Koen; Shapiro, Michael D.; Ferencik, Maros; Nomura, Cesar H.; Abbara, Suhny; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, MRI PET CT Program, Boston, MA 02114 USA. [Gold, Herman K.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gold, Herman K.; Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nieman, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, MRI PET CT Program, 165 Cambridge St, Boston, MA 02114 USA. EM koennieman@hotmail.com RI Nomura, Cesar/H-1636-2012 NR 36 TC 108 Z9 114 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2008 VL 247 IS 1 BP 49 EP 56 DI 10.1148/radiol.2471070332 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 279MF UT WOS:000254358600007 PM 18372464 ER PT J AU Drzymala, RE Wasserman, TH Won, M Shaw, E Cmelak, AJ Loeffler, J Souhami, L AF Drzymala, R. E. Wasserman, T. H. Won, M. Shaw, E. Cmelak, A. J. Loeffler, J. Souhami, L. CA Radiation Therapy Oncology Grp TI Phase I-B trial of the radiosensitizer: Etanidazole (SR-2508) with radiosurgery for the treatment of recurrent previously irradiated primary brain tumors or brain metastases (RTOG Study 95-02) SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE etanidazole; SR-2508; radiosurgery; brain tumors ID THERAPY ONCOLOGY GROUP; HIGH-GRADE GLIOMAS; RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; MOTEXAFIN GADOLINIUM; RANDOMIZED-TRIAL; CLINICAL-TRIALS; FINAL REPORT AB RTOG 95-02 assessed patient tolerance to hypoxic cell radiosensitizer, etanidazole (SR-2508), combined with radiosurgery. Patients had primary or metastatic brain tumors and previously localized or whole brain irradiation. The toxicity is reported in three groups of patients according to the tumor size. Etanidazole doses of 12 g/m(2) combined with radiosurgery were well tolerated. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Drzymala, R. E.; Wasserman, T. H.] Washington Univ, Med Ctr, St Louis, MO USA. [Won, M.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Shaw, E.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Cmelak, A. J.] Vanderbilt Univ, Nashville, TN USA. [Loeffler, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Souhami, L.] McGill Univ, Montreal, PQ, Canada. RP Drzymala, RE (reprint author), WUSM, Siteman Canc Ctr, Dept Radiat Oncol, 4921 Pkwy Pl, St Louis, MO 63110 USA. EM rdrzymala@radonc.wustl.edu NR 23 TC 6 Z9 6 U1 0 U2 1 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 APR PY 2008 VL 87 IS 1 BP 89 EP 92 DI 10.1016/j.radonc.2008.02.006 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 300TK UT WOS:000255847900014 PM 18342381 ER PT J AU Hirsch, AE Medich, DC Rosenstein, BS Martel, CB Hirsch, JA AF Hirsch, Ariel E. Medich, David C. Rosenstein, Barry S. Martel, Christopher B. Hirsch, Joshua A. TI Radioisotopes and vertebral augmentation: Dosimetric analysis of a novel approach for the treatment of malignant compression fractures SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE vertebral compression fracture; isotope; dosimetry; Monte Carlo; vertebroplasty ID METASTATIC BONE-DISEASE; PERCUTANEOUS VERTEBROPLASTY; PATHOLOGICAL FRACTURES; BREAST-CANCER; PATHOPHYSIOLOGY; COMPLICATIONS; KYPHOPLASTY; THERAPY AB Purpose: Vertebral compression fractures (VCFs), a major cause of morbidity and debilitating pain, often results from secondary tumor metastases to the skeleton. Vertebral augmentation is a palliative technique developed to treat VCFs and involves the injection of polymethyl methacrylate (PMMA) to augment the fractured vertebral body. The authors investigate the feasibility of radionuclide therapy coupled with vertebral augmentation to treat both the tumor metastases and VCFs. Six therapeutic radioisotopes, uniformly mixed in a PMMA bolus, were investigated for their dosimetric properties. Methods and materials: The MCNP5 Monte Carlo computer code was used to characterize the therapeutic dosimetric distribution within a cortical bone phantom for a 1 mm radial bolus of isotope-infused PMMA. Based on these data, the minimum activity required for a therapeutic treatment was calculated. Results: The dosimetry from beta emitting Y-90, P-32, and Ho-166 decreased to 10% of its maximum therapeutic dose (R(10%)) after traveling 1.20 mm, 1.03 mm, and 0.97 mm, respectively, through cortical bone. Low photon energy 1-125 had a slightly larger calculated R(10%) of 1.32 mm. Although F-18 and Tc-99m exhibited a more uniform distribution (R(10%) = 1.72 mm and 1.94 mm, respectively), the lower dosimetric gradients resulted in significantly greater therapeutic implant activities relative to the other isotopes studied in this report. Conclusions: Radionuclide therapy coupled with vertebral augmentation is shown to be a feasible technique for the treatment of secondary skeletal metastases and its resulting side effects. Future studies will include a full clinical investigation to determine optimal treatment isotope(s). (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Hirsch, Ariel E.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Hirsch, Ariel E.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Medich, David C.] Univ Massachusetts Loweli, Radiat Lab, Loweli, MA USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. [Rosenstein, Barry S.] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA. [Martel, Christopher B.] Boston Univ, Med Ctr, Dept Radiat Protect, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hirsch, AE (reprint author), Boston Univ, Med Ctr, Dept Radiat Oncol, 830 Harrison Ave,Moakley Bldg,Lower Level, Boston, MA 02118 USA. EM ariel.hirsch@bmc.org; David_Medich@uml.edu; barry.rosenstein@mssm.edu; cbmartel@bu.edu; jahirsch@partners.org RI Rosenstein, Barry/A-7420-2009; Medich, David/B-6006-2013 NR 33 TC 15 Z9 16 U1 0 U2 2 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 APR PY 2008 VL 87 IS 1 BP 119 EP 126 DI 10.1016/j.radonc.2008.01.010 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 300TK UT WOS:000255847900019 PM 18261814 ER PT J AU Williams, DL Goldstein, G Kojkowski, N Minshew, NJ AF Williams, Diane L. Goldstein, Gerald Kojkowski, Nicole Minshew, Nancy J. TI Do individuals with high functioning autism have the IQ profile associated with nonverbal learning disability? SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Nonverbal learning disability; Asperger syndrome; Wechsler intelligence scales ID PHONOLOGICAL PROCESSING DISABILITIES; DIAGNOSTIC OBSERVATION SCHEDULE; ASPERGER-SYNDROME; RIGHT-HEMISPHERE; CHILDREN; CLASSIFICATION; INTERVIEW; LANGUAGE; VALIDITY; SPECTRUM AB Previously researchers have noted a high level of occurrence of the IQ profile associated with nonverbal learning disability (NLD) in Asperger syndrome (ASP) but not in high functioning autism (HFA). We examined the IQ profile scores of a large sample of children (n = 69) and adults (n = 77) with HFA. stringently diagnosed according to ADOS, ADI-R. and DSM-IV criteria. and a corresponding sample of typical child (it = 72) and adult controls (it = 107). At least one of the three primary components of the Wechsler pattern seen in NLD were found in 17-26% of the children and 20-32% of the adults with HFA. All three components occurred in slightly more than 5% of the children and adults with autism. Overall, the VIQ > PIQ profile seen in NLD occurred in 18% of the sample of individuals stringently diagnosed with HFA. Therefore, obtaining this IQ profile is not a valid clinical discriminator between NLD and HFA. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Williams, Diane L.] Duquesne Univ, Rangos Sch Hlth Sci, Dept Speech Language Pathol, Pittsburgh, PA 15282 USA. [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. RP Williams, DL (reprint author), Duquesne Univ, Rangos Sch Hlth Sci, Dept Speech Language Pathol, 600 Forbes Ave, Pittsburgh, PA 15282 USA. EM williamsd2139@duq.edu RI Williams, Diane/B-4128-2017 FU NICHD NIH HHS [P50 HD055748, U19 HD035469-08, U19 HD035469-10, U19 HD035469, U19 HD035469-07, U19 HD035469-06, U19 HD035469-09]; NIDCD NIH HHS [K23 DC006691, K23 DC006691-01, K23 DC006691-04] NR 37 TC 27 Z9 29 U1 3 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD APR-JUN PY 2008 VL 2 IS 2 BP 353 EP 361 DI 10.1016/j.rasd.2007.08.005 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 408DJ UT WOS:000263413800014 PM 18516234 ER PT J AU Siegel, RE AF Siegel, Robert E. TI Emerging gram-negative antibiotic resistance: Daunting challenges, declining sensitivities, and dire consequences SO RESPIRATORY CARE LA English DT Review DE antibiotics; multidrug resistance; Gram-negative pathogens; Pseudomonas aeruginosa; Acinetobacter baumannii; extended-spectrum beta lactamases; carbapenems; de-escalation ID VENTILATOR-ASSOCIATED PNEUMONIA; SPECTRUM BETA-LACTAMASES; COMMUNITY-ACQUIRED PNEUMONIA; FEBRILE NEUTROPENIC PATIENTS; III SECRETION SYSTEM; CARE-UNIT PATIENTS; PSEUDOMONAS-AERUGINOSA; ACINETOBACTER-BAUMANNII; KLEBSIELLA-PNEUMONIAE; NEW-YORK AB Emerging antibiotic resistance has created a major public health dilemma, compounded by a dearth of new antibiotic options. Multidrug-resistant Gram-negative organisms have received less attention than Gram-positive threats, such as methicillin-resistant Staphylococcus aureus, but are just as menacing. Pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii employ a variety of resistance mechanisms and are associated with dangerous nosocomial outbreaks. In some cases these pathogens have expressed resistance to all clinically available compounds. The emergence of extended-spectrum beta-lactamase-producing organisms in the community has raised alarm. Furthermore, the carbapenems, currently the most successful class of antibiotics, are showing signs of vulnerability. While the search for new antibiotic options continues, there is urgent need to employ strategies that will slow the development of resistance to the current armamentarium, such as avoiding prolonged antibiotic use or tinder-dosing, using pharmacokinetic and pharmacodynamic principles to choose dosing regimens, and encouraging early and aggressive empirical therapy, followed by de-escalation and narrowing the antimicrobial spectrum when culture results become available. C1 [Siegel, Robert E.] James J Peters Vet Affaors Med Ctr, Dept Pulm & Crit Care Med, Bronx, NY 10468 USA. [Siegel, Robert E.] Mt Sinai Sch Med, Bronx, NY USA. RP Siegel, RE (reprint author), James J Peters Vet Affaors Med Ctr, Dept Pulm & Crit Care Med, 130 Kingsbridge Rd, Bronx, NY 10468 USA. EM robert.siegel@va.gov NR 62 TC 55 Z9 56 U1 1 U2 4 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2008 VL 53 IS 4 BP 471 EP 479 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285DW UT WOS:000254758500009 PM 18364060 ER PT J AU Goldberger, ZD AF Goldberger, Zachary D. TI Severe hypothermia with Osborn waves in diabetic ketoacidosis SO RESPIRATORY CARE LA English DT Article ID CLINICAL-SIGNIFICANCE; LIPASE AB Diabetic ketoacidosis causes substantial morbidity and mortality.(1) Though the management of acute diabetic ketoacidosis centers on correcting hyperglycemia and electrolyte abnormalities, other important metabolic derangements may be seen. Specifically, hypothermia may be both a cause and consequence of diabetic ketoacidosis, and the severity of the hypothermia correlates with the severity of the illness. The case presented below highlights a presentation of severe diabetic ketoacidosis associated with hypothermia, which caused distinctive changes (Osborn waves) on the electrocardiogram (ECG). In the setting of diabetic ketoacidosis the recognition of ECG changes characteristic of hypothermia will help guide management and avoid the misdiagnosis of an ST-segment elevation myocardial infarction. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Internal Med, Seattle, WA USA. RP Goldberger, ZD (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Internal Med, 1660 S Columbian Way,Box S-111-CHF, Seattle, WA USA. EM zgoldber@u.washington.edu NR 12 TC 5 Z9 5 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2008 VL 53 IS 4 BP 500 EP 502 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 285DW UT WOS:000254758500012 PM 18364063 ER PT J AU Tashkin, DP Littner, M Andrews, CP Tomlinson, L Rinehart, M Denis-Mize, K AF Tashkin, Donald P. Littner, Michael Andrews, Charles P. Tomlinson, LaTanya Rinehart, Mike Denis-Mize, Kimberly TI Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: A placebo-controlled trial SO RESPIRATORY MEDICINE LA English DT Article DE formoterol; tiotropium; COPD; long-acting; beta(2)-agonist; nebulization ID OBSTRUCTIVE PULMONARY-DISEASE; STABLE COPD; MULTICENTER TRIAL; DRY POWDER; COMBINATION; DYSPNEA; SAFETY; EFFICACY; HYPERINFLATION; THEOPHYLLINE AB Adding a long-acting beta(2)-agonist (LABA) by dry powder inhaler (DPI) to tiotropium provides significantly increased and sustained bronchodilation in chronic obstructive pulmonary disease (COPD) patients over either product alone. To demonstrate similar benefits with a nebulized LABA, a placebo-controlled trial was conducted to evaluate the efficacy and safety of formoterol fumarate inhalation solution in subjects receiving tiotropium as a maintenance treatment for COPD. After a 7-14-day screening period using tiotropium 18 mu g once daily, subjects with diagnosed COPD (>= 25% to <65% predicted FEV1) were randomized to receive 20 mu g formoterol fumarate inhalation solution twice daily for nebulization plus tiotropium (FFIS/TIO) or nebulized placebo twice daily plus tiotropium (PLA/TIO) for 6 weeks. Efficacy was assessed with spirometry at each visit (Day 1, Week 1, 3, 6), the transition dyspnea index (TDI), and St. George's Respiratory Questionnaire (SGRQ). Baseline characteristics were comparable, including mean FEV1% predicted. At Week 6, FEV1 AUC(0-3) was 1.52L for FFIS/TIO-treated subjects vs. 1.34L for PLA/TIO-treated subjects (p<0.0001). The mean TDI scores in the FFIS/TIO and PLA/TIO groups were 2.30 and 0.16, respectively (p = 0.0002). SGRQ did not change significantly with 6 weeks treatment, with the exception of FFIS/TIO improvements in symptom score vs. PLA/TIO (p = 0.04). More PLA/TIO- than. FFIS/TIO-treated subjects experienced AEs (39.7% vs. 22.9%), COPD exacerbations (7.9% vs. 4.5%), and serious AEs (3.2% vs. 1.5%). C1 [Tashkin, Donald P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Littner, Michael] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. [Andrews, Charles P.] Diagnost Res Grp, San Antonio, TX 78229 USA. [Tomlinson, LaTanya; Rinehart, Mike; Denis-Mize, Kimberly] Dey LP, Napa, CA 94558 USA. RP Tashkin, DP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 10833 LeConte Ave,CHS 32-176, Los Angeles, CA 90095 USA. EM dtashkin@mednet.ucla.edu OI Andrews, Charles/0000-0002-8944-8404 NR 34 TC 60 Z9 65 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD APR PY 2008 VL 102 IS 4 BP 479 EP 487 DI 10.1016/j.rmed.2007.12.019 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 278QV UT WOS:000254302300001 PM 18258423 ER PT J AU Dasgupta, B Durez, P Kay, J Matteson, EL Nash, P Hall, S Hsia, EC Chiruvolu, P Han, J Rahman, M AF Dasgupta, B. Durez, P. Kay, J. Matteson, E. L. Nash, P. Hall, S. Hsia, E. C. Chiruvolu, P. Han, J. Rahman, M. CA CNTO 148 Study Grp TI Improvement in das28 response through 1-yr of golimumab treatment in pts with active RA despite treatment with MTX: A randomized, double blind, placebo-controlled, dose-ranging trial SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-Rheumatology/Spring Meeting of British Health Professional in Rheumatology CY APR 22-25, 2008 CL Liverpool, ENGLAND SP British Soc Rheumatol C1 [Dasgupta, B.] Southend Hosp, Westcliff S E, England. [Durez, P.] Clin Univ St Luc, B-1200 Brussels, Belgium. [Kay, J.] Mass Gen Hosp, Boston, MA USA. [Matteson, E. L.] Mayo Coll Med, Rochester, MN USA. [Nash, P.] Sixth Ave Specialist Ctr, Cotton Tree, Qld, Australia. [Hall, S.] Cabrini Med Ctr, Melbourne, Vic, Australia. [Hsia, E. C.; Chiruvolu, P.; Han, J.; Rahman, M.] Centocor R&D Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2008 VL 47 SU 2 BP II50 EP II51 PG 2 WC Rheumatology SC Rheumatology GA 284BT UT WOS:000254680900170 ER PT J AU Hazlett, EA Buchsbaum, MS Haznedar, MM Newmark, R Goldstein, KE Zelmanova, Y Glanton, CF Torosjan, Y New, AS Lo, JN Mitropoulou, V Siever, LJ AF Hazlett, Erin A. Buchsbaum, Monte S. Haznedar, M. Mehmet Newmark, Randall Goldstein, Kim E. Zelmanova, Yuliya Glanton, Cathryn F. Torosjan, Yuliya New, Antonia S. Lo, Jennifer N. Mitropoulou, Vivian Siever, Larry J. TI Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MRI; schizophrenia; schizotypal personality disorder; frontal lobe volume; temporal lobe volume; cingulate gyrus; negative symptoms; gray matter volume; white matter volume ID CINGULATE GYRUS VOLUME; PERSONALITY-DISORDER; VULNERABILITY INDICATOR; INDIVIDUAL-DIFFERENCES; PARAHIPPOCAMPAL GYRUS; SPECTRUM DISORDERS; VENTRICULAR VOLUME; GLUCOSE-METABOLISM; MRI ABNORMALITIES; PLANUM TEMPORALE AB Magnetic resonance imaging (MRI) studies have revealed fronto-temporal cortical gray matter volume reductions in schizophrenia. However, to date studies have not examined whether age- and sex-matched unmedicated schizotypal personality disorder (SPD) patients share some or all of the structural brain-imaging characteristics of schizophrenia patients. We examined cortical gray/white matter volumes in a large sample of unmedicated schizophrenia-spectrum patients (n = 79 SPD, n = 57 schizophrenia) and 148 healthy controls. MRI images were reoriented to standard position parallel to the anterior-posterior commissure line, segmented into gray and white matter tissue types, and assigned to Brodmann areas (BAs) using a postmortem-histological atlas. Group differences in regional volume of gray and white matter in the BAs were examined with MANOVA. Schizophrenia patients had significantly reduced gray matter volume widely across the cortex but more marked in frontal and temporal lobes. SPD patients had reductions in the same regions but only about half that observed in schizophrenia and sparing in key regions including BA10. In schizophrenia, greater fronto-temporal volume loss was associated with greater negative symptom severity and in SPD, greater interpersonal and cognitive impairment. Overall, our findings suggest that increased prefrontal volume in BA10 and sparing of volume loss in temporal cortex (BAs 22 and 20) may be a protective factor in SPD which reduces vulnerability to psychosis. Published by Elsevier B.V. C1 [Hazlett, Erin A.; Buchsbaum, Monte S.; Haznedar, M. Mehmet; Newmark, Randall; Goldstein, Kim E.; Zelmanova, Yuliya; Glanton, Cathryn F.; Torosjan, Yuliya; New, Antonia S.; Lo, Jennifer N.; Mitropoulou, Vivian; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [New, Antonia S.; Siever, Larry J.] Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. EM erin.hazlett@mssm.edu FU NCRR NIH HHS [M01 RR000071, M01-RR00071]; NIMH NIH HHS [R01 MH040071-06A2, MH073911, MH40071, MH56489, MH56606, MH60023, R01 MH040071, R01 MH056489, R01 MH056489-02, R01 MH056606, R01 MH056606-03, R01 MH060023, R01 MH060023-05, R01 MH065554, R01 MH073911, R01 MH073911-02] NR 51 TC 64 Z9 65 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2008 VL 101 IS 1-3 BP 111 EP 123 DI 10.1016/j.schres.2007.12.472 PG 13 WC Psychiatry SC Psychiatry GA 305XX UT WOS:000256212200013 PM 18272348 ER PT J AU Meyer, JM Davis, VG Goff, DC McEvoy, JP Nasrallah, HA Davis, SM Rosenheck, RA Daumit, GL Hsiao, J Swartz, MS Stroup, TS Lieberman, JA AF Meyer, Jonathan M. Davis, Vicki G. Goff, Donald C. McEvoy, Joseph P. Nasrallah, Henry A. Davis, Sonia M. Rosenheck, Robert A. Daumit, Gail L. Hsiao, John Swartz, Marvin S. Stroup, T. Scott Lieberman, Jeffrey A. TI Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: Prospective data from phase 1 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE antipsychotic; schizophrenia; metabolic syndrome; lipids; HDL; triglycerides; waist circumference; central adiposity ID INTERNATIONAL-DIABETES-FEDERATION; TREATMENT PANEL-III; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; ATYPICAL ANTIPSYCHOTICS; FOLLOW-UP; RISK; GLUCOSE AB Background: The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase I of the CATIE Schizophrenia Trial. Methods: The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase I participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. Results: At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n = 660). Among all subjects whose MS status could be determined at 3 months (n = 660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p = .001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP. Conclusions: This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment. (C) 2008 Elsevier B.V. All rights reserved. C1 [Meyer, Jonathan M.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Meyer, Jonathan M.] VA San Diego Healthcare Syst, San Diego, CA USA. [Davis, Vicki G.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Bank Amer Ctr, Chapel Hill, NC 27514 USA. [Goff, Donald C.] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. [Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. [McEvoy, Joseph P.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [McEvoy, Joseph P.] John Umstead Hosp, Butner, NC 27509 USA. [Nasrallah, Henry A.] Univ Cincinnati, Cincinnati, OH 45267 USA. [Davis, Sonia M.] Quintiles Inc, Morrisville, NC 27560 USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. [Rosenheck, Robert A.] VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr, West Haven, CT 06516 USA. [Daumit, Gail L.] Johns Hopkins Med Inst, Baltimore, MD 21287 USA. [Hsiao, John] NIMH, Adult Psychopharmacol Intervent Program, Bethesda, MD 20892 USA. [Swartz, Marvin S.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Stroup, T. Scott] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, Inst Psychiat, New York, NY 10032 USA. RP Meyer, JM (reprint author), San Diego VAMC, 3350 La Jolla Village Dr 116A, San Diego, CA 92161 USA. EM jmmeyer@ucsd.edu; Vicki.Davis@mail.cscc.unc.edu; goff@psych.mgh.harvard.edu; jpmcevoy@duke.edu; NASRALHA@ucmail.uc.edu; sonia.davis@quintiles.com; robert.rosenheck@yale.edu; gdaumit@jhmi.edu; jh23f@nih.gov; swart001@mc.duke.edu; scott_stroup@med.unc.edu; JL2616@columbia.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NCRR NIH HHS [M01 RR000046-441041, M01 RR000046, M01 RR000046-451041]; NIMH NIH HHS [N01MH90001] NR 48 TC 134 Z9 137 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2008 VL 101 IS 1-3 BP 273 EP 286 DI 10.1016/j.schres.2007.12.487 PG 14 WC Psychiatry SC Psychiatry GA 305XX UT WOS:000256212200031 PM 18258416 ER PT J AU Wang, ZH Deisboeck, TS AF Wang, Zhihui Deisboeck, Thomas S. TI Computational modeling of brain tumors: discrete, continuum or hybrid? SO SCIENTIFIC MODELING AND SIMULATIONS LA English DT Article DE Brain tumor; Agent-based model; Cellular automata; Continuum; Multi-scale ID IN-VIVO; GLIOBLASTOMA-MULTIFORME; MATHEMATICAL-MODEL; SIMULATION-MODEL; GROWTH DYNAMICS; CELL-MIGRATION; GLIOMA GROWTH; MULTICELLULAR PATTERNS; NONLINEAR SIMULATION; INDUCED ANGIOGENESIS AB In spite of all efforts, patients diagnosed with highly malignant brain tumors ( gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed. C1 [Wang, Zhihui; Deisboeck, Thomas S.] Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. RP Wang, ZH (reprint author), Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NIH [CA 113004]; Harvard-MIT ( HST) FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT ( HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. We apologize to all colleagues whose works we could not cite due to space limitations. NR 73 TC 29 Z9 29 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1874-8554 J9 SCI MODEL SIMUL JI Sci. Model. Simul. PD APR PY 2008 VL 15 IS 1-3 BP 381 EP 393 DI 10.1007/s10820-008-9094-0 PG 13 WC Materials Science, Multidisciplinary; Physics, Condensed Matter SC Materials Science; Physics GA 405CX UT WOS:000263201100020 ER PT J AU Kanellopoulou, C Monticelli, S AF Kanellopoulou, Chryssa Monticelli, Silvia TI A role for microRNAs in the development of the immune system and in the pathogenesis of cancer SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE microRNA; hematopoiesis; cancer; targets; proliferation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; DOUBLE-STRANDED-RNA; GENE-EXPRESSION; MESSENGER-RNA; MICROPROCESSOR COMPLEX; REDUCED EXPRESSION; PROTEIN-SYNTHESIS; ENZYME DICER; C-ELEGANS AB MicroRNAs are a growing class of endogenous small non-coding RNAs that regulate gene expression by binding to target messenger RNAs and inducing translational repression, cleavage or destabilization of the target. Because each miRNA potentially can regulate expression of a distinct set of genes, it is conceivable that the differential expression of different miRNAs might profoundly influence the repertoire of genes that are expressed during development, differentiation or disease. Here, we provide background on the biogenesis and function of miRNAs, and discuss how miRNA-mediated regulation can influence tumorigenesis as well as normal development and function of cells of the immune system. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Monticelli, Silvia] Inst Biomed Res, CH-6500 Bellinzona, Switzerland. [Kanellopoulou, Chryssa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Med, Boston, MA 02115 USA. RP Monticelli, S (reprint author), Inst Biomed Res, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. EM silvia.monticelli@irb.unisi.ch NR 117 TC 27 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 2008 VL 18 IS 2 BP 79 EP 88 DI 10.1016/j.semcancer.2008.01.002 PG 10 WC Oncology SC Oncology GA 289GH UT WOS:000255042500002 PM 18291671 ER PT J AU LaCasce, AS Freedman, AS AF LaCasce, Ann S. Freedman, Arnold S. TI Antibody and immunomodulatory agents in the treatment of indolent non-Hodgkin's lymphoma SO SEMINARS IN HEMATOLOGY LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; EVENT-FREE SURVIVAL; PHASE-I TRIAL; COMBINATION IMMUNOTHERAPY; FOLLICULAR LYMPHOMA; LOW-GRADE; B-CELLS; RITUXIMAB; INTERFERON-ALPHA-2A; INTERLEUKIN-12 AB Immunomodulatory agents, including cytokines, CpG oligonucleotides, and anti-idiotype vaccines have properties that suggest they have the ability to augment rituximab in the treatment of non-Hodgkin's lymphoma (NHL). Although several clinical trials have shown promising results, no randomized trials of reasonable size have been reported to date, limiting the ability to discern whether combinations of immunomodulatory agents with rituximab impact clinical outcome. Until such trials are mature, we do not recommend using these agents in combination outside of the research setting. C1 [LaCasce, Ann S.; Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP LaCasce, AS (reprint author), Dana Farber Canc Inst, 44 Binney St,D1B05, Boston, MA 02115 USA. EM Ann-LaCasce@dfci.harvard.edu RI Geyer, Susan/E-3112-2011 NR 41 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2008 VL 45 IS 2 BP 85 EP 89 DI 10.1053/j.seminhematol.2008.02.004 PG 5 WC Hematology SC Hematology GA 285UL UT WOS:000254801600004 PM 18381102 ER PT J AU Moloo, J Shapiro, MD Abbara, S AF Moloo, Jamaluddin Shapiro, Michael D. Abbara, Suhny TI Cardiac computed tomography: Technique and optimization of protocols SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CORONARY-ANGIOGRAPHY; CT; RECONSTRUCTION; ARTERIES C1 [Shapiro, Michael D.; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Moloo, Jamaluddin] Univ Colorado, Dept Med, Aurora, CO USA. [Moloo, Jamaluddin] Univ Colorado, Heart & Vasc Ctr, Aurora, CO USA. RP Abbara, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,GRB-290, Boston, MA 02114 USA. EM SAbbara@Partners.org NR 12 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD APR PY 2008 VL 43 IS 2 BP 90 EP 99 DI 10.1053/j.ro.2008.01.004 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276RR UT WOS:000254160400004 PM 18329520 ER PT J AU Abbara, S Soni, AV Cury, RC AF Abbara, Suhny Soni, Anand V. Cury, Ricardo C. TI Evaluation of cardiac function and valves by multidetector row computed tomography SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; CORONARY-ARTERY-DISEASE; VALVULAR HEART-DISEASE; MAGNETIC-RESONANCE; AORTIC-STENOSIS; MITRAL-VALVE; INITIAL-EXPERIENCE; CT SCANS; QUANTIFICATION C1 [Abbara, Suhny; Soni, Anand V.; Cury, Ricardo C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 165 Cambridge St,Sutie 400, Boston, MA 02114 USA. EM Sabbara@partners.org NR 58 TC 7 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD APR PY 2008 VL 43 IS 2 BP 145 EP 153 DI 10.1053/j.ro.2008.01.009 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 276RR UT WOS:000254160400009 PM 18329525 ER PT J AU Madan, V Brennan, FX Mann, GL Horball, AA Dunn, GA Ross, RJ Morrison, AR AF Madan, Vibha Brennan, Francis X. Mann, Graziella L. Horball, Apryle A. Dunn, Gregory A. Ross, Richard J. Morrison, Adrian R. TI Long-term effect of cued fear conditioning on REM sleep microarchitecture in rats SO SLEEP LA English DT Article DE anxiety; freezing; muscle twitches; fear conditioning; PTSD; REM sleep ID POSTTRAUMATIC-STRESS-DISORDER; CONTEXTUAL FEAR; BALB/CJ MICE; AMYGDALA; DISTURBANCE; NUCLEUS; PATTERN; MEMORY AB Study Objectives: To study long-term effects of conditioned fear on REM sleep (REMS) parameters in albino rats. Design: We have investigated disturbances in sleep architecture, including muscle twitch density as REMS phasic activity, and freezing behavior in wakefulness, upon reexposure to a conditioned stimulus (CS) on Day 1 and Day 14 postconditioning. Subjects: Male Sprague-Dawley rats prepared for polysomnographic recordings. Interventions: After baseline sleep recording, the animals in the experimental group received five pairings of a 5-sec tone, co-terminating with a 1-sec, 1 mA footshock. The control rats received similar numbers of tones and shocks, but explicitly unpaired. On postconditioning days, after reexposure to tones alone, sleep and freezing behavior were recorded. Measurements and Results: Conditioned fear significantly altered REMS microarchitecture (characterized as sequential-REMS -[seq-REMS: <= 3 min episode separation] and single-REMS [sin-REMS: >3 min episode separation]) on Day 14. The total amount and number of seq-REMS episodes decreased, while the total amount and number of sin-REMS episodes increased. Further, the CS induced significant increases in freezing and REMS myoclonic twitch density in the experimental group. Reexposure to the CS produced no alterations in controls. Conclusions: The results suggest that conditioned fear causes REMS alterations, including difficulty in initiating a REMS episode as indicated by the diminution in the number of seq-REMS episodes. Another finding, the increase in phasic activity, agrees with the inference from clinical investigations that retrieval of fearful memories can be associated with the long-term REMS disturbances characteristic of posttraumatic stress disorder. C1 [Madan, Vibha; Brennan, Francis X.; Mann, Graziella L.; Horball, Apryle A.; Dunn, Gregory A.; Ross, Richard J.; Morrison, Adrian R.] Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. [Brennan, Francis X.; Ross, Richard J.; Morrison, Adrian R.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Brennan, Francis X.; Ross, Richard J.] Vet Affairs Med Ctr, Philadelphia, PA USA. RP Morrison, AR (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, 3800 Spruce St, Philadelphia, PA 19104 USA. EM armsleep@vet.upenn.edu FU NIMH NIH HHS [R01-MH072897, R01 MH072897] NR 29 TC 18 Z9 18 U1 2 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2008 VL 31 IS 4 BP 497 EP 503 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 287SI UT WOS:000254936400009 PM 18457237 ER PT J AU Murphy, JM Burke, JD Monson, RR Horton, NJ Laird, NM Lesage, A Sobol, AM Leighton, AH AF Murphy, Jane M. Burke, Jack D., Jr. Monson, Richard R. Horton, Nicholas J. Laird, Nan M. Lesage, Alain Sobol, Arthur M. Leighton, Alexander H. TI Mortality associated with depression - A forty-year perspective from the Stirling county study SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE mortality; depression; cigarettes; alcoholism; time-trends ID EPIDEMIOLOGIC CATCHMENT-AREA; NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; FOLLOW-UP; GENERAL-POPULATION; MAJOR DEPRESSION; GENDER DIFFERENCES; ANXIETY DISORDERS; DSM-III; MENTAL-DISORDERS AB Background This report concerns long-term mortality risks associated with depression, and the potentially confounding factors of alcoholism and cigarette smoking, as experienced by a general population assessed at a baseline in 1952, followed for re-assessment of survivors in 1968, and for death by 1992. Methods Self-report and physician-report information was gathered in 1952 and again in 1968 about a sample of 1,079 adults. At the end of follow-up in 1992, the vital status of all subjects was known. Comorbidity among depression, alcoholism, and smoking was investigated. Cox regression models were employed to estimate hazard ratios (HRs) as indicators of mortality risk. Models including age, gender, and depression were fit for the complete sample at baseline as well as for re-assessed survivors. Models simultaneously controlling for the mortality risks associated with depression, alcoholism, and heavy smoking were fit for men. Results At the baseline in 1952, depression was somewhat more common among women than men (4% compared to 6%) but was found to carry a significant mortality risk only among men (HR 2.7, 95% CI 1.6-4.7). Based on re-assessments made in 1968, depression was associated with mortality risk among both men (HR 2.2, 95% CI 1.0-4.5) and women (HR 2.1, 95% CI 1.2-3.8). In 1952, more than 20% of men smoked cigarettes excessively and 8% abused alcohol, but very few of these groups of men were also depressed. In the original sample and also among the survivors, depression, alcoholism, and heavy smoking were separately associated with mortality among men. Depression and alcoholism carried a more immediate mortality risk while heavy smoking a more delayed one. Conclusions At the baseline of the Stirling County Study, the mortality risk associated with depression among men was not enhanced or explained by abuse of alcohol or nicotine, mainly because comorbidity was rare at that time. The longitudinal research of the study has pointed to a number of psychiatrically-relevant time-trends such as the fact that an association between depression and cigarette smoking did not appear until the 1990s. It is hypothesized that a similar trend may emerge over time regarding the comorbidity of depression and alcoholism. A trend reported here was that, while depressed women in the original sample did not carry a significant mortality risk, the surviving women who were depressed at the time of re-assessment exhibited a mortality risk that was as significant as that for men. Such information may provide a useful back-drop for future investigations. C1 [Murphy, Jane M.; Burke, Jack D., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Burke, Jack D., Jr.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. [Murphy, Jane M.; Monson, Richard R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Laird, Nan M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. [Horton, Nicholas J.] Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. [Lesage, Alain] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Lesage, Alain] Hop LH Lafontaine, Ctr Rech Fernand Seguin, Montreal, PQ, Canada. RP Murphy, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Room 215,5 Longfellow Pl, Boston, MA 02114 USA. EM murphy.jane@mgh.harvard.edu RI Burke, Jack/I-4440-2012; OI Burke, Jack/0000-0001-5868-1695; Horton, Nicholas/0000-0003-3332-4311 FU NIMH NIH HHS [R01-MH39576-21] NR 73 TC 27 Z9 27 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD APR PY 2008 VL 43 IS 8 BP 594 EP 601 DI 10.1007/s00127-008-0323-3 PG 8 WC Psychiatry SC Psychiatry GA 350OV UT WOS:000259363900002 PM 18327523 ER PT J AU Abel, GA Glinert, LH AF Abel, Gregory A. Glinert, Lewis H. TI Chemotherapy as language: Sound symbolism in cancer medication names SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE sound symbolism; psycholinguistics; oncology; marketing; cancer; chemotherapy; medications ID PHONETIC SYMBOLISM; DRUG AB The concept of sound symbolism proposes that even the tiniest sounds comprising a word may suggest the qualities of the object which that word represents. Cancer-related medication names, which are likely to be charged with emotional meaning for patients, might be expected to contain such sound-symbolic associations. We analyzed the sounds in the names of 60 frequently-used cancer-related medications, focusing on the medications' trade names as well as the names (trade or generic) commonly used in the clinic. We assessed the frequency of common voiced consonants (/b/, /d/, /g/, /v/, /z/; thought to be associated with slowness and heaviness) and voiceless consonants (/p/, /t/, /k/, /f/, /s/; thought to be associated with fastness and lightness), and compared theta to what would be expected in standard American English using a reference dataset. A Fisher's exact test for independence showed the chemotherapy consonantal frequencies to be significantly different from standard English (p = 0.009 for trade; p < 0.001 for "common usage"). For the trade names, the majority of the voiceless consonants were significantly increased compared to standard English; this effect was more pronounced with the "common usage" names (for the group, O/E = 1.62; 95% CI [1.37, 1.89]). Hormonal and targeted therapy trade names showed the greatest frequency of voiceless consonants (for the group, O/E = 1.76; 95% CI [1.20, 2.491). Our results suggest that taken together, the names of chemotherapy medications contain an increased frequency of certain sounds associated with lightness, smallness and fastness. This finding raises important questions about the possible role of the names of medications in the experiences of cancer patients and providers. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Abel, Gregory A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. [Glinert, Lewis H.] Dartmouth Coll, Program Linguist & Cognit Sci, Hanover, NH 03755 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, 44 Binney St,Smith 271, Boston, MA 02115 USA. EM gregory_abel@dfci.harvard.edu; lewis.h.glinert@dartmouth.edu FU NCI NIH HHS [T32 CA009172] NR 34 TC 11 Z9 11 U1 1 U2 5 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 APR PY 2008 VL 66 IS 8 BP 1863 EP 1869 DI 10.1016/j.socscimed.2007.12.016 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 297EW UT WOS:000255600900020 PM 18243458 ER PT J AU Rosell, A Cuadrado, E Ortega-Aznar, A Hernandez-Guillamon, M Lo, EH Montaner, J AF Rosell, Anna Cuadrado, Eloy Ortega-Aznar, Arantxa Hernandez-Guillamon, Mar Lo, Eng H. Montaner, Joan TI MMP-9-Positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke SO STROKE LA English DT Article DE blood-brain barrier; collagen IV; hemorrhagic transformation; MMP-9; neutrophil; stroke ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; MATRIX-METALLOPROTEINASE EXPRESSION; MICROVASCULAR INTEGRITY; MATRIX-METALLOPROTEINASE-9; RATS; MICRODISSECTION; THROMBOLYSIS; INCREASES; ARTERY AB Background and Purpose - An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood-brain barrier breakdown after hemorrhagic transformation in human stroke. Methods - We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood-brain barrier vessels to study these MMPs. Results - Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (P < 0.0001 and P < 0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared to nonhemorrhagic and contralateral areas (P = 0.033 and P = 0.0001). No changes were found for MMP-2 content. Immunostaining revealed a strong MMP-9 -positive neutrophil infiltration surrounding brain microvessels associated with severe basal lamina type IV collagen degradation and blood extravasation. Microdissection confirmed that content of MMP-9 was similarly high in microvessel endothelium from hemorrhagic and infarcted areas compared to contralateral hemisphere vessels (P < 0.05), pointing to neutrophils surrounding dissected microvessels as the main source of MMP-9 in hemorrhagic areas. Conclusions - Our results show a strong neutrophil infiltration in the infarcted and hemorrhagic areas with local high MMP-9 content closely related to basal lamina collagen IV degradation and blood-brain barrier breakdown. Microvessel and inflammatory MMP-9 response are associated with hemorrhagic complications after stroke. C1 [Rosell, Anna; Cuadrado, Eloy; Hernandez-Guillamon, Mar; Montaner, Joan] Univ Autonoma Barcelona, Dept Neurol, Hosp Vall Hebron, Neurovasc Unit,Neurovasc Res Lab, Barcelona 08035, Spain. [Ortega-Aznar, Arantxa] Hosp Valle De Hebron, Dept Pathol, Barcelona, Spain. [Rosell, Anna; Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. RP Montaner, J (reprint author), Univ Autonoma Barcelona, Dept Neurol, Hosp Vall Hebron, Neurovasc Unit,Neurovasc Res Lab, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM 31862jmv@comb.es RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 NR 27 TC 182 Z9 201 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2008 VL 39 IS 4 BP 1121 EP 1126 DI 10.1161/STROKEAHA.107.500868 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 283JQ UT WOS:000254632900012 PM 18323498 ER PT J AU Holland, CM Smith, EE Csapo, I Gurol, ME Brylka, DA Killiany, RJ Blacker, D Albert, MS Guttmann, CRG Greenberg, SM AF Holland, Christopher M. Smith, Eric E. Csapo, Istvan Gurol, Mahmut Edip Brylka, Douglas A. Killiany, Ronald J. Blacker, Deborah Albert, Marilyn S. Guttmann, Charles R. G. Greenberg, Steven M. TI Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging SO STROKE LA English DT Article DE Alzheimer disease; cerebral amyloid angiopathy; magnetic resonance imaging; perfusion; white-matter hyperintensities ID MILD COGNITIVE IMPAIRMENT; VASCULAR RISK-FACTORS; CLINICAL-DIAGNOSIS; LESIONS; DEMENTIA; MRI; PROGRESSION; POPULATION; BRAIN; LEUKOARAIOSIS AB Background and Purpose - White-matter hyperintensities (WMHs) detected by magnetic resonance imaging are thought to represent the effects of cerebral small-vessel disease and neurodegenerative changes. We sought to determine whether the spatial distribution of WMHs discriminates between different disease groups and healthy aging individuals and whether these distributions are related to local cerebral perfusion patterns. Methods - We examined the pattern of WMHs by T2/fluid-attenuated inversion recovery-weighted magnetic resonance imaging in 3 groups of subjects: cerebral amyloid angiopathy (n = 32), Alzheimer disease or mild cognitive impairment (n = 41), and healthy aging (n = 29). WMH frequency maps were calculated for each group, and spatial distributions were compared by voxel-wise logistic regression. WMHs were also analyzed as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography atlas. Results - Although WMH volume was greater in cerebral amyloid angiopathy and Alzheimer disease/mild cognitive impairment than in healthy aging, there was no consistent difference in the spatial distributions when controlling for total WMH volume. Hyperintensities were most frequent in the deep periventricular WM in all 3 groups. A strong inverse correlation between hyperintensity frequency and normal perfusion was demonstrated in all groups, demonstrating that WMHs were most common in regions of relatively lower normal cerebral perfusion. Conclusions - WMHs show a common distribution pattern and predilection for cerebral WM regions with lower atlas-derived perfusion, regardless of the underlying diagnosis. These data suggest that across diverse disease processes, WM injury may occur in a pattern that reflects underlying tissue properties, such as relative perfusion. C1 [Holland, Christopher M.; Csapo, Istvan; Brylka, Douglas A.; Killiany, Ronald J.; Guttmann, Charles R. G.] Brigham & Womens Hosp, Ctr Neurol Imaging, Boston, MA 02115 USA. [Holland, Christopher M.; Killiany, Ronald J.] Harvard Univ, Sch Med, Dept Anat & Neurobiol, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. [Smith, Eric E.; Gurol, Mahmut Edip; Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trial Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Killiany, Ronald J.; Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. RP Guttmann, CRG (reprint author), Brigham & Womens Hosp, Ctr Neurol Imaging, 221 Longwood Ave, Boston, MA 02115 USA. EM guttmann@bwh.harvard.edu RI Smith, Eric/C-5443-2012; Gurol, Edip/J-2279-2014 OI Smith, Eric/0000-0003-3956-1668; Gurol, Edip/0000-0002-2169-4457 FU NCRR NIH HHS [P41 RR013218-010009, P41 RR13218-01, P41 RR013218]; NIA NIH HHS [P01 AG004953, P01 AG004953-190006, P01 AG004953-200006, P01 AG004953-210006, P01 AG004953-220006, P01 AG004953-230006, P01 AG04953, R01 AG026484, R01 AG026484-01, R01 AG026484-02, R01 AG026484-03, R01 AG026484-04, R01 AG026484-05]; NINDS NIH HHS [F30 NS049808, F30 NS049808-01A2, F30 NS049808-02, F30 NS049808-03, K24 NS056207, K24 NS056207-01, K24 NS056207-02, K24 NS056207-03, K24 NS056207-04] NR 46 TC 92 Z9 94 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2008 VL 39 IS 4 BP 1127 EP 1133 DI 10.1161/STROKEAHA.107.497438 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 283JQ UT WOS:000254632900013 PM 18292383 ER PT J AU Ay, H Arsava, EM Vangel, M Oner, B Zhu, M Wu, O Singhal, A Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Vangel, Mark Oner, Banu Zhu, Mingwang Wu, Ona Singhal, Aneesh Koroshetz, Walter J. Sorensen, A. Gregory TI Interexaminer difference in infarct volume measurements on MRI - A source of variance in stroke research SO STROKE LA English DT Article DE acute stroke; diffusion-weighted imaging; MRI; neuroradiology ID CEREBRAL-BLOOD-FLOW; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; HYPERACUTE STROKE; INTEROBSERVER AGREEMENT; INTERRATER RELIABILITY; DIFFUSION; PERFUSION; CLASSIFICATION; MISMATCH AB Background and Purpose - The measurement of ischemic lesion volume on diffusion- (DWI) and perfusion-weighted MRI (PWI) is examiner dependent. We sought to quantify the variance imposed by measurement error in DWI and PWI lesion volume measurements in ischemic stroke. Methods - Fifty-eight consecutive patients with DWI and PWI within 12 hours of symptom onset and follow-up MRI on >= day-5 were studied. Two radiologists blinded to each other measured lesion volumes by manual outlining on each image. Interexaminer reliability was evaluated by intraclass correlation coefficients (ICC) and relative paired difference or RPD (ratio of difference between 2 measurements to their mean). The ratio of between-examiner variability to between-subject variability (variance ratio) was calculated for each imaging parameter. Results - The correlation (ICC) between examiners ranged from 0.93 to 0.99. The median RPD was 10.0% for DWI, 14.1% for mean transit time, 18.9% for cerebral blood flow, 21.0% for cerebral blood volume, 16.8% for DWI/MTT mismatch, and 6.3% for chronic T2-weighted images. There was negative correlation between RPD and lesion volume in all but chronic T2-weighted images. The variance ratio ranged between 0.02 and 0.10. Conclusion - Despite high correlation between volume measurements of abnormal regions on DWI and PWI by different examiners, substantial differences in individual measurements can still occur. The magnitude of variance from measurement error is primarily determined by the type of imaging and lesion volume. Minimizing this source of variance will better enable imaging to deliver on its promise of smaller sample size. C1 [Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA. [Ay, Hakan; Arsava, E. Murat; Vangel, Mark; Oner, Banu; Zhu, Mingwang; Wu, Ona; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [NS38477, R01-NS38477-04] NR 28 TC 36 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2008 VL 39 IS 4 BP 1171 EP 1176 DI 10.1161/STROKEAHA.107.502104 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 283JQ UT WOS:000254632900020 PM 18292377 ER PT J AU Grotta, JC Jacobs, TP Koroshetz, WJ Moskowitz, MA AF Grotta, James C. Jacobs, Thomas P. Koroshetz, Walter J. Moskowitz, Michael A. TI Stroke program review group - An interim report SO STROKE LA English DT Article DE stroke; research; ischemia; hemorrhage AB The Stroke Program Review Group (SPRG) met for the first time in 2001 to identify and prioritize scientific needs and opportunities in stroke, and to consider strategies to address them. Out of this meeting came a set of scientific and resource recommendations (http://www.ninds.nih.gov/find_people/groups/stroke_prg/index.htm) including the recommendation to review progress after 5 years. In September 2006, the NINDS convened a second SPRG of prominent scientists, clinicians, industry leaders, and patient advocates to discuss progress since the first SPRG and to examine new opportunities in light of more recent advances. The report of the second SPRG meeting is found at http://www.ninds.nih.gov/find_people/groups/stroke_prg/09_2006_stroke_prg_report.htm. In this brief interim report, we list and summarize progress in each of the investigational domains outlined in the SPRG with an emphasis on those advances directly resulting from NINDS-funded research. Also listed are the top 2 or 3 research priorities for the next 5-year cycle for each investigational theme. What emerges from the first 2 reports is a clear set of priorities that have since been complemented by exciting advances that are likely to be the focus of a follow-up report from the next SPRG in 2010. C1 [Grotta, James C.] Univ Texas Houston, Sch Med, Dept Neurol, Houston, TX 77080 USA. [Jacobs, Thomas P.] NINDS, Ctr Neurosci, Extramural Res Program, NIH, Bethesda, MD 20892 USA. [Koroshetz, Walter J.] NINDS, Ctr Neurosci, NINDS Off Director, NIH, Bethesda, MD 20892 USA. [Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Grotta, JC (reprint author), Univ Texas Houston, Sch Med, Dept Neurol, 6431 Fannin St, Houston, TX 77080 USA. EM james.c.grotta@uth.tmc.edu NR 0 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2008 VL 39 IS 4 BP 1364 EP 1370 DI 10.1161/STROKEAHA.107.510776 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 283JQ UT WOS:000254632900053 PM 18309142 ER PT J AU Willingham, FF Gee, DW Lauwers, GY Brugge, WR Rattner, DW AF Willingham, F. F. Gee, D. W. Lauwers, G. Y. Brugge, W. R. Rattner, D. W. TI Natural orifice transesophageal mediastinoscopy and thoracoscopy SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE lymph node biopsy; mediastinoscopy; notes; pleural biopsy; thoracoscopy; transesophageal ID PORCINE MODEL; ABDOMINAL EXPLORATION; ORGAN RESECTION; NOTES SURVIVAL; CHOLECYSTECTOMY; PERITONEOSCOPY; FEASIBILITY; ANASTOMOSIS; EXPERIENCE; ENDOSCOPY AB Background Thoracoscopy and mediastinoscopy are common procedures with painful incisions and prominent scars. A natural orifice transesophageal endoscopic surgical (NOTES) approach could reduce pain, eliminate intercostal neuralgia, provide access to the posterior mediastinal compartment, and improve cosmesis. In addition NOTES esophageal access routes also have the potential to replace conventional thoracoscopic approaches for medial or hilar lesions. Methods Five healthy Yorkshire swine underwent nonsurvival natural orifice transesophageal mediastinoscopy and thoracoscopy under general anesthesia. An 8- to 9.8-mm video endoscope was introduced into the esophagus, and a 10-cm submucosal tunnel was created with blunt dissection. The endoscope then was passed through the muscular layers of the esophagus into the mediastinal space. The mediastinal compartment, pleura, lung, mediastinal lymph nodes, thoracic duct, vagus nerves, and exterior surface of the esophagus were identified. Mediastinal lymph node resection was easily accomplished. For thoracoscopy, a small incision was created through the pleura, and the endoscope was introduced into the thoracic cavity. The lung, chest wall, pleura, pericardium, and diaphragmatic surface were identified. Pleural biopsies were obtained with endoscopic forceps. The endoscope was withdrawn and the procedure terminated. Results Mediastinal and thoracic structures could be identified without difficulty via a transesophageal approach. Lymph node resection was easily accomplished. Pleural biopsy under direct visualization was feasible. Selective mainstem bronchus intubation and collapse of the ipsilateral lung facilitated thoracoscopy. In one animal, an inadvertent 4-mm lung incision resulted in a pneumothorax. This was decompressed with a small venting intercostal incision, and the remainder of the procedure was completed without difficulty. Conclusions Transesophageal endoscopic mediastinoscopy, lymph node resection, thoracoscopy, and pleural biopsy are feasible and provide excellent visualization of mediastinal and intrathoracic structures. Survival studies will be needed to confirm the safety of this approach. C1 [Gee, D. W.; Rattner, D. W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Willingham, F. F.; Brugge, W. R.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. [Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Gee, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM dgee@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 24 TC 49 Z9 52 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD APR PY 2008 VL 22 IS 4 BP 1042 EP 1047 DI 10.1007/s00464-007-9668-z PG 6 WC Surgery SC Surgery GA 287TR UT WOS:000254939900033 PM 18030521 ER PT J AU Albo, D Farrow, B Berger, DH AF Albo, Daniel Farrow, Buckminster Berger, David H. TI Translation of recent advances and discoveries in molecular biology and immunology in the diagnosis and treatment of pancreatic cancer SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PHASE-I TRIAL; ADVANCED SOLID TUMORS; MATRIX-METALLOPROTEINASE INHIBITOR; PROTEIN TRANSFERASE INHIBITOR; SMALL-CELL LUNG; MONOCLONAL-ANTIBODY; FACTOR RECEPTOR; RANDOMIZED-TRIAL; PEPTIDE VACCINATION AB Recent advances in understanding the molecular mechanisms of cancer progression have allowed for targeted approaches to the diagnosis and treatment of pancreatic cancer. New biologic markers are emerging that may improve the ability to detect these tumors earlier. Targeted biologic cancer therapies promise more effective and less toxic systemic treatment options. Although a clear "magic bullet" has yet to emerge, this type of targeted approach offers hope in the management of this dreadful disease. This article offers an update on these promising diagnostic and treatment modalities. C1 [Albo, Daniel; Farrow, Buckminster; Berger, David H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Albo, D (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112A, Houston, TX 77030 USA. EM dalbo@bcm.tmc.edu NR 82 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2008 VL 17 IS 2 BP 357 EP + DI 10.1016/j.soc.2007.12.004 PG 21 WC Oncology; Surgery SC Oncology; Surgery GA 294QL UT WOS:000255420500008 PM 18375357 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Complex EPSCs evoked in substantia nigra reticulata neurons are disrupted by repetitive stimulation of the subthalamic nucleus SO SYNAPSE LA English DT Article DE subthalamic nucleus; substantia nigra reticulata; patch clamp; synaptic transmission; brain slice; complex EPSC; high-frequency stimulation; low-frequency stimulation ID HIGH-FREQUENCY STIMULATION; DEEP BRAIN-STIMULATION; PARS-RETICULATA; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; BASAL GANGLIA; RAT; RECEPTORS; TRANSMISSION; ACTIVATION AB Although substantia nigra reticulata (SNR) neurons fire bursts of action potentials during normal movement, excessive burst firing correlates with symptoms of Parkinson's disease. A major excitatory output from the subthalamic nucleus (STN) to the SNR is thought to provide the synaptic impetus for burst firing in SNR neurons. Using patch pipettes to record from SNR neurons in rat brain slices, we found that a single electrical stimulus delivered to the STN evokes a burst of action potentials. Under voltage-clamp conditions, STN stimulation evokes a complex EPSC that is comprised of an initial monosynaptic EPSC followed by a series of late EPSCs superimposed on a long-lasting inward current. Using varied stimulation frequencies, we found that the initial EPSC was significantly reduced or abolished after 2 s of 50-100 Hz STN stimulation. However, only 4 s of 1 Hz stimulation was required to abolish the late component of the complex EPSC. We suggest that differential effects of repetitive STN stimulation on early and late components of complex EPSCS may help explain the frequency-dependent effects of deep brain stimulation of the STN that is used in the treatment of Parkinson's disease. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Vet Affairs Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NINDS NIH HHS [R01 NS038715-09, R01 NS060662, R01 NS038715, R01 NS038175, NS 38175, R01 NS060662-01A1] NR 26 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2008 VL 62 IS 4 BP 237 EP 242 DI 10.1002/syn.20488 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 274ZB UT WOS:000254040200001 PM 18236470 ER PT J AU Mahoney, DMF Mutschler, PH Tarlow, B Liss, E AF Mahoney, Diane M. F. Mutschler, Phyllis H. Tarlow, Barbara Liss, Ellen TI Real world implementation lessons and outcomes from the Worker Interactive Networking (WIN) project: workplace-based online caregiver support and remote monitoring of elders at home SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article DE Worker Interactive Networking; caregiver support; home monitoring; elders ID EMPLOYMENT; STRAIN AB The objective of this research was to determine the feasibility of and receptivity to the first computerized workplace-based direct caregiver intervention and to assess the effects on businesses, working family caregivers, and their elderly relatives. Working family caregivers, with at least one health and/ or safety concern related to an elder residing alone at home during the workday, were recruited from five companies (n = 27). Caregivers received free computer access to the Worker Interactive Networking ( WIN) Internet online caregiver support group and a remote elder monitoring system at home for 6 months. The remote monitoring system provided Web- based status reports and e- mail/ pager alerts when individualized parameters were exceeded. Motion sensor signals were transmitted to a transponder that uploaded via wireless cellular communications to the project server, thereby not interfering with elders' telephone use. Formative qualitative analyses clarified acceptance and implementation issues. Summative quantitative evaluation determined pilot intervention effects and was conducted by external evaluators. Despite interoperability deployed across four states to a variety of businesses and housing types. Positive results occurred on worker morale, productivity, and reduction of caregiver stress. Participants found it easy to learn and use. Elders did not find the technology " intrusive" or " isolating." Contrary to their expectations, managers reported no abuse of Internet access. Workers expressed a willingness to pay for a similar system in the future ranging from $ 10 to $ 130, depending on the features. They would pay the most for the option involving a geriatric nurse coach. The WIN system innovatively tailored to users' wants, and provided users customized control and personalized support. Use of the system was associated with positive outcomes. Enrollment response suggests a specific niche market for remote home monitoring, making it a manageable employee benefit. C1 [Mahoney, Diane M. F.; Tarlow, Barbara] Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Boston, MA 02129 USA. [Mutschler, Phyllis H.; Liss, Ellen] Brandeis Univ, Natl Ctr Women & Aging, Waltham, MA USA. RP Mahoney, DMF (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Rm 419,36 1st Ave, Boston, MA 02129 USA. EM dmahoney@mghihp.edu OI Mahoney, Diane/0000-0002-6415-475X NR 17 TC 16 Z9 16 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD APR PY 2008 VL 14 IS 3 BP 224 EP 234 DI 10.1089/tmj.2007.0046 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 300KY UT WOS:000255823900033 PM 18570545 ER PT J AU Krupinski, E Burdick, A Pak, H Bocachica, J Earles, L Edison, K Goldyne, M Hirota, T Kvedar, J Mckoy, K Oh, D Siegel, D Antoniotti, N Camacho, I Carnahan, L Boynton, P Bakalar, R Evans, R Kinel, A Kuzmak, P Madden, BC Peters, S Rosenthal, L Simmons, S Bernard, J Linkous, J AF Krupinski, Elizabeth Burdick, Anne Pak, Hon Bocachica, John Earles, Lucius Edison, Karen Goldyne, Marc Hirota, Tom Kvedar, Joseph Mckoy, Karen Oh, Dennis Siegel, Dan Antoniotti, Nina Camacho, Ivan Carnahan, Lisa Boynton, Paul Bakalar, Richard Evans, Richard Kinel, Al Kuzmak, Peter Madden, Brian C. Peters, Sandra Rosenthal, Lynne Simmons, Scott Bernard, Jordana Linkous, Jonathan TI American telemedicine association's practice guidelines for teledermatology SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COST-MINIMIZATION ANALYSIS; REALTIME TELEDERMATOLOGY; FORWARD TELEDERMATOLOGY; MULTICENTER TELEDERMATOLOGY; DERMATOLOGY REFERRALS; PATIENT SATISFACTION; DIAGNOSTIC-ACCURACY; CONVENTIONAL CARE; NORTHERN-IRELAND AB The American Telemedicine Association ( ATA), with more than 2,500 members, is the principal organization of telemedicine practitioners in the United States. The ATA is a nonprofit society that seeks to bring together diverse groups from traditional medicine, nursing, allied health professionals, academic medical centers, technology and telecommunications companies, e- health, medical societies, government and others to overcome barriers to the advancement of telemedicine through the professional, ethical, and equitable improvement in healthcare delivery. The ATA has strong ties and strategic relationships with host organizations with other international telemedicine societies. The ATA will occasionally define new practice guidelines and technical standards for telehealth practice to help advance the science of telehealth and to improve the quality of service to patients. Existing practice guidelines and technical standards will be reviewed for revision or renewal periodically. The practice guidelines and technical standards generated by ATA have undergone a thorough consensus and rigorous review, with final approval by the ATA Board of Directors. The practice guidelines and technical standards recognize that safe and effective telehealth practices require specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standard by entities that do not provide these services is not authorized. C1 [Krupinski, Elizabeth] Univ Arizona, Dept Radiol Res, Arizona Telemed Program, Tucson, AZ 85724 USA. [Burdick, Anne; Simmons, Scott] Univ Miami, Miller Sch Med, Miami, FL 33152 USA. [Pak, Hon] Telemed & Adv Technol Res Ctr, Adv Informat Technol Grp, Ft Detrick, MD USA. [Bocachica, John] Dept Dermatol & Teledermatol Alaska Fed Hlth Care, Anchorage, AK USA. [Earles, Lucius] Mt Sinai Hosp, Dermatol Sect, Dept Med, Chicago, IL USA. [Edison, Karen] Univ Missouri Hlth Care, Dept Dermatol, Columbia, MO USA. [Goldyne, Marc; Oh, Dennis] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Hirota, Tom] Uniformed Serv Univ Hlth Sci, Dermatol Serv, Madigan Army Med Ctr, Bethesda, MD 20814 USA. [Hirota, Tom] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Dermatol, Bethesda, MD 20814 USA. [Kvedar, Joseph] Harvard Univ, Sch Med, Dept Dermatol, Ctr Connected Hlth Partners HealthCare Syst Inc, Boston, MA 02115 USA. [Mckoy, Karen] Lahey Clin Fdn, Dept Dermatol, Burlington, MA USA. [Mckoy, Karen] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Oh, Dennis] Dermatol Serv, San Francisco VA Med Ctr, San Francisco, CA USA. [Siegel, Dan] Suny Downstate Med Ctr, Dept Dermatol, Brooklyn, NY 11203 USA. [Antoniotti, Nina] Marshfield Clin TeleHlth Network, Marshfield, WI USA. [Camacho, Ivan] Univ Miami, Dept Dermatol & Cutaneous Surg, Miami, FL 33152 USA. [Carnahan, Lisa; Boynton, Paul; Rosenthal, Lynne] Informat Technol Lab Natl Inst Stand & Technol, Gaithersburg, MD USA. [Bakalar, Richard] IBM Corp, IBM Global Healthcare, Armonk, NY 10504 USA. [Kinel, Al] Alliances Kodak Corp, Rochester, NY USA. [Kuzmak, Peter] Dept Vet Affairs VistA Imaging Project, Silver Spring, MD USA. [Madden, Brian C.] Univ Rochester, VISN Telemed Dept Vet Affairs 2, Rochester, NY USA. [Madden, Brian C.] Univ Rochester, Dept Dermatol, Rochester, NY 14627 USA. [Peters, Sandra] Amer Acad Dermatol, Washington, DC USA. [Bernard, Jordana; Linkous, Jonathan] Amer Telemed Assoc, Washington, DC USA. [Evans, Richard] Utah TeleHlth Network, Salt Lake City, UT USA. RP Krupinski, E (reprint author), Univ Arizona, Dept Radiol Res, Arizona Telemed Program, 1609 N Warren Bldg 211,Room 112, Tucson, AZ 85724 USA. EM krupinski@radiology.arizona.edu NR 58 TC 33 Z9 33 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD APR PY 2008 VL 14 IS 3 BP 289 EP 302 DI 10.1089/tmj.2007.0129 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 300KY UT WOS:000255823900043 PM 18570555 ER PT J AU Dransfield, MT Rowe, SM Johnson, JE Bailey, WC Gerald, LB AF Dransfield, M. T. Rowe, S. M. Johnson, J. E. Bailey, W. C. Gerald, L. B. TI Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD SO THORAX LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; MYOCARDIAL-INFARCTION; HEART-FAILURE; MORTALITY; MORBIDITY; CORONARY; INTERVENTION; EPIDEMIOLOGY; MANAGEMENT; REDUCTION AB Background: Cardiovascular disease is a major cause of death in patients with chronic obstructive pulmonary disease (COPD) and predicts hospitalisation for acute exacerbation, in-hospital death and post-discharge mortality. Although beta blockers improve cardiovascular outcomes, patients with COPD often do not receive them owing to concerns about possible adverse pulmonary effects. There are no published data about b blocker use among inpatients with COPD exacerbations. A study was undertaken to identify factors associated with b blocker use in this setting and to determine whether their use is associated with decreased in-hospital mortality. Methods: Administrative data from the University of Alabama Hospital were reviewed and patients admitted between October 1999 and September 2006 with an acute exacerbation of COPD as a primary diagnosis or as a secondary diagnosis with a primary diagnosis of acute respiratory failure were identified. Demographic data, comorbidities and medication use were recorded and subjects receiving beta blockers were compared with those who did not. Multivariate regression analysis was performed to determine predictors of in-hospital death after controlling for known covariates and the propensity to receive beta blockers. Results: 825 patients met the inclusion criteria. Inhospital mortality was 5.2%. Those receiving beta blockers (n = 142) were older and more frequently had cardiovascular disease than those who did not. In multivariate analysis adjusting for potential confounders including the propensity score, beta blocker use was associated with reduced mortality (OR = 0.39; 95% CI 0.14 to 0.99). Age, length of stay, number of prior exacerbations, the presence of respiratory failure, congestive heart failure, cerebrovascular disease or liver disease also predicted in-hospital mortality (p<0.05). Conclusions: The use of beta blockers by inpatients with exacerbations of COPD is well tolerated and may be associated with reduced mortality. The potential protective effect of beta blockers in this population warrants further study. C1 [Dransfield, M. T.; Rowe, S. M.; Johnson, J. E.; Bailey, W. C.; Gerald, L. B.] Univ Alabama, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Dransfield, M. T.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Dransfield, MT (reprint author), 215 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. EM mdransfield99@msn.com FU NIDDK NIH HHS [K23 DK075788-01] NR 38 TC 90 Z9 96 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD APR PY 2008 VL 63 IS 4 BP 301 EP 305 DI 10.1136/thx.2007.081893 PG 5 WC Respiratory System SC Respiratory System GA 278MF UT WOS:000254289500004 PM 17951276 ER PT J AU Stowell, C AF Stowell, Christopher TI Blood substitutes: time for a deep breath SO TRANSFUSION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02115 USA. RP Stowell, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02115 USA. EM cstowell@partners.org NR 4 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2008 VL 48 IS 4 BP 574 EP 575 DI 10.1111/j.1537-2995.2008.01675.x PG 2 WC Hematology SC Hematology GA 278IC UT WOS:000254277500001 PM 18366459 ER PT J AU Burket, CT Montgomery, JE Thummel, R Kassen, SC LaFave, MC Langenau, DM Zon, LI Hyde, DR AF Burket, Christopher T. Montgomery, Jacob E. Thummel, Ryan Kassen, Sean C. LaFave, Matthew C. Langenau, David M. Zon, Leonard I. Hyde, David R. TI Generation and characterization of transgenic zebrafish lines using different ubiquitous promoters SO TRANSGENIC RESEARCH LA English DT Article DE zebrafish; central nervous system; ubiquitous; promoter; Tol2; adult expression pattern ID GREEN FLUORESCENT PROTEIN; MUTATIONS AFFECTING DEVELOPMENT; DANIO-RERIO; FIN REGENERATION; GENE-EXPRESSION; MEDAKA FISH; IN-VIVO; ALBINO ZEBRAFISH; ORYZIAS-LATIPES; CELL LINEAGES AB Two commonly used promoters to ubiquitously express transgenes in zebrafish are the Xenopus laevis elongation factor 1 alpha promoter (XIEef1a1) and the zebrafish histone variant H2A.F/ Z (h2afv) promoter. Recently, transgenes utilizing these promoters were shown to be silenced in certain adult tissues, particularly the central nervous system. To overcome this limitation, we cloned the promoters of four zebrafish genes that likely are transcribed ubiquitously throughout development and into the adult. These four genes are the TATA box binding protein gene, the taube nuss-like gene, the eukaryotic elongation factor 1-gamma gene, and the beta-actin-1 gene. We PCR amplified approximately 2.5 kb upstream of the putative translational start site of each gene and cloned each into a To12 expression vector that contains the EGFP reporter transgene. We used these four To12 vectors to independently generate stable transgenic fish lines for analysis of transgene expression during development and in the adult. We demonstrated that all four promoters drive a very broad pattern of EGFP expression throughout development and the adult. Using the retina as a well-characterized component of the CNS, all four promoters appeared to drive EGFP expression in all neuronal and non-neuronal cells of the adult retina. In contrast, the h2afv promoter failed to express EGFP in the adult retina. When we examined EGFP expression in the various cells of the blood cell lineage, we observed that all four promoters exhibited a more heterogenous expression pattern than either the XlEef1a1 or h2aft promoters. While these four ubiquitous promoters did not express EGFP in all the adult blood cells, they did express EGFP throughout the CNS and in broader expression patterns in the adult than either the XlEef1a1 or h2afv promoters. For these reasons, these four promoters will be valuable tools for expressing transgenes in adult zebrafish. C1 [Burket, Christopher T.; Montgomery, Jacob E.; Thummel, Ryan; Kassen, Sean C.; LaFave, Matthew C.; Hyde, David R.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Langenau, David M.; Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp Boston, HHMI, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Stem Cell Program,Howard Hughes Med Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst,Childrens Hosp, Howard Hughes Med Inst,Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Howard Hughes Med Inst,Dana Farber Canc Inst, Boston, MA 02115 USA. [Burket, Christopher T.; Montgomery, Jacob E.; Thummel, Ryan; Kassen, Sean C.; LaFave, Matthew C.; Hyde, David R.] Univ Notre Dame, Ctr Zebrafish Res, Notre Dame, IN 46556 USA. RP Hyde, DR (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. EM dhyde@nd.edu OI LaFave, Matthew/0000-0001-9165-041X FU NEI NIH HHS [R21 EY017134-02, R21 EY017134, R21 EY017134-01, R21-EY017134] NR 62 TC 21 Z9 21 U1 1 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD APR PY 2008 VL 17 IS 2 BP 265 EP 279 DI 10.1007/s11248-007-9152-5 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 279KK UT WOS:000254353900010 PM 17968670 ER PT J AU Kahle, KT Rinehart, J Giebisch, G Gamba, G Hebert, SC Lifton, RP AF Kahle, Kristopher T. Rinehart, Jesse Giebisch, Gerhard Gamba, Gerardo Hebert, Steven C. Lifton, Richard P. TI A novel protein kinase signaling pathway essential for blood pressure regulation in humans SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Article; Proceedings Paper CT Meeting on Low Renin Hypertension CY JUN, 2007 CL Frascati, ITALY ID PSEUDOHYPOALDOSTERONISM TYPE-II; PARACELLULAR CL-PERMEABILITY; WNK KINASES; MOLECULAR PATHOGENESIS; ESSENTIAL-HYPERTENSION; SURFACE EXPRESSION; COLLECTING DUCT; ION-TRANSPORT; NA+ CHANNEL; MUTANT WNK4 AB The discovery that mutations in WNK4 [encoding a member of the WNIK family - so named because of the unique substitution of cysteine for lysine at a nearly invariant residue within subdomain II of its catalytic core: with no K (lysine)] cause pseudohypoaldosteronism type II, an autosomal dominant form of human hypertension, provided the initial clue that this serine/threonine kinase is a crucial part of a complex renal salt regulatory system. Recent findings from physiological studies of WNK4 in Xenopus laevis oocytes, mammalian cell systems and in vivo in mouse models have provided novel insights into the mechanisms by which the kidney regulates salt homeostasis, and therefore blood pressure, downstream of aldosterone signaling in mammals. The current evidence supports a model in which WNK4 coordinates the activities of diverse aldosterone-sensitive mediators of ion transport in the distal nephron to promote normal homeostasis in response to physiological perturbation. C1 [Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Rinehart, Jesse; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Rinehart, Jesse; Lifton, Richard P.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Rinehart, Jesse; Lifton, Richard P.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. [Rinehart, Jesse; Lifton, Richard P.] Howard Hughes Med Inst, New Haven, CT 06510 USA. [Giebisch, Gerhard; Hebert, Steven C.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Gamba, Gerardo] Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. [Gamba, Gerardo] Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 14000, DF, Mexico. RP Kahle, KT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM kkahle@partners.org FU NIDDK NIH HHS [DK-64635] NR 32 TC 21 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2008 VL 19 IS 3 BP 91 EP 95 DI 10.1016/j.tem.2008.01.001 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 295CP UT WOS:000255452900004 PM 18280177 ER PT J AU Franklin, A Blanden, RV AF Franklin, Andrew Blanden, Robert V. TI The strand bias paradox of somatic hypermutation at immunoglobulin loci SO TRENDS IN IMMUNOLOGY LA English DT Review ID CLASS-SWITCH RECOMBINATION; DNA-POLYMERASE-ETA; CYTIDINE DEAMINASE AID; CELL-CYCLE REGULATION; GERMINAL-CENTERS; ANTIBODY DIVERSIFICATION; GENE HYPERMUTATION; MISMATCH REPAIR; B-CELLS; MUTATION AB Somatic hypermutation has two phases: phase 1 affects cytosine-guanine (C/G) pairs and is triggered by the deamination of cytosine residues in DNA to uracill; phase 2 affects mostly adenine-thymine (A/T) pairs and is induced by the detection of uracil lesions in DNA. It is not known how, at V(D)J genes in mice, hypermutations accumulate at A/T pairs with strand bias without perturbing the strand unbiased accumulation of hypermutations at C/G pairs. Additionally, it is not known why, in contrast, at switch regions in mice, both C/G-targeted and A/T-targeted hypermutations accumulate in a strand unbiased manner. To explain the strand bias paradox, we propose that phase 1 and phase 2 hypermutations are generated at different stages of the cell cycle. C1 [Franklin, Andrew] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Franklin, Andrew] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Blanden, Robert V.] Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia. RP Franklin, A (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. EM franklin@idi.harvard.edu NR 46 TC 7 Z9 8 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD APR PY 2008 VL 29 IS 4 BP 167 EP 172 DI 10.1016/j.it.2008.01.008 PG 6 WC Immunology SC Immunology GA 295IX UT WOS:000255469300021 PM 18329339 ER PT J AU Westermarck, J Hahn, WC AF Westermarck, Jukka Hahn, William C. TI Multiple pathways regulated by the tumor suppressor PP2A in transformation SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID PROTEIN PHOSPHATASE 2A; SMALL-T-ANTIGEN; HUMAN CELL-TRANSFORMATION; ANCHORAGE-INDEPENDENT GROWTH; MAP KINASE PATHWAY; C-MYC; RAL-GTPASES; SUBUNIT INTERACTION; BREAST-CANCER; PPP2R1B GENE AB Reversible protein phosphorylation plays a central role in regulating intracellular signaling. Dysregulation of the mechanisms that regulate phosphorylation plays a direct role in cancer initiation and maintenance. Although abundant evidence supports the role of kinase oncogenes in cancer development, recent work has illuminated the role of specific protein phosphatases in malignant transformation. Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase in mammalian cells. Inactivation of PP2A by viral oncoproteins, mutation of specific subunits or overexpression of endogenous inhibitors contributes to cell transformation by regulating specific phosphorylation events. Here, we review recent progress in our understanding of how PP2A regulates mitogenic signaling pathways in cancer pathogenesis and how PP2A activity is modulated in human cancers. C1 [Westermarck, Jukka] Univ Tampere, Inst Med Technol, Tampere 33520, Finland. [Westermarck, Jukka] Tampere Univ Hosp, Tampere 33520, Finland. [Westermarck, Jukka] Univ Turku, Ctr Biotechnol, FIN-20520 Turku, Finland. [Westermarck, Jukka] Abo Akad Univ, FIN-20520 Turku, Finland. [Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02139 USA. [Hahn, William C.] MIT, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Univ Tampere, Inst Med Technol, Tampere 33520, Finland. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [P01 CA50661] NR 114 TC 174 Z9 179 U1 1 U2 13 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 APR PY 2008 VL 14 IS 4 BP 152 EP 160 DI 10.1016/j.molmed.2008.02.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 297JH UT WOS:000255612500002 PM 18329957 ER PT J AU de Koning, EJP Bonner-Weir, S Rabelink, TJ AF de Koning, Eelco J. P. Bonner-Weir, Susan Rabelink, Ton J. TI Preservation of beta-cell function by targeting beta-cell mass SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID GLUCAGON-LIKE PEPTIDE-1; TYPE-2 DIABETES-MELLITUS; EPIDERMAL-GROWTH-FACTOR; NF-KAPPA-B; STIMULATED INSULIN-SECRETION; RENIN-ANGIOTENSIN SYSTEM; PANCREATIC-ISLETS; DIPEPTIDYL PEPTIDASE-4; GLUCOSE-TOLERANCE; OXIDATIVE STRESS AB Type 2 diabetes is characterized by progressive beta-cell dysfunction and a reduction in beta-cell mass. Pancreatic islets are a target for adverse effectors such as high concentrations of glucose, pro-inflammatory cytokines and increased free fatty acid concentrations - which are associated with adiposity, insulin resistance and the induction of beta-cell apoptosis. If the beta-cell mass is already below the threshold for maintaining normoglycemia, the expansion of beta-cell mass is the only option for achieving normoglycemia without the use of additional glucose-lowering agents. Therapies based on glucagon-like peptide-1 and combinations of growth factors such as epidermal growth factor and gastrin are promising new strategies for beta-cell preservation. In this review, we address the mechanisms involved in beta-cell dysfunction and beta-cell loss, and provide a rationale for pharmacological intervention for the preservation and/or expansion of R-cell mass in type 2 diabetes. C1 [de Koning, Eelco J. P.; Rabelink, Ton J.] Leiden Univ, Med Ctr, Dept Nephrol, NL-2300 RC Leiden, Netherlands. [de Koning, Eelco J. P.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, NL-2300 RC Leiden, Netherlands. [Bonner-Weir, Susan] Harvard Univ, Dept Islet Transplantat & Cell Biol, Joslin Diabet Ctr, Boston, MA 02215 USA. RP de Koning, EJP (reprint author), Leiden Univ, Med Ctr, Dept Nephrol, POB 9600, NL-2300 RC Leiden, Netherlands. EM e.dekoning@lumc.nl RI Rabelink, Ton/A-5316-2008 OI Rabelink, Ton/0000-0001-6780-5186 NR 117 TC 34 Z9 35 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 2008 VL 29 IS 4 BP 218 EP 227 DI 10.1016/j.tips.2008.02.001 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 294QE UT WOS:000255419800009 PM 18359095 ER PT J AU Cozen, W Ferreira, MAR AF Cozen, Wendy Ferreira, Manuel A. R. TI Understanding the asthma epidemic: Can twin studies help? SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Editorial Material C1 [Cozen, Wendy] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Cozen, Wendy] Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA USA. [Ferreira, Manuel A. R.] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA USA. [Ferreira, Manuel A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP Cozen, W (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1441 Eastlake Ave,MC 9175, Los Angeles, CA 90089 USA. EM wcozen@usc.edu RI Ferreira, Manuel/D-3609-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD APR PY 2008 VL 11 IS 2 BP 111 EP 111 DI 10.1375/twin.11.2.111 PG 1 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 284GD UT WOS:000254694000001 PM 18361710 ER PT J AU Kerfoot, BP Turek, PJ AF Kerfoot, B. Price Turek, Paul J. TI What every graduating medical student should know about urology: The stakeholder viewpoint SO UROLOGY LA English DT Article ID UNITED-STATES; CONTROLLED-TRIAL; EDUCATION; CURRICULUM; DECLINE; SCHOOLS AB OBJECTIVES What should every medical student know about urology upon graduating from medical school? To answer this question, we conducted a survey of key stakeholders in an effective medical Student education in urology. METHODS Directors of the generalist residencies in the United States (emergency medicine, family medicine, internal medicine, and pediatrics), directors Of urology residencies, medical student educators in urology, and applicants to the 2006 urology residency match were invited to complete an online survey. Participants were asked to select the 5 most important topics to be included in a core urology curriculum for all medical Students. RESULTS Among 1859 stakeholders surveyed, response rates by stakeholder cohort ranged from 67% to 26% (overall 44%). There was marked homogeneity among participant groups as to what respondents considered to be the most important topics for a core urology curriculum for medical Students. Based on aggregate data, the 8 most commonly cited topics included urinary stone disease (75% of respondents), hematuria (65%), urinary tract infections in adults (53%), benign prostatic hyperplasia (52%), urinary incontinence (45%), prostate cancer (45%), screening with prostate-specific antigen (33%), and testis torsion (24%). CONCLUSIONS This Survey has identified the most important urology topics about which medical students should learn before graduation. Work is currently under way under the aegis of the American Urological Association to develop materials to standardize student education in these core topics across the United States. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151D1A, Boston, MA 02130 USA. EM price.kerfoot@gmait.com NR 17 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2008 VL 71 IS 4 BP 549 EP 553 DI 10.1016/j.urology.2007.12.010 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 285ZD UT WOS:000254813800001 PM 18387383 ER PT J AU Gulmaraes, AR Tabatabei, S Dahl, D McDougal, WS Weissleder, R Harisinghani, MG AF Gulmaraes, Alexander R. Tabatabei, Shahin Dahl, Douglas McDougal, W. Scott Weissleder, Ralph Harisinghani, Mukesh G. TI Pilot study evaluating use of lymphotrophic nanoparticle-enhanced magnetic resonance imaging for assessing lymph nodes in renal cell cancer SO UROLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; RADICAL NEPHRECTOMY; CARCINOMA; MR; METASTASES; LYMPHADENECTOMY; DISSECTION; SURVIVAL; BENEFITS; SURGERY AB OBJECTIVE To assess lymphotrophic nanoparticle-enhanced magnetic resonance imaging (LNMRI) in identifying malignant nodal involvement in patients with renal neoplasms. METHODS MRI was performed in 9 patients with renal masses. All patients were imaged on a GE 1.5T system with phased array body coil. Protocols included T2 and T2* weighted imaging before and after administration of ferumoxtran-10 (Combidex) for the evaluation of lymph node (LN) involvement. All 9 patients underwent nephrectomy. Lymph node dissection (LND) was performed in patients with stage 2 renal cell cancer (RCC), or transitional cell cancer (TCC), per routine clinical practice. Data analysis was performed by 2 radiologists, who were blinded to pathologic results. Nodes that lacked contrast uptake were deemed malignant, and those with homogeneous uptake were deemed benign. Quantitative, retrospective analysis was performed on primary tumors by quantifying T2* with a monoexponential fitting algorithm (Osirix). T2* was quantified before, immediately after, and 24 hours after the administration of ferumoxtran-10. RESULTS MRI demonstrated 26 lymph nodes within the 9 patients imaged (24 benign and 2 malignant). Pathologic results allowed comparison in 22 of the 26 lymph nodes and demonstrated high sensitivity (100%) and specificity (95.7%). CONCLUSIONS LNMRI demonstrated high sensitivity (100%) and specificity (95.7%) in patients with renal neoplasms. Although in a relatively small sample size, the results are encouraging and warrant a larger, prospective trial. C1 [Gulmaraes, Alexander R.] Harvard Univ, Massachusetts Gen Hosp, Clin Discovery Program,Med Sch, Dept Radiol,Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Gulmaraes, AR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Clin Discovery Program,Med Sch, Dept Radiol,Ctr Mol Imaging Res, White 270,55 Fruit St, Boston, MA 02114 USA. EM aguimaraes@partners.org NR 24 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2008 VL 71 IS 4 BP 708 EP 712 DI 10.1016/j.urology.2007.11.096 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 285ZD UT WOS:000254813800039 PM 18295316 ER PT J AU Greenberg, CC Weeks, JC Stain, SC AF Greenberg, Caprice C. Weeks, Jane C. Stain, Steven C. TI Disparities in oncologic surgery SO WORLD JOURNAL OF SURGERY LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; POPULATION-BASED ANALYSIS; RACIAL-DIFFERENCES; SOCIOECONOMIC-STATUS; BREAST-CANCER; PHYSICIAN COMMUNICATION; MEDICARE BENEFICIARIES; PATIENTS PERCEPTIONS; COLORECTAL-CANCER AB Surgical oncology is one of the most frequently studied surgical specialties with regard to disparities in quality of care. There is variation in the care received according to nonclinical factors such as age, race and ethnicity, education, income, and even geographic region. Differences exist with regard to who gets treatment, what treatment is received, and the outcomes of those treatments. Although the existence of such disparities is no longer in doubt, the etiology is still being investigated. Ongoing research and quality improvement initiatives move beyond the mere description of existing disparities in one of three ways: (1) identifying and understanding the factors that lead to disparities; (2) advancing available methods to measure and track disparities; and (3) developing an approach to improvement. In this article, we start out by offering a framework to describe potential factors that lead to disparities, using examples from surgical oncology. We then describe the approaches to measuring and tracking disparities that are being used in research and quality improvement. Finally, we attempt to illustrate how all of these factors interact and offer some potential strategies to close the gap and alleviate disparities within the discipline. C1 [Greenberg, Caprice C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Greenberg, Caprice C.; Weeks, Jane C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Stain, Steven C.] Albany Med Coll, Dept Surg, Albany, NY 12208 USA. RP Greenberg, CC (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM CCGREENBERG@PARTNERS.ORG FU NCI NIH HHS [L30 CA123695] NR 47 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD APR PY 2008 VL 32 IS 4 BP 522 EP 528 DI 10.1007/s00268-007-9383-x PG 7 WC Surgery SC Surgery GA 274IW UT WOS:000253996000004 PM 18197450 ER PT J AU Wilson, C Fishman, JA Sykes, M AF Wilson, Carolyn Fishman, Jay A. Sykes, Megan TI Tribute to Eda T. Bloom, PhD SO XENOTRANSPLANTATION LA English DT Biographical-Item C1 [Wilson, Carolyn] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20014 USA. [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Infect Dis Div, Transplant Infect Dis & Compromised Hosp Program, Boston, MA USA. [Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02115 USA. RP Wilson, C (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20014 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD APR PY 2008 VL 15 IS 2 BP 69 EP 71 DI 10.1111/j.1399-3089.2008.00448.x PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 294QR UT WOS:000255421100001 ER PT J AU Tonomura, N Shimizu, A Wang, S Yamada, K Tchipashvili, V Weir, GC Yang, YG AF Tonomura, Noriko Shimizu, Akira Wang, Shumei Yamada, Kazuhiko Tchipashvili, Vaja Weir, Gordon C. Yang, Yong-Guang TI Pig islet xenograft rejection in a mouse model with an established human immune system SO XENOTRANSPLANTATION LA English DT Article DE humanized mouse model; islet; pig; xenotransplantation ID PORCINE ISLETS; IMMUNODEFICIENT MICE; CELL TRANSPLANTATION; CYNOMOLGUS MONKEYS; NONHUMAN-PRIMATES; DEPLETED MICE; MURINE MODEL; T-CELLS; SURVIVAL; MACROPHAGES AB Background: Xenotransplantation from pigs provides a potential solution to the severe shortage of human pancreata, but strong immunological rejection prevents its clinical application. A better understanding of the human immune response to pig islets would help develop effective strategies for preventing graft rejection. Methods: We assessed pig islet rejection by human immune cells in humanized mice with a functional human immune system. Humanized mice were prepared by transplantation of human fetal thymus/liver tissues and CD34(+) fetal liver cells into immunodeficient mice. Islet xenograft survival/rejection was determined by histological analysis of the grafts and measurement of porcine C-peptide in the sera of the recipients. Results: In untreated humanized mice, adult pig islets were completely rejected by 4 weeks. These mice showed no detectable porcine C-peptide in the sera, and severe intra-graft infiltration by human T cells, macrophages, and B cells, as well as deposition of human antibodies. Pig islet rejection was prevented by human T-cell depletion prior to islet xenotransplantation. Islet xenografts harvested from T-cell-depleted humanized mice were functional, and showed no human cell infiltration or antibody deposition. Conclusions: Pig islet rejection in humanized mice is largely T-cell-dependent, which is consistent with previous observations in non-human primates. These humanized mice provide a useful model for the study of human xenoimmune responses in vivo. C1 [Tonomura, Noriko; Shimizu, Akira; Wang, Shumei; Yamada, Kazuhiko; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Tchipashvili, Vaja; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01 AI 045897]; NIDDK NIH HHS [P30 DK36836] NR 29 TC 30 Z9 31 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD APR PY 2008 VL 15 IS 2 BP 129 EP 135 DI 10.1111/j.1399-3089.2008.00450.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 294QR UT WOS:000255421100017 PM 18447886 ER PT J AU Shen, F Huang, J Fitch, KR Truong, VB Kirby, A Chen, WW Zhang, J Liu, GY McCarroll, SA Jones, KW Shapero, MH AF Shen, Fan Huang, Jing Fitch, Karen R. Truong, Vivi B. Kirby, Andrew Chen, Wenwei Zhang, Jane Liu, Guoying McCarroll, Steven A. Jones, Keith W. Shapero, Michael H. TI Improved detection of global copy number variation using high density, non-polymorphic oligonucleotide probes SO BMC GENETICS LA English DT Article ID HUMAN GENOME; STRUCTURAL VARIATION; LINKAGE DISEQUILIBRIUM; SEGMENTAL DUPLICATIONS; GENOTYPING MICROARRAYS; GENE-EXPRESSION; ARRAYS; DNA; RESOLUTION; VARIANTS AB Background: DNA sequence diversity within the human genome may be more greatly affected by copy number variations (CNVs) than single nucleotide polymorphisms (SNPs). Although the importance of CNVs in genome wide association studies (GWAS) is becoming widely accepted, the optimal methods for identifying these variants are still under evaluation. We have previously reported a comprehensive view of CNVs in the HapMap DNA collection using high density 500 K EA (Early Access) SNP genotyping arrays which revealed greater than 1,000 CNVs ranging in size from 1 kb to over 3 Mb. Although the arrays used most commonly for GWAS predominantly interrogate SNPs, CNV identification and detection does not necessarily require the use of DNA probes centered on polymorphic nucleotides and may even be hindered by the dependence on a successful SNP genotyping assay. Results: In this study, we have designed and evaluated a high density array predicated on the use of nonpolymorphic oligonucleotide probes for CNV detection. This approach effectively uncouples copy number detection from SNP genotyping and thus has the potential to significantly improve probe coverage for genome-wide CNV identification. This array, in conjunction with PCR-based, complexity-reduced DNA target, queries over 1.3 M independent NspI restriction enzyme fragments in the 200 bp to 1100 bp size range, which is a several fold increase in marker density as compared to the 500 K EA array. In addition, a novel algorithm was developed and validated to extract CNV regions and boundaries. Conclusion: Using a well-characterized pair of DNA samples, close to 200 CNVs were identified, of which nearly 50% appear novel yet were independently validated using quantitative PCR. The results indicate that non-polymorphic probes provide a robust approach for CNV identification, and the increasing precision of CNV boundary delineation should allow a more complete analysis of their genomic organization. C1 [Shen, Fan; Huang, Jing; Fitch, Karen R.; Truong, Vivi B.; Chen, Wenwei; Zhang, Jane; Liu, Guoying; Jones, Keith W.; Shapero, Michael H.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Kirby, Andrew] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McCarroll, Steven A.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [McCarroll, Steven A.] Harvard Univ, Cambridge, MA 02138 USA. RP Shapero, MH (reprint author), Affymetrix Inc, 3420 Cent Expressway, Santa Clara, CA 95051 USA. EM fan_shen@affymetrix.com; jing_huang@comcast.net; karen_fitch@affymetrix.com; vivi_truong@affymetrix.com; ankirby@mac.com; joyce_chen@affymetrix.com; jane_zhang@affymetrix.com; guoying_liu@affymetrix.com; mccarroll@molbio.mgh.harvard.edu; keith_jones@affymetrix.com; michael_shapero@affymetrix.com RI McCarroll, Steven/A-8433-2009 NR 72 TC 15 Z9 16 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD MAR 28 PY 2008 VL 9 AR 27 DI 10.1186/1471-2156-9-27 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 298TR UT WOS:000255710500001 PM 18373861 ER PT J AU Lu, TC He, JC Wang, ZH Feng, X Fukumi-Tominaga, T Chen, N Xu, J Iyengar, R Klotman, PE AF Lu, Ting-chi He, John Cijiang Wang, Zhao-hui Feng, Xiaobei Fukumi-Tominaga, Tomoko Chen, Nan Xu, Jin Iyengar, Ravi Klotman, Paul E. TI HIV-1 nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNALING PATHWAY; RHO ACTIVITY; NEPHROPATHY; ACTIVATION; TYPE-1; INFECTION; RAC; ORGANIZATION; DISEASE; AIDS AB The ability of the human immunodeficiency virus, type 1 (HIV-1) protein Nef to induce cytoskeleton changes in infected host cells is a key event in viral replication. In renal podocytes, we found that Nef induced loss of stress fibers and increased lamellipodia, pathological changes leading to proteinuria in HIV-associated nephropathy. These morphological changes were mediated by Nef-induced Rac1 activation and RhoA inhibition. We identified a new interaction between Nef and diaphanous interacting protein (DIP), a recently described regulator of Rho and Rac signaling. We found that the Src homology 3 binding domain of DIP and the Nef PXXP motif were required for this interaction. Nef also interacts with Vav2 in podocytes. DIP and Vav2 both interact directly with Nef in a competitive manner. DIP interacts with p190RhoGAP, and intact DIP was required for Nef-induced phosphorylation of p190RhoGAP. DIP also interacts with Vav2, and although DIP enhanced baseline phosphorylation of Vav2, it was not required for Nef- induced Vav2 activation. In Nef- infected podocytes, Src kinase induces phosphorylation of DIP, p190RhoGAP, and Vav2, leading to RhoA inhibition and Rac1 activation. Inhibition of the Nef- induced signaling pathway by using a dominant negative of either Src or DIP or siRNA for DIP or p190RhoAGAP restored RhoA activity and stress fiber formation in Nef- infected podocytes, whereas siRNA for Vav2 reduced Rac1 activity and formation of lamellipodia. We conclude that in HIV-infected podocytes, Nef, through the recruitment of DIP and p190RhoAGAP to Nef- Src complex, activates p190RhoAGAP and down-regulates RhoA activity. C1 [Lu, Ting-chi; He, John Cijiang; Wang, Zhao-hui; Feng, Xiaobei; Klotman, Paul E.] Mt Sinai Sch Med, Div Nephrol, Dept Med, New York, NY 10029 USA. [Iyengar, Ravi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [He, John Cijiang] James J Peters Vet Affair Med Ctr, Bronx, NY 10468 USA. [Wang, Zhao-hui; Feng, Xiaobei; Chen, Nan] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Dept Nephrol, Shanghai 200025, Peoples R China. [Fukumi-Tominaga, Tomoko] Natl Inst Nat Sci, Natl Inst Physiol Sci, Sect Cell Signalling, Okazaki, Aichi 4448585, Japan. RP He, JC (reprint author), Mt Sinai Sch Med, Div Nephrol, Dept Med, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Cijiang.he@mssm.edu FU NIDDK NIH HHS [K08 DK 065495, K08 DK 079781, P01 DK 056492, R01 DK 078897]; NIGMS NIH HHS [R01 GM 54508, R01 GM054508] NR 47 TC 52 Z9 54 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 MAR 28 PY 2008 VL 283 IS 13 BP 8173 EP 8182 DI 10.1074/jbc.M708920200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278LT UT WOS:000254288000014 PM 18234668 ER PT J AU Liu, ZY Habener, JF AF Liu, Zhengyu Habener, Joel F. TI Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EMBRYONIC STEM-CELLS; DEPENDENT PROTEIN-KINASE; INSULIN-PRODUCING CELLS; TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 GENE; CAMP-RESPONSIVE ELEMENT; CYCLIN D1; REGULATES PROLIFERATION; INDEPENDENT ACTIVATION; ENDOCRINE PANCREAS; RECEPTOR AGONISTS AB The insulinotropic hormone GLP-1 (glucagon-like peptide-1) is a new therapeutic agent that preserves or restores pancreatic beta cell mass. We report that GLP-1 and its agonist, exendin-4 (Exd4), induce Wnt signaling in pancreatic beta cells, both isolated islets, and in INS-1 cells. Basal and GLP-1 agonist-induced proliferation of beta cells requires active Wnt signaling. Cyclin D1 and c-Myc, determinants of cell proliferation, are up-regulated by Exd4. Basal endogenous Wnt signaling activity depends on Wnt frizzled receptors and the protein kinases Akt and GSK3 beta but not cAMP-dependent protein kinase. In contrast, GLP-1 agonists enhance Wnt signaling via GLP-1 receptor-mediated activation of Akt and beta cell independent of GSK3 beta. Inhibition of Wnt signaling by small interfering RNAs to beta-catenin or a dominant-negative TCF7L2 decreases both basal and Exd4-induced beta cell proliferation. Wnt signaling appears to mediate GLP-1-induced beta cell proliferation raising possibilities for novel treatments of diabetes. C1 [Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,Thier 306, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [P30 DK040561-12, DK 30834, DK 55365, P30 DK 57521, P30 DK040561] NR 95 TC 159 Z9 176 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 MAR 28 PY 2008 VL 283 IS 13 BP 8723 EP 8735 DI 10.1074/jbc.M706105200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278LT UT WOS:000254288000070 PM 18216022 ER PT J AU Hoschneider, DP Scremin, OU Chialvo, DR Kay, BP Maarek, JMI AF Hoschneider, D. P. Scremin, O. U. Chialvo, D. R. Kay, B. P. Maarek, J. M. I. TI Flattened cortical maps of cerebral function in the rat: A region-of-interest approach to data sampling, analysis and display SO NEUROSCIENCE LETTERS LA English DT Article DE cerebral cortex; rats; brain mapping; topographic maps; software ID STEREOTAXIC SURGERY; VARIABILITY; BREGMA; CORTEX AB We describe a method for the measurement, analysis and display of cerebral cortical data obtained from coronal brain sections of the adult rat. In this method, regions-of-interest (ROI) are selected in the cortical mantle in a semiautomated fashion using a radial grid overlay, spaced in 15 degrees intervals from the midline. ROI measurements of intensity are mapped on a flattened two-dimensional surface. Topographic maps of statistical significance at each ROI allow for the rapid viewing of group differences. Cortical z-scores are displayed with the boundaries of brain regions defined according to a standard atlas of the rat brain. This method and accompanying software implementation (Matlab, Labview) allow for compact data display in a variety of autoradiographic and histologic studies of the structure and function of the rat brain. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Hoschneider, D. P.] Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. [Hoschneider, D. P.] Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Hoschneider, D. P.] Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Hoschneider, D. P.; Kay, B. P.; Maarek, J. M. I.] Univ So Calif, Sch Engn, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Scremin, O. U.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. [Scremin, O. U.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Chialvo, D. R.] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL USA. RP Hoschneider, DP (reprint author), Univ So Calif, Sch Med, Dept Cell & Neurobiol, 1333 San Pablo St,BMT403,MC9112, Los Angeles, CA 90033 USA. EM holschne@usc.edu RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 NR 13 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 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 28 PY 2008 VL 434 IS 2 BP 179 EP 184 DI 10.1016/j.neulet.2008.01.061 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 288EC UT WOS:000254968000006 ER PT J AU Scadden, DT AF Scadden, David T. TI Circadian rhythms - Stem cells traffic in time SO NATURE LA English DT Editorial Material ID BONE-MARROW; TISSUE C1 Harvard Univ, Stem Cell Inst, Ctr Regenerat Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Stem Cell Inst, Ctr Regenerat Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu NR 11 TC 18 Z9 19 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 27 PY 2008 VL 452 IS 7186 BP 416 EP 417 DI 10.1038/452416a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 279FU UT WOS:000254341300016 PM 18368105 ER PT J AU Yotsumoto, Y Watanabe, T Sasaki, Y AF Yotsumoto, Yuko Watanabe, Takeo Sasaki, Yuka TI Different dynamics of performance and brain activation in the time course of perceptual learning SO NEURON LA English DT Article ID SURFACE-BASED ANALYSIS; PRIMARY VISUAL-CORTEX; EVENT-RELATED FMRI; TEXTURE-DISCRIMINATION; FUNCTIONAL MRI; SLEEP; PLASTICITY; AREAS; V1 AB Perceptual learning is regarded as a manifestation of experience-dependent plasticity in the sensory systems, yet the underlying neural mechanisms remain unclear. We measured the dynamics of performance on a visual task and brain activation in the human primary visual cortex (V1) across the time course of perceptual learning. Within the first few weeks of training, brain activation in a V1 subregion corresponding to the trained visual field quadrant and task performance both increased. However, while performance levels then saturated and were maintained at a constant level, brain activation in the corresponding areas decreased to the level observed before training. These findings indicate that there are distinct temporal phases in the time course of perceptual learning, related to differential dynamics of BOLD activity in visual cortex. C1 [Yotsumoto, Yuko; Sasaki, Yuka] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Yotsumoto, Yuko; Watanabe, Takeo] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Sasaki, Yuka] CALTECH, ERATO, Shimojo Implicit Brain Funct Project, Pasadena, CA 91125 USA. [Yotsumoto, Yuko; Sasaki, Yuka] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM yuka@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41RR14075, P41 RR014075]; NEI NIH HHS [R01 EY015980, R01 EY015980-01, R01EY015980] NR 28 TC 149 Z9 155 U1 2 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 27 PY 2008 VL 57 IS 6 BP 827 EP 833 DI 10.1016/j.neuron.2008.02.034 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 281LV UT WOS:000254500000007 PM 18367084 ER PT J AU Levine, S Nguyen, T Taylor, N Friscia, ME Budak, MT Rothenberg, P Zhu, JL Sachdeva, R Sonnad, S Kaiser, LR Rubinstein, NA Powers, SK Shrager, JB AF Levine, Sanford Nguyen, Taitan Taylor, Nyali Friscia, Michael E. Budak, Murat T. Rothenberg, Pamela Zhu, Jianliang Sachdeva, Rajeev Sonnad, Seema Kaiser, Larry R. Rubinstein, Neal A. Powers, Scott K. Shrager, Joseph B. TI Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; UBIQUITIN-PROTEASOME PATHWAY; SKELETAL-MUSCLE; OXIDATIVE STRESS; INJURY; MECHANISMS; EXPRESSION; CYTOKINES; FAILURE; MYOSIN AB Background: The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm. Methods: We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). Case subjects had diaphragmatic inactivity and underwent mechanical ventilation for 18 to 69 hours; among control subjects diaphragmatic inactivity and mechanical ventilation were limited to 2 to 3 hours. We carried out histologic, biochemical, and gene-expression studies on these specimens. Results: As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P=0.001) and 53% (P=0.01), respectively, decreased glutathione concentration of 23% (P=0.01), increased active caspase-3 expression of 100% (P=0.05), a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P=0.002), and a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P=0.001). Conclusions: The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity. C1 [Levine, Sanford; Nguyen, Taitan; Taylor, Nyali; Friscia, Michael E.; Budak, Murat T.; Rothenberg, Pamela; Zhu, Jianliang; Sonnad, Seema; Kaiser, Larry R.; Shrager, Joseph B.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Rubinstein, Neal A.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Levine, Sanford; Budak, Murat T.; Rubinstein, Neal A.; Shrager, Joseph B.] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA. [Levine, Sanford] Gift Life Donor Program, Philadelphia, PA USA. [Levine, Sanford; Nguyen, Taitan; Sachdeva, Rajeev; Shrager, Joseph B.] Dept Vet Affairs Med Ctr, Med Res Surg & Lab Med Serv, Philadelphia, PA 19104 USA. [Powers, Scott K.] Univ Florida, Ctr Exercise Sci, Gainesville, FL 32611 USA. RP Levine, S (reprint author), 1495 Wesleys Run, Gladwyne, PA 19035 USA. EM sdlevine@mail.med.upenn.edu RI Budak, Murat/I-8358-2013 OI Budak, Murat/0000-0002-5059-9651 FU NHLBI NIH HHS [R01-HL-078834] NR 29 TC 479 Z9 507 U1 2 U2 23 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 MAR 27 PY 2008 VL 358 IS 13 BP 1327 EP 1335 DI 10.1056/NEJMoa070447 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 278TE UT WOS:000254308400003 PM 18367735 ER PT J AU Haver, KE Hartnick, CJ Ryan, DP Shailam, R Mark, EJ Pasternack, MS Pilch, BZ Harris, NL AF Haver, Kenan E. Hartnick, Christopher J. Ryan, Daniel P. Shailam, Randheer Mark, Eugene J. Pasternack, Mark S. Pilch, Ben Z. Harris, Nancy Lee TI A girl with dyspnea on exertion - Glomus tumor of the trachea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 [Haver, Kenan E.] Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. [Ryan, Daniel P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Shailam, Randheer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Haver, Kenan E.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Ryan, Daniel P.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Shailam, Randheer] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Haver, KE (reprint author), Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. NR 18 TC 5 Z9 5 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 MAR 27 PY 2008 VL 358 IS 13 BP 1382 EP 1390 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 278TE UT WOS:000254308400011 PM 18367742 ER PT J AU Molli, PR Singh, RR Lee, SW Kumar, R AF Molli, P. R. Singh, R. R. Lee, S. W. Kumar, R. TI MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene SO ONCOGENE LA English DT Article DE NURD complex; chromatin remodeling centrosome; aneuploidy ID SPORADIC BREAST-CANCER; CENTROSOME AMPLIFICATION; CELL-CYCLE; ESTROGEN-RECEPTOR; DOWN-REGULATION; MTA1 GENE; PROTEIN; INSTABILITY; EXPRESSION; COMPLEX AB Metastasis-associated tumor antigen 1 (MTA1), a component of the nucleosome remodeling and deacetylating (NuRD) complex is routinely upregulated in several cancers. In the present study, we investigated the potential role of MTA1 in BRCA1 transcriptional repression and subsequent chromosomal instability. MTA1-NuRD complex was found to negatively regulate BRCA1 transcription by physically associating with an atypical estrogen-responsive element (ERE) on the BRCA1 promoter. Moreover, MTA1 and HDAC complex recruited to the ERE of BRCA1 promoter in an ER a-dependent manner. Accordingly, BRCA1 protein levels were enhanced by silencing of either MTA1 expression or by treatment with the specific histone deacetylase inhibitor trichostatin A. MTA1's strong repressive effects on BRCA1 expression was supported by our observation that cells stably overexpressing MTA1 showed centrosome amplification which has been long implicated as a phenotype for BRCA1 repression. Accordingly, overexpression of BRCA1 in cells stably over expressing MTA1 resulted in restoration of normal centrosome numbers. Together, these findings strongly implicate MTA1 in the transcriptional repression of BRCA1 leading to abnormal centrosome number and chromosomal instability. C1 [Molli, P. R.; Singh, R. R.; Kumar, R.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. [Lee, S. W.] Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA USA. [Kumar, R.] Baylor Coll Med, Houston, TX USA. RP Kumar, R (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM rkumar@mdanderson.org FU NCI NIH HHS [U01 CA065746, CA 098823, CA65746, R01 CA065746, R01 CA065746-05, R01 CA098823, R01 CA098823-04] NR 34 TC 46 Z9 53 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 27 PY 2008 VL 27 IS 14 BP 1971 EP 1980 DI 10.1038/sj.onc.1210839 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 279MK UT WOS:000254359100002 PM 17922032 ER PT J AU Lobanova, ES Finkelstein, S Herrmann, R Chen, YM Kessler, C Michaud, NA Trieu, LH Strissel, KJ Burns, ME Arshavsky, VY AF Lobanova, Ekaterina S. Finkelstein, Stella Herrmann, Rolf Chen, Yen-Ming Kessler, Christopher Michaud, Norman A. Trieu, Lynn H. Strissel, Katherine J. Burns, Marie E. Arshavsky, Vadim Y. TI Transducin gamma-subunit sets expression levels of alpha- and beta-subunits and is crucial for rod viability SO JOURNAL OF NEUROSCIENCE LA English DT Article DE transducin; photoreceptor; G-proteins; cell death; protein expression; protein localization ID LIGHT-DRIVEN TRANSLOCATION; GTPASE-ACTIVATING COMPLEX; PHOSDUCIN-LIKE PROTEIN; RETINAL RODS; VERTEBRATE PHOTORECEPTORS; RETINITIS-PIGMENTOSA; KNOCKOUT MOUSE; ADAPTATION; PHOTOTRANSDUCTION; MICE AB Transducin is a prototypic heterotrimeric G-protein mediating visual signaling in vertebrate photoreceptor cells. Despite its central role in phototransduction, little is known about the mechanisms that regulate its expression and maintain approximately stoichiometric levels of the alpha- and beta gamma-subunits. Here we demonstrate that the knock-out of transducin gamma-subunit leads to a major downregulation of both alpha- and beta-subunit proteins, despite nearly normal levels of the corresponding transcripts, and fairly rapid photoreceptor degeneration. Significant fractions of the remaining alpha- and beta-subunits were mislocalized from the light-sensitive outer segment compartment of the rod. Yet, the tiny amount of the alpha-subunit present in the outer segments of knock-out rods was sufficient to support light signaling, although with a markedly reduced sensitivity. These data indicate that the gamma-subunit controls the expression level of the entire transducin heterotrimer and that heterotrimer formation is essential for normal transducin localization. They further suggest that the production of transducin beta-subunit without its constitutive gamma-subunit partner sufficiently stresses the cellular biosynthetic and/or chaperone machinery to induce cell death. C1 [Lobanova, Ekaterina S.; Finkelstein, Stella; Herrmann, Rolf; Arshavsky, Vadim Y.] Duke Univ, Ctr Eye, Albert Eye Res Inst, Durham, NC 27710 USA. [Chen, Yen-Ming; Kessler, Christopher; Burns, Marie E.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95618 USA. [Chen, Yen-Ming; Kessler, Christopher; Burns, Marie E.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95618 USA. [Michaud, Norman A.; Trieu, Lynn H.; Strissel, Katherine J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Duke Univ, Ctr Eye, Albert Eye Res Inst, 5008 AERI,2351 Erwin Rd, Durham, NC 27710 USA. EM vadim.arshavsky@duke.edu FU NEI NIH HHS [EY10336, EY 14047, EY5722, P30 EY005722, P30 EY005722-22, R01 EY010336, R01 EY010336-16, R01 EY014047, R01 EY014047-07] NR 53 TC 48 Z9 50 U1 0 U2 0 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 MAR 26 PY 2008 VL 28 IS 13 BP 3510 EP 3520 DI 10.1523/JNEUROSCI.0338-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 279WT UT WOS:000254386600026 PM 18367617 ER PT J AU Lal, A Kim, HH Abdelmohsen, K Kuwano, Y Pullmann, R Srikantan, S Subrahmanyam, R Martindale, JL Yang, XL Ahmed, F Navarro, F Dykxhoorn, D Lieberman, J Gorospe, M AF Lal, Ashish Kim, Hyeon Ho Abdelmohsen, Kotb Kuwano, Yuki Pullmann, Rudolf Srikantan, Subramanya Subrahmanyam, Ramesh Martindale, Jennifer L. Yang, Xiaoling Ahmed, Fariyal Navarro, Francisco Dykxhoorn, Derek Lieberman, Judy Gorospe, Myriam TI p16(INK4a) Translation Suppressed by miR-24 SO PLOS ONE LA English DT Article AB Background: Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence. Methodology/Principal Findings: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3'-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS)-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites. Conclusions/Significance: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation. C1 [Lal, Ashish; Kim, Hyeon Ho; Abdelmohsen, Kotb; Kuwano, Yuki; Pullmann, Rudolf; Srikantan, Subramanya; Subrahmanyam, Ramesh; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, IRP, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Lal, Ashish; Ahmed, Fariyal; Navarro, Francisco; Dykxhoorn, Derek; Lieberman, Judy] Harvard Med Sch, CBR Inst Biomed Res, Dept Pediat, Boston, MA USA. RP Lal, A (reprint author), NIA, IRP, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM alal@cbrinstitute.org; myriam-gorospe@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012; Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015; OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU National Institute on Aging - Intramural Research Program FX National Institute on Aging - Intramural Research Program NR 40 TC 148 Z9 157 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 26 PY 2008 VL 3 IS 3 AR e1864 DI 10.1371/journal.pone.0001864 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370KZ UT WOS:000260762400023 PM 18365017 ER PT J AU Weyman, AE AF Weyman, Arthur E. TI The year in echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIAC RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR DYSSYNCHRONY; DIASTOLIC HEART-FAILURE; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; PATENT FORAMEN OVALE; MITRAL REGURGITATION; STRESS ECHOCARDIOGRAPHY; NARROW QRS; SYSTOLIC ASYNCHRONY; EJECTION FRACTION C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 25 PY 2008 VL 51 IS 12 BP 1221 EP 1229 DI 10.1016/j.jacc.2008.01.018 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 277MO UT WOS:000254217000012 PM 18355662 ER PT J AU Arany, Z Wagner, BK Ma, Y Chinsomboon, J Laznik, D Spiegelman, BM AF Arany, Zoltan Wagner, Bridget K. Ma, Yanhong Chinsomboon, Jessica Laznik, Dina Spiegelman, Bruce M. TI Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1 alpha and oxidative phosphorylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE colchicine; high throughput ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; ACTIVATED PROTEIN-KINASE; PPAR-GAMMA COACTIVATOR-1; SKELETAL-MUSCLE; HIGH-THROUGHPUT; HEPATIC GLUCONEOGENESIS; PGC-1; EXERCISE; HOMEOSTASIS; PATHWAYS AB The transcriptional coactivator PGC-1 alpha is a potent regulator of several metabolic pathways, including, in particular, the activation of oxidative phosphorylation and mitochondrial biogenesis. Recent evidence suggests that increasing PGC-1 alpha activity may have beneficial effects in various conditions, including muscular dystrophy, diabetes, and neurodegenerative diseases. We describe here a high-throughput screen to identify small molecules that induce PGC-1 alpha expression in skeletal muscle cells. A number of drug classes are identified, including glucocorticoids, microtubule inhibitors, and protein synthesis inhibitors. These drugs induce PGC-1 alpha mRNA, and the expression of a number of genes known to be regulated by PGC-1 alpha. No induction of these target genes is seen in PGC-1 alpha -/- cells, demonstrating that the drugs act through PGC-1 alpha. These data demonstrate the feasibility of high-throughput screening for inducers of PGC-1 alpha. Moreover, the data identify microtubule inhibitors and protein synthesis inhibitors as modulators of PGC-1 alpha and oxidative phosphorylation. C1 [Arany, Zoltan; Ma, Yanhong; Chinsomboon, Jessica; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Arany, Zoltan; Ma, Yanhong; Chinsomboon, Jessica; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Arany, Zoltan] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Wagner, Bridget K.] Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA. [Arany, Zoltan] Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NHLBI NIH HHS [K08 HL079172, HL079172]; NIDDK NIH HHS [DK61562, R24 DK080261, R56 DK054477, R01 DK061562, DK54477, R01 DK054477]; NINDS NIH HHS [R21 NS059440, NS059440] NR 42 TC 56 Z9 57 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 25 PY 2008 VL 105 IS 12 BP 4721 EP 4726 DI 10.1073/pnas.0800979105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285JI UT WOS:000254772700035 PM 18347329 ER PT J AU Jia, YH Loison, F Hattori, H Li, YT Erneux, C Park, SY Gao, C Chai, L Silberstein, LE Schurmans, S Luo, HB AF Jia, Yonghui Loison, Fabien Hattori, Hidenori Li, Yitang Erneux, Christophe Park, Shin-Young Gao, Chong Chai, Li Silberstein, Leslie E. Schurmans, Stephane Luo, Hongbo R. TI Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematopoiesis; inositol phosphate; neutrophils ID INOSITOL 1,3,4,5-TETRAKISPHOSPHATE; EXPRESSION; 3-KINASE; PROTEIN; CLONING; CELLS; PHOSPHORYLATION; IDENTIFICATION; NEUTROPHILS; CHEMOTAXIS AB Inositol trisphosphate 3-kinase B (InsP3KB) belongs to a family of kinases that convert inositol 1,4,5-trisphosphate (Ins(1,4,5)P3 or IP3) to inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4). Previous studies have shown that disruption of InsP3KB leads to impaired T cell and B cell development as well as hyperactivation of neutrophils. Here, we demonstrate that InsP3KB is also a physiological modulator of myelopoiesis. The InsP3KB gene is expressed in all hematopoietic stem/progenitor cell populations. In InsP3KB null mice, the bone marrow granulocyte monocyte progenitor (GMP) population was expanded, and GMP cells proliferated significantly faster. Consequently, neutrophil production in the bone marrow was enhanced, and the peripheral blood neutrophil count was also substantially elevated in these mice. These effects might be due to enhancement of PtdIns(3,4,5)P3/Akt signaling in the InsP3KB null cells. Phosphorylation of cell cycle-inhibitory protein p21(cip1), one of the downstream targets of Akt, was augmented, which can lead to the suppression of the cell cycle-inhibitory effect of p21. C1 [Jia, Yonghui; Loison, Fabien; Hattori, Hidenori; Li, Yitang; Park, Shin-Young; Silberstein, Leslie E.; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Luo, Hongbo R.] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Lab Med, Childrens Hosp, Boston, MA 02115 USA. [Jia, Yonghui; Loison, Fabien; Hattori, Hidenori; Li, Yitang; Park, Shin-Young; Gao, Chong; Chai, Li; Silberstein, Leslie E.; Luo, Hongbo R.] Harvard Univ, Sch Med, Joint Program Transfus Med, Boston, MA 02115 USA. [Erneux, Christophe; Schurmans, Stephane] Univ Libre Bruxelles, Inst Rech Interdisciplinaire & Biol Humaine & Mol, B-6041 Gosselies, Belgium. RP Luo, HB (reprint author), Karp Family Res Bldg,Room 10214, Boston, MA 02115 USA. EM hongbo.luo@childrens.harvard.edu RI Loison, Fabien/G-3385-2014 OI Loison, Fabien/0000-0002-6678-1730 FU NHLBI NIH HHS [HL085100, R01 HL085100, R01 HL092437]; NIDDK NIH HHS [P01 DK080665]; NIGMS NIH HHS [R01 GM076084, GM076084] NR 21 TC 19 Z9 20 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 25 PY 2008 VL 105 IS 12 BP 4739 EP 4744 DI 10.1073/pnas.0800218105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285JI UT WOS:000254772700038 PM 18339802 ER PT J AU Campanella, GSV Tager, AM El Khoury, JK Thomas, SY Abrazinski, TA Manice, LA Colvin, RA Lustert, AD AF Campanella, Gabriele S. V. Tager, Andrew M. El Khoury, Joseph K. Thomas, Seddon Y. Abrazinski, Tabitha A. Manice, Lindsay A. Colvin, Richard A. Lustert, Andrew D. TI Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T cells; plasmodium; IP-10; brain; trafficking ID T-CELL TRAFFICKING; CEREBROSPINAL-FLUID; IP-10; RECRUITMENT; DEFICIENCY; INFECTION; MORTALITY; CHILDREN; BRAIN; HOST AB Cerebral malaria is a significant cause of global mortality, causing an estimated two million deaths per year, mainly in children. The pathogenesis of this disease remains incompletely understood. Chemokines have been implicated in the development of cerebral malaria, and the IFN-inducible CXCR3 chemokine ligand IP-10 (CXCL10) was recently found to be the only serum biomarker that predicted cerebral malaria mortality in Ghanaian children. We show that the CXCR3 chemokine ligands IP-10 and Mig (CXCL9) were highly induced in the brains of mice with murine cerebral malaria caused by Plasmodium berghei ANKA. Mice deficient in CXCR3 were markedly protected against cerebral malaria and had far fewer T cells in the brain compared with wild-type mice. In competitive transfer experiments, CXCR3-deficient CD8(+) T cells were 7-fold less efficient at migrating into the infected brains than wild-type CD8+ T cells. Adoptive transfer of wild-type CD8+ effector T cells restored susceptibility of CXCR3-deficient mice to cerebral malaria and also restored brain proinflammatory cytokine and chemokine production and recruitment of T cells, independent of CXCR3. Mice deficient in IP-10 or Mig were both partially protected against cerebral malaria mortality when infected with P. berghei ANKA. Brain immunohistochemistry revealed Mig staining of endothelial cells, whereas IP-10 staining was mainly found in neurons. These data demonstrate that CXCR3 on CD8+ T cells is required for T cell recruitment into the brain and the development of murine cerebral malaria and suggest that the CXCR3 ligands Mig and IP-10 play distinct, nonredundant roles in the pathogenesis of this disease. C1 [Campanella, Gabriele S. V.; Tager, Andrew M.; El Khoury, Joseph K.; Thomas, Seddon Y.; Abrazinski, Tabitha A.; Manice, Lindsay A.; Colvin, Richard A.; Lustert, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Charlestown, MA 02129 USA. RP Lustert, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NCI NIH HHS [R01 CA069212, R01-CA69212] NR 19 TC 139 Z9 142 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 25 PY 2008 VL 105 IS 12 BP 4814 EP 4819 DI 10.1073/pnas.0801544105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285JI UT WOS:000254772700051 PM 18347328 ER PT J AU Silva, SS Rowntree, RK Mekhoubad, S Lee, JT AF Silva, Susana S. Rowntree, Rebecca K. Mekhoubad, Shila Lee, Jeannie T. TI X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN BLASTOCYSTS; CELLULAR-DIFFERENTIATION; LINES; GENE; MAINTENANCE; EXPRESSION; CULTURE; TUMORS; TSIX AB With the potential to give rise to all somatic cell types, human embryonic stem cells (hESC) have generated enormous interest as agents of cell replacement therapy. One potential limitation is their safety in vivo. Although several studies have focused on concerns over genomic stability ex vivo, few have analyzed epigenetic stability. Here, we use tools of the epigenetic phenomenon, X-chromosome inactivation (XCI), to investigate their epigenetic properties. Among 11 distinct hESC lines, we find a high degree of variability. We show that, like mouse ESC, hESC in principle have the capacity to recapitulate XCI when induced to differentiate in culture (class I lines). However, this capacity is seen in few hESC isolates. Many hESC lines have already undergone XCI (class II and III). Unexpectedly, there is a tendency to lose XIST RNA expression during culture (class III). Despite losing H3-K27 trimethylation, the inactive X of class III lines remains transcriptionally suppressed, as indicated by Cot-1 RNA exclusion. We conclude that hESC lines are subject to dynamic epigenetic reprogramming ex vivo. Given that XCI and cell differentiation are tightly linked, we consider implications for hESC pluripotency and differentiation potential. C1 [Silva, Susana S.; Rowntree, Rebecca K.; Mekhoubad, Shila; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Silva, Susana S.; Rowntree, Rebecca K.; Mekhoubad, Shila; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Biol Mol, Boston, MA 02114 USA. [Silva, Susana S.] Gulbenkian Inst Sci, Gulbenkian Phd Programme Biomed, P-2780156 Oeiras, Portugal. [Mekhoubad, Shila] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Biol Mol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute; NIGMS NIH HHS [R01-GM58839-S1, R01 GM058839] NR 25 TC 167 Z9 171 U1 2 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 MAR 25 PY 2008 VL 105 IS 12 BP 4820 EP 4825 DI 10.1073/pnas.0712136105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285JI UT WOS:000254772700052 PM 18339803 ER PT J AU Arboleda-Velasquez, JF Zhou, Z Shin, HK Louvi, A Kim, HH Savitz, SI Liao, JK Salomone, S Ayata, C Moskowitz, MA Artavanis-Tsakonas, S AF Arboleda-Velasquez, Joseph F. Zhou, Zhipeng Shin, Hwa Kyoung Louvi, Angeliki Kim, Hyung-Hwan Savitz, Sean I. Liao, James K. Salomone, Salvatore Ayata, Cenk Moskowitz, Michael A. Artavanis-Tsakonas, Spyros TI Linking Notch signaling to ischemic stroke SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ischemia; Notch3; vascular smooth muscle; CADASIL ID NITRIC-OXIDE SYNTHASE; NOTCH3-DEFICIENT MICE; EXPRESSION; CADASIL; CELLS; DEPOLARIZATIONS; GALACTOSIDASE; DEMENTIA; INFARCTS; CORTEX AB Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology of stroke, the third most common cause of death and the leading cause of long-term neurological disability in the world. However, there is little insight into the underlying cellular pathways that link SMC function to brain ischemia susceptibility. Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. C1 [Arboleda-Velasquez, Joseph F.; Artavanis-Tsakonas, Spyros] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Zhou, Zhipeng; Shin, Hwa Kyoung; Savitz, Sean I.; Salomone, Salvatore; Ayata, Cenk; Moskowitz, Michael A.] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. [Louvi, Angeliki] Yale Univ, Sch Med, Program Neurogent, New Haven, CT 06520 USA. [Savitz, Sean I.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. [Kim, Hyung-Hwan; Liao, James K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA. [Artavanis-Tsakonas, Spyros] Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM artavanis@hms.harvard.edu RI Moskowitz, Michael/D-9916-2011; OI Salomone, Salvatore/0000-0001-5307-6103 FU NCI NIH HHS [CA098402-06, R01 CA098402]; NHGRI NIH HHS [HG003616-01A1, R01 HG003616]; NHLBI NIH HHS [R01 HL052233, HL052233]; NINDS NIH HHS [5 P50 NS10828-32, NS026084-18, P50 NS010828, R01 NS026084, R37 NS026084] NR 29 TC 51 Z9 51 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 25 PY 2008 VL 105 IS 12 BP 4856 EP 4861 DI 10.1073/pnas.0709867105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285JI UT WOS:000254772700058 PM 18347334 ER PT J AU Henrickson, SE Mempel, TR Mazo, IB Liu, B Artyomov, MN Zheng, H Peixoto, A Flynn, M Senman, B Junt, T Wong, HC Chakraborty, AK von Andrian, UH AF Henrickson, Sarah E. Mempel, Thorsten R. Mazo, Irina B. Liu, Bai Artyomov, Maxim N. Zheng, Huan Peixoto, Antonio Flynn, Michael Senman, Balimkiz Junt, Tobias Wong, Hing C. Chakraborty, Arup K. von Andrian, Ulrich H. TI In Vivo Imaging of T Cell Priming SO SCIENCE SIGNALING LA English DT Article AB The rules by which naive T cells decide whether and how to respond to antigenic stimuli are incompletely understood. Using multiphoton intravital microscopy (MP-IVM) in lymphnodes (LNs), we have shown that CD8(+) T cells are primed by antigen-presenting dendritic cells (DCs) in three consecutive phases. During phaseone, T cells undergo brief serial contacts with many DCs for several hours after homing in to the LNs. Subsequently, during phase two, T cells engage in prolonged stable interactions with DCs. Finally, in the third phase, T cells return to transient interactions with DCs as they begin to proliferate and eventually leave the LNs. We have examined the influence of antigen dose on the duration of phase one by systematically varying both the number of cognate peptide-major his to compatability (pMHC) complexes per DC and the density of cognate pMHC complex-presenting DCs per LN. The duration of phase one and the kinetics of CD8+ T cell activation were inversely correlated with both parameters. Very few pMHC complexes were needed for full T cell activation and effect or differentiation. Further more, there was a sharp threshold of antigen dose below which T cells did not transition to phase two but continued to migrate until they exited the LN, unactivated. The stability of peptide binding to MHC was a critical determinant of this threshold antigen dose in vivo. Our results suggest an integrative mechanism that allows T cells to reach an informed decision about whether to respond, based on the over all antigen dose encountered. C1 [Henrickson, Sarah E.; Mempel, Thorsten R.; Mazo, Irina B.; Peixoto, Antonio; Flynn, Michael; Senman, Balimkiz; Junt, Tobias; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Henrickson, Sarah E.; Mempel, Thorsten R.; Mazo, Irina B.; Peixoto, Antonio; Flynn, Michael; Senman, Balimkiz; Junt, Tobias; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Liu, Bai; Wong, Hing C.] Altor BioSci Corp, Miramar, FL 33025 USA. [Artyomov, Maxim N.; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Zheng, Huan; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NIGMS NIH HHS [T32 GM007753] NR 7 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAR 25 PY 2008 VL 1 IS 12 AR pt2 DI 10.1126/stke.112pt2 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10VD UT WOS:000207490600004 PM 18364513 ER PT J AU Newsome, BB Warnock, DG McClellan, WM Herzog, CA Kiefe, CI Eggers, PW Allison, JJ AF Newsome, Britt B. Warnock, David G. McClellan, William M. Herzog, Charles A. Kiefe, Catarina I. Eggers, Paul W. Allison, Jeroan J. TI Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol ID ACUTE KIDNEY INJURY; COOPERATIVE CARDIOVASCULAR PROJECT; QUALITY-OF-CARE; REPLACEMENT THERAPY; MEDICARE PATIENTS; INTENSIVE-CARE; HEART-FAILURE; OUTCOMES; POPULATION; PROGNOSIS AB Background: Although small changes in creatinine level during hospitalization have been associated with risk of short-term mortality, associations with posthospitalization end-stage renal disease (ESRD) and long-term mortality are unknown. We assessed the relationship between change in serum creatinine levels up to 3.0 mg/dL and death and ESRD among elderly survivors of hospitalization for acute myocardial infarction. Methods: Retrospective cohort study of a nationally representative sample of Medicare beneficiaries admitted with acute myocardial infarction to nonfederal US hospitals between February 1994 and July 1995. Outcomes were mortality and ESRD through June 2004. Results: The 87 094 eligible patients admitted to 4473 hospitals had a mean age of 77.1 years; for the 43.2% with some creatinine increase, quartiles of increase were 0.1, 0.2, 0.3 to 0.5, and 0.6 to 3.0 mg/dL. Incidence of ESRD and mortality ranged from 2.3 and 139.1 cases per 1000 person-years, respectively, among patients with no increase to 20.0 and 274.9 cases per 1000 person-years in the highest quartile of creatinine increase. Compared with patients without creatinine increase, adjusted hazard ratios by quartile of increase were 1.45, 1.97, 2.36, and 3.26 for ESRD and 1.14, 1.16, 1.26, and 1.39 for mortality, with no 95% confidence intervals overlapping 1.0 for,either end point. Conclusion: In a nationally representative sample of elderly patients discharged after hospitalization for acute myocardial infarction, small changes in serum creatinine level during hospitalization were associated with an independent higher risk of ESRD and death. C1 [Newsome, Britt B.; Warnock, David G.] Univ Alabama, Div Nephrol, Birmingham, AL 35294 USA. [Newsome, Britt B.; Kiefe, Catarina I.; Allison, Jeroan J.] Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. [Allison, Jeroan J.] Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. [Newsome, Britt B.; Kiefe, Catarina I.; Allison, Jeroan J.] Univ Alabama, Ctr Nephrol Res & Training, Dept Med, Birmingham, AL 35294 USA. [Kiefe, Catarina I.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [McClellan, William M.] Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA 30322 USA. [Herzog, Charles A.] US Renal Data Syst, Cardiovasc Special Studies Ctr, Minneapolis, MN USA. [Eggers, Paul W.] NIDDKD, Bethesda, MD 20892 USA. RP Newsome, BB (reprint author), Univ Alabama, Div Nephrol, 1530 3rd Ave,S Room 524, Birmingham, AL 35294 USA. OI Allison, Jeroan/0000-0003-4472-2112 NR 59 TC 150 Z9 156 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 2008 VL 168 IS 6 BP 609 EP 616 DI 10.1001/archinte.168.6.609 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 277UY UT WOS:000254241400009 PM 18362253 ER PT J AU Murff, HJ Peterson, NB Fowke, JH Hargreaves, M Signorello, LB Dittus, RS Zheng, W Blot, WJ AF Murff, Harvey J. Peterson, Neeraja B. Fowke, Jay H. Hargreaves, Margaret Signorello, Lisa B. Dittus, Robert S. Zheng, Wei Blot, William J. TI Colonoscopy screening in African Americans and whites with affected first-degree relatives SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CANCER TEST USE; COLORECTAL-CANCER; COLON-CANCER; ADENOMATOUS POLYPS; FAMILY-HISTORY; RISK; SURVEILLANCE; INDIVIDUALS; POPULATION; US AB Background: Family history is a risk factor for colon cancer, and guidelines recommend initiating screening at age 40 years in individuals with affected relatives. Racial differences in colon cancer mortality could be related to variations in screening of increased-risk individuals. Methods: Baseline data from 41830 participants in the Southern Community Cohort Study were analyzed to determine the proportion of colonoscopy procedures in individuals with strong family histories of colon cancer, and whether differences existed based on race. Results: In participants with multiple affected first-degree relatives (FDRs) or relatives diagnosed before age 50 years, 27.3% (95% confidence interval [CI], 23.5%31.1%) of African Americans reported having a colonoscopy within the past 5 years compared with 43.1% (95% CI, 37.0%-49.2%) of white participants (P <.001). African Americans in this group had an odds ratio of 0.51 (95% CI, 0.38-0.68) of having undergone recommended screening procedures compared with white participants after adjusting for age, sex, educational status, annual income, insurance status, total number of affected and unaffected FDRs, and time since last medical visit. African Americans with multiple affected FDRs or relatives diagnosed before age 50 years and who had ever undergone endoscopy were less likely to report a personal history of colon polyps (odds ratio, 0.29; 95% CI, 0.20-0.42) when compared with whites with similar family histories. Conclusions: African Americans who have FDRs with colon cancer are less likely to undergo colonoscopy screening compared with whites who have affected relatives. Increased efforts need to be directed at identifying and managing underserved populations at increased risk for colon cancer based on their family histories. C1 [Murff, Harvey J.] Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN 37203 USA. [Fowke, Jay H.; Zheng, Wei; Blot, William J.] Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA. [Murff, Harvey J.; Peterson, Neeraja B.; Fowke, Jay H.; Signorello, Lisa B.; Dittus, Robert S.; Zheng, Wei; Blot, William J.] Vanderbilt Univ, Dept Med, Div Gen Internal Med & Publ Hlth, Nashville, TN USA. [Murff, Harvey J.; Peterson, Neeraja B.; Fowke, Jay H.; Signorello, Lisa B.; Zheng, Wei; Blot, William J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Murff, Harvey J.; Dittus, Robert S.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. [Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. RP Murff, HJ (reprint author), Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, 2525 W End Ave, Nashville, TN 37203 USA. EM harvey.j.murff@vanderbilt.edu FU NCI NIH HHS [K07 CA114029-03, P50 CA095103, CA092447, CA114029, K07 CA114029, R01 CA092447] NR 35 TC 21 Z9 21 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 2008 VL 168 IS 6 BP 625 EP 631 DI 10.1001/archinte.168.6.625 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 277UY UT WOS:000254241400011 PM 18362255 ER PT J AU Pui, CH Robison, LL Look, AT AF Pui, Ching-Hon Robison, Leslie L. Look, A. Thomas TI Acute lymphoblastic leukaemia SO LANCET LA English DT Review ID CHILDRENS-CANCER-GROUP; STEM-CELL TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOCYTIC-LEUKEMIA; ESCHERICHIA-COLI-ASPARAGINASE; MULTICENTER RANDOMIZED-TRIAL; TRANSGENIC ZEBRAFISH MODEL; GENE-EXPRESSION SIGNATURES; TRAUMATIC LUMBAR PUNCTURE; PEDIATRIC-ONCOLOGY-GROUP AB Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-firee survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease. Meanwhile, studies are underway to ascertain the precise events that take place in the genesis of acute lymphoblastic leukaemia, to enhance the clinical application of known risk factors and antileukaemic agents, and to identify treatment regimens that might boost the generally low cure rates in adults and subgroups of children with high-risk leukaemia. C1 [Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Univ Tennessee, Memphis, TN USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Boston, MA USA. RP Pui, CH (reprint author), St Jude Childrens Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM ching-hon.pui@stjude.org FU NCI NIH HHS [CA52259, CA06516, CA21765, CA36401, CA51001, CA60419, CA68484, CA78224, CA90246, P30 CA006516]; NIGMS NIH HHS [GM61393]; NINR NIH HHS [NR07610] NR 171 TC 648 Z9 698 U1 17 U2 90 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 22 PY 2008 VL 371 IS 9617 BP 1030 EP 1043 DI 10.1016/S0140-6736(08)60457-2 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 277IN UT WOS:000254206000031 PM 18358930 ER PT J AU Lupien, M Eeckhoute, J Meyer, CA Wang, QB Zhang, Y Li, W Carroll, JS Liu, XS Brown, M AF Lupien, Mathieu Eeckhoute, Jerome Meyer, Clifford A. Wang, Qianben Zhang, Yong Li, Wei Carroll, Jason S. Liu, X. Shirley Brown, Myles TI FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription SO CELL LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; CELL-CYCLE PROGRESSION; BREAST-CANCER; GENE-EXPRESSION; BINDING-SITES; HUMAN GENOME; CHROMATIN SIGNATURES; COMPACTED CHROMATIN; ANDROGEN RECEPTOR; LOCATION ANALYSIS AB Complex organisms require tissue-specific transcriptional programs, yet little is known about how these are established. The transcription factor FoxA1 is thought to contribute to gene regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific functions rely primarily on differential recruitment to chromatin predominantly at distant enhancers rather than proximal promoters. This differential recruitment leads to cell type-specific changes in chromatin structure and functional collaboration with lineage-specific transcription factors. Despite the ability of FoxA1 to bind nucleosomes, its differential binding to chromatin sites is dependent on the distribution of histone H3 lysine 4 dimethylation. Together, our results suggest that methylation of histone H3 lysine 4 is part of the epigenetic signature that defines lineage-specific FoxA1 recruitment sites in chromatin. FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs. C1 [Lupien, Mathieu; Eeckhoute, Jerome; Wang, Qianben; Carroll, Jason S.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Lupien, Mathieu; Eeckhoute, Jerome; Wang, Qianben; Carroll, Jason S.; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lupien, Mathieu; Eeckhoute, Jerome; Wang, Qianben; Carroll, Jason S.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyer, Clifford A.; Zhang, Yong; Li, Wei; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meyer, Clifford A.; Zhang, Yong; Li, Wei; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Li, Wei/A-8544-2009; Zhang, Yong/B-4838-2011; Wang, Qianben/E-4267-2011; OI Zhang, Yong/0000-0001-6316-2734; Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NCI NIH HHS [P01 CA080111, P01 CA080111-010002, P01 CA080111-060002, P01 CA080111-070002, P01 CA080111-080002, P01 CA080111-090002, P01 CA080111-100002, P01 CA8011105, P50 CA089393, P50 CA089393-060012, P50 CA089393-070012, P50 CA089393-080012]; NHGRI NIH HHS [R01 HG004069, 1R01 HG004069-02, R01 HG004069-02]; NIDDK NIH HHS [R01 DK074967, R01 DK074967-01A1, R01DK074967, R56 DK074967, R56 DK074967-01] NR 53 TC 498 Z9 511 U1 3 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 2008 VL 132 IS 6 BP 958 EP 970 DI 10.1016/j.cell.2008.01.018 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 278GR UT WOS:000254273600015 PM 18358809 ER PT J AU Tullet, JMA Hertweck, M An, JH Baker, J Hwang, JY Liu, S Oliveira, RP Baumeister, R Blackwell, TK AF Tullet, Jennifer M. A. Hertweck, Maren An, Jae Hyung Baker, Joseph Hwang, Ji Yun Liu, Shu Oliveira, Riva P. Baumeister, Ralf Blackwell, T. Keith TI Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans SO CELL LA English DT Article ID RESTRICTION-INDUCED LONGEVITY; OXIDATIVE STRESS-RESPONSE; EXTENDS LIFE-SPAN; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; DAF-16; GENE; RESISTANCE; PROTEINS; MUTATION AB Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS. C1 [Tullet, Jennifer M. A.; An, Jae Hyung; Baker, Joseph; Oliveira, Riva P.; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst,Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. [Hertweck, Maren; Liu, Shu; Baumeister, Ralf] Univ Freiburg, ZBMZ, Ctr Biochem & Mol Cell Res, Fac Med,Bioinformat & Mol Genet Fac Biol, D-79104 Freiburg, Germany. [An, Jae Hyung; Hwang, Ji Yun] Yonsei Univ, Prot Network Res Ctr, Seoul 120749, South Korea. [Baumeister, Ralf] Univ Freiburg, Ctr Syst Biol ZBSA, D-79104 Freiburg, Germany. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst,Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu RI Tullet, Jennifer/C-1779-2008; Oliveira, Riva/J-8408-2013; OI Oliveira, Riva/0000-0002-4917-7646; Tullet, Jennifer/0000-0002-2037-526X FU NIDDK NIH HHS [T32 DK07260]; NIGMS NIH HHS [R01 GM062891-06, 2 R01 GM062891, 5 F32 GM070088-02, R01 GM062891, R01 GM062891-05, R01 GM062891-07, R01 GM062891-08] NR 42 TC 337 Z9 364 U1 6 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 2008 VL 132 IS 6 BP 1025 EP 1038 DI 10.1016/j.cell.2008.01.030 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 278GR UT WOS:000254273600020 PM 18358814 ER PT J AU Kim, JW Chu, JL Shen, XH Wang, JL Orkin, SH AF Kim, Jonghwan Chu, Jianlin Shen, Xiaohua Wang, Jianlong Orkin, Stuart H. TI An extended transcriptional network for pluripotency of embryonic stem cells SO CELL LA English DT Article ID DEVELOPMENTAL REGULATORS; MAMMALIAN-CELLS; SOMATIC-CELLS; MOUSE EMBRYOS; SELF-RENEWAL; ES CELLS; C-MYC; PROTEIN; GENOME; NANOG AB Much attention has focused on a small set of transcription factors that maintain human or mouse embryonic stem (ES) cells in a pluripotent state. To gain a more complete understanding of the regulatory network that maintains this state, we identified target promoters of nine transcription factors, including somatic cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) and others (Nanog, Dax1, Rex1, Zpf281, and Nac1), on a global scale in mouse ES cells. We found that target genes fall into two classes: promoters bound by few factors tend to be inactive or repressed, whereas promoters bound by more than four factors are largely active in the pluripotent state and become repressed upon differentiation. Furthermore, we propose a transcriptional hierarchy for reprogramming factors and broadly distinguish targets of c-Myc versus other factors. Our data provide a resource for exploration of the complex network maintaining pluripotency. C1 [Kim, Jonghwan; Chu, Jianlin; Shen, Xiaohua; Wang, Jianlong; Orkin, Stuart H.] Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kim, Jonghwan; Chu, Jianlin; Shen, Xiaohua; Wang, Jianlong; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Jonghwan; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dept Pediat Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU Howard Hughes Medical Institute NR 59 TC 784 Z9 801 U1 5 U2 56 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 2008 VL 132 IS 6 BP 1049 EP 1061 DI 10.1016/j.cell.2008.02.039 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 278GR UT WOS:000254273600022 PM 18358816 ER PT J AU Zhu, ED Demay, MB Gori, F AF Zhu, Eric D. Demay, Marie B. Gori, Francesca TI Wdr5 is essential for osteoblast differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN; CHONDROCYTE DIFFERENTIATION; H3K4 METHYLATION; BONE-DEVELOPMENT; GENE-EXPRESSION; WNT; PROTEIN; LRP5; APOPTOSIS; CELLS AB Wdr5 is developmentally expressed in osteoblasts and accelerates osteoblast differentiation in vitro and in vivo. To address whether Wdr5 is essential for osteoblast differentiation, plasmid-based small interfering RNAs were used to stably suppress endogenous Wdr5 protein levels in MC3T3-E1 cells. Reduction of endogenous Wdr5 levels markedly inhibited osteoblast differentiation, evidenced by a significant decrease in alkaline phosphatase activity, Runx-2 and osteocalcin mRNAs, and absence of mineralized matrix formation. Wdr5 suppression also resulted in a reduction of histone H3 lysine 4 trimethylation, confirming its critical role in this modification. Because Wdr5 overexpression enhances canonical Wnt signaling in osteoblasts in vivo, the effects of Wdr5 silencing on this pathway were examined. The expression of the canonical Wnt target gene, c-myc, was decreased, whereas that of sfrp2, which is repressed by Wnt signaling, was increased with Wdr5 knockdown. Although only a minimal increase in apoptosis was observed, the antiapoptotic effect of Wnt signaling was also impaired with Wdr5 silencing. The expression of canonical Wnts was significantly decreased with Wdr5 knockdown, resulting in a decrease in nuclear beta-catenin protein levels. Activation of the canonical Wnt signaling pathway did not overcome the effects of Wdr5 knockdown on the expression of Wnt target genes. Chromatin immunoprecipitation demonstrated that Wdr5 is present on the Wnt1 promoter and on canonical Wnt response elements of the c-myc and Runx-2 promoters. These studies demonstrate that Wdr5 suppression interferes with the canonical Wnt signaling pathway at multiple stages and that optimal Wdr5 levels are required for induction of the osteoblast phenotype. C1 [Zhu, Eric D.; Demay, Marie B.; Gori, Francesca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Gori, F (reprint author), 50 Blossom St, Boston, MA 02114 USA. EM gori@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK36597] NR 36 TC 29 Z9 30 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 MAR 21 PY 2008 VL 283 IS 12 BP 7361 EP 7367 DI 10.1074/jbc.M703304200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 274JP UT WOS:000253997900010 PM 18201971 ER PT J AU Zhang, H Li, ZH Zhang, MQ Katz, MS Zhang, BX AF Zhang, Hua Li, Zhen-Hua Zhang, Michael Q. Katz, Michael S. Zhang, Bin-Xian TI Heat shock protein 90 beta 1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYPE-2 DIABETIC-PATIENTS; ENDOPLASMIC-RETICULUM; SUBSTRATE OXIDATION; INTRACELLULAR CA2+; CALCIUM-TRANSPORT; SKELETAL-MUSCLE; CELLS; HSP90; DYSFUNCTION; GLUCOSE AB Nonesterified fatty acids may influence mitochondrial function by alterations in gene expression, metabolism, and/or mitochondrial Ca2+ ([Ca2+](m)) homeostasis. We have previously reported that polyunsaturated fatty acids induce Ca2+ efflux from mitochondria, an action that may deplete [Ca2+](m) and thus contribute to nonesterified fatty acid-responsive mitochondrial dysfunction. Here we show that the chaperone protein heat shock protein 90 beta 1 (hsp90 beta 1) is required for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux (PIMCE). Retinoic acid induced differentiation of human teratocarcinoma NT2 cells in association with attenuation of PIMCE. Proteomic analysis of mitochondrial proteins revealed that hsp90 beta 1, among other proteins, was reduced in retinoic acid-differentiated cells. Blockade of PIMCE in NT2 cells by 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin, a known inhibitor of the chaperone activity of hsp90, and hsp90 beta 1 RNA interference demonstrated that hsp90 beta 1 is essential for PIMCE. We also show localization of hsp90 beta 1 in mitochondria by Western blot and immunofluorescence. Distinctive effects of inhibitors binding to the N or C terminus of hsp90 on PIMCE in isolated mitochondria suggested that the C terminus of hsp90 beta 1 plays a critical role in PIMCE. C1 [Zhang, Hua; Li, Zhen-Hua; Zhang, Michael Q.; Katz, Michael S.; Zhang, Bin-Xian] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Audie L Murphy Div, S Texas Vet Hlth Care Syst,Geriatr Res Educ & Cli, San Antonio, TX 78229 USA. RP Zhang, BX (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Audie L Murphy Div, S Texas Vet Hlth Care Syst,Geriatr Res Educ & Cli, GRECC 182,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL075011] NR 40 TC 8 Z9 8 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 MAR 21 PY 2008 VL 283 IS 12 BP 7580 EP 7589 DI 10.1074/jbc.M707192200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 274JP UT WOS:000253997900033 PM 18178560 ER PT J AU Safai, S Bortfeld, T Engelsman, M AF Safai, Sairos Bortfeld, Thomas Engelsman, Martijn TI Comparison between the lateral penumbra of a collimated double-scattered beam and uncollimated scanning beam in proton radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MULTIPLE COULOMB SCATTERING; PENCIL BEAMS; INHOMOGENEITIES; DOSIMETRY; ENERGY; MODEL AB Intensity modulated proton radiotherapy ( IMPT) can reduce the dose to critical structures by optimizing the distribution and intensity of individual pencil beams. The IMPT can be delivered by dynamically scanning a pencil beam with variable intensity and energy across the tumor target volume. The lateral penumbra of an uncollimated pencil beam is compromised, however, by the scattering in air between the vacuum window and the patient, and by the initial beam size. In this study, we compare the transversal penumbra of a pencil beam to the one of a collimated Gaussian broad divergent beam, such as the one produced by the double scattering system, for different range compensator thicknesses, collimator-to-surface distances ( CSD), proton range and pencil beam sizes ( sigma(0)). The effect of vacuum and helium in the nozzle on the pencil beam lateral profile further downstream is also investigated. The lateral spatial intensity distribution for the collimated Gaussian broad divergent proton beam is modeled using the generalized Fermi-Eyges theory. The model is validated with measurements of the lateral profile in water at different depths for two different ranges ( 7.7 cm and 22.1 cm, respectively). Nearly 2500 treatment fields are analyzed to establish typical clinical beam configurations, such as the range compensator thicknesses, CSD and range, which we use to predict the 80%-20% lateral penumbra. The penumbra of the collimated broad divergent beam is calculated for fixed source-to-surface distance ( SSD) of 220 cm and source size of 2.5 cm ( sigma). The results show that the model predicts the penumbra at different water depths with accuracy better than 0.2 mm. At depths larger than 7.6 cm ( minimum range of the clinical fields analyzed), the accuracy is better than 3%. The treatment fields feature the following average configuration: the range compensator thickness of 6.5 +/- 2.8 cm( max 19.4 cm), CSD 11.9 +/- 3.8 cm ( max 29.4 cm) and range of 16.0 +/- 6.1 cm. The penumbra of a pencil beam at shallow depth is in general larger ( i.e., worse) than the penumbra of a collimated beam, but better at larger depths. The depth at which the two penumbras are identical exhibits only a small dependence on the proton range, but is strongly affected by the collimator-to-surface distance. For CSD 10 cm, range compensator thickness 6 cm, SSD 220 cm and source size 2.5 cm, this depth is 11.5 cm for a 5 mm pencil beam, and 9.1 cm for a 3 mm pencil beam. For most of the clinical sites considered, assuming the beam configurations of this study, the pencil beam penumbra is larger ( i.e., worse). By moving the vacuum window downstream or by replacing air with helium in the gantry nozzle, the dosimetrical benefit of scanning would be drastically improved, especially for small sigma(0) ( 5 mm or less). C1 [Safai, Sairos; Bortfeld, Thomas; Engelsman, Martijn] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02474 USA. RP Safai, S (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02474 USA. EM sairos.safai@psi.ch NR 29 TC 32 Z9 32 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2008 VL 53 IS 6 BP 1729 EP 1750 DI 10.1088/0031-9155/53/6/016 PG 22 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 276WZ UT WOS:000254175700016 PM 18367800 ER PT J AU Zeng, Q Wang, SX Lim, GW Yang, LL Mao, J Sung, BI Chang, Y Lim, JA Guo, GS Mao, JR AF Zeng, Qing Wang, Shuxing Lim, Grewo Yang, Liling Mao, Ji Sung, Backil Chang, Yang Lim, Jeong-Ae Guo, Gongshe Mao, Jianren TI Exacerbated mechanical allodynia in rats with depression-like behavior SO BRAIN RESEARCH LA English DT Review DE allodynia; melatonin; depression; anterior cingular cortex; neuropathic pain; nerve injury; WKY rat ID ANTERIOR CINGULATE CORTEX; LOW-BACK-PAIN; CHRONIC MUSCULOSKELETAL PAIN; PITUITARY-ADRENAL AXIS; TAIL SUSPENSION TEST; TRKB MESSENGER-RNA; MELATONIN RECEPTORS; DIABETIC-NEUROPATHY; CLUSTER HEADACHE; ANIMAL-MODEL AB Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report that both mechanical allodynia and depression-like behavior were significantly exacerbated after peripheral nerve injury in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats with demonstrable depression-like behavior. Administration of melatonin into the anterior cingular cortex contralateral to peripheral nerve injury prevented the exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in WKY rats. Moreover, there was a lower plasma melatonin concentration and a lower melatonin receptor expression in the anterior cingular cortex in WKY rats than in Wistar rats. These results suggest that there exists a reciprocal relationship between mechanical allodynia and depression-like behavior and the melatoninergic system in the anterior cingular cortex might play an important role in the interaction between pain and depression. (c) 2008 Elsevier B.V. All rights reserved. C1 [Zeng, Qing; Wang, Shuxing; Lim, Grewo; Yang, Liling; Mao, Ji; Sung, Backil; Chang, Yang; Lim, Jeong-Ae; Guo, Gongshe; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Transplant Pain Res,Dept Anesthesia & Cri, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Transplant Pain Res,Dept Anesthesia & Cri, WACC 324,15 Parlman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDCR NIH HHS [R01 DE018538, R01 DE018538-01, R01 DE18538]; NINDS NIH HHS [R01 NS042661, R01 NS045681, R01 NS045681-04, R01 NS45681, R01 NS042661-04] NR 101 TC 43 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 20 PY 2008 VL 1200 BP 27 EP 38 DI 10.1016/j.brainres.2008.01.038 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 290BJ UT WOS:000255097400004 PM 18289511 ER PT J AU Bonner-Weir, S AF Bonner-Weir, Susan TI Islet neogenesis SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Meeting Abstract C1 [Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Boston, MA USA. OI Bonner-Weir, Susan/0000-0003-4682-0656 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 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD MAR 20 PY 2008 VL 79 SU 1 BP S3 EP S4 DI 10.1016/S0168-8227(08)70651-X PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 350OQ UT WOS:000259362500008 ER PT J AU Kahn, S AF Kahn, Steven TI beta-cell function and volume in the development of Type 2 diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Meeting Abstract C1 [Kahn, Steven] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 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 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD MAR 20 PY 2008 VL 79 SU 1 BP S9 EP S9 DI 10.1016/S0168-8227(08)70667-3 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 350OQ UT WOS:000259362500024 ER PT J AU Schnitt, SJ Harris, JR AF Schnitt, Stuart J. Harris, Jay R. TI Evolution of breast-conserving therapy for localized breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PRIMARY RADIATION-THERAPY; RECURRENCE; TAMOXIFEN; EXCISION; WOMEN C1 [Schnitt, Stuart J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Harris, Jay R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Schnitt, SJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. NR 8 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2008 VL 26 IS 9 BP 1395 EP 1396 DI 10.1200/JCO.2007.14.1432 PG 2 WC Oncology SC Oncology GA 276YC UT WOS:000254178600001 PM 18349387 ER PT J AU Viale, G Regan, MM Maiorano, E Mastropasqua, MG Golouh, R Perin, T Brown, RW Kovacs, A Pillay, K Ohlschlegel, C Braye, S Grigolato, P Rusca, T Gelber, RD Castiglione-Gertsch, M Price, KN Goldhirsch, A Gusterson, BA Coates, AS AF Viale, Giuseppe Regan, Meredith M. Maiorano, Eugenio Mastropasqua, Mauro G. Golouh, Rastko Perin, Tiziana Brown, Robert W. Kovacs, Aniko Pillay, Komala Ohlschlegel, Christian Braye, Stephen Grigolato, Piergiovanni Rusca, Tiziana Gelber, Richard D. Castiglione-Gertsch, Monica Price, Karen N. Goldhirsch, Aron Gusterson, Barry A. Coates, Alan S. TI Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: Predictive value of centrally reviewed expression of estrogen and progesterone receptors - International Breast Cancer Study Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TX ID RANDOMIZED-TRIALS; CLINICAL-TRIALS; CHEMOTHERAPY; SUBSETS AB Purpose To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer. Patients and Methods International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology. Results Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX. Conclusion Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER. C1 Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. Univ Bari, Dept Pathol Anat, Bari, Italy. Ctr Riferimento Oncol, Div Pathol, I-33081 Aviano, Italy. Univ Brescia, Brescia, Italy. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp,Stat Ctr, Boston, MA 02115 USA. Inst Oncol, Ljubljana, Slovenia. Melbourne Pathol, Collingwood, Vic, Australia. Univ Newcastle & Anat Pathol, Australian New Zealand Breast Canc Trials Grp, Hunter Area Pathol Serv, John Hunter Hosp, New Lambton Hts, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Goteborg Sahlgrenska Univ Hosp, Dept Pathol, Gothenburg, Sweden. Univ Cape Town, Div Anat Pathol, Dept Clin Lab Serv, Natl Hlth Lab Serv, ZA-7925 Cape Town, South Africa. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Kantonsspital, St Gallen, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Ist Cantonale Patol, Locarno, Switzerland. Oncol Inst So Switzerland, Bellaterra, Spain. Swiss Grp Clin Canc Res, Bellaterra, Spain. Univ Glasgow, Fac Med, Div Canc Sci & Mol Pathol, Glasgow G12 8QQ, Lanark, Scotland. RP Viale, G (reprint author), Ist Europeo Oncol, Div Anat Patol, Via Ripamonti 435, I-20141 Milan, Italy. EM giuseppe.viale@ieo.it RI gusterson, barry/D-3752-2009; Maiorano, Eugenio/F-1382-2015 FU NCI NIH HHS [CA-75362] NR 22 TC 66 Z9 67 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2008 VL 26 IS 9 BP 1404 EP 1410 DI 10.1200/JCO.2007.10.6393 PG 7 WC Oncology SC Oncology GA 276YC UT WOS:000254178600005 PM 18349391 ER PT J AU Janne, PA Simon, GR Langer, CJ Taub, RN Dowlati, A Fidias, P Monberg, M Obasaju, C Kindler, H AF Janne, Pasi A. Simon, George R. Langer, Corey J. Taub, Robert N. Dowlati, Afshin Fidias, Panos Monberg, Matthew Obasaju, Coleman Kindler, Hedy TI Phase II trial of pemetrexed and gemcitabine in chemotherapy-naive malignant pleural mesothelioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID FRONT-LINE THERAPY; CELL LUNG-CANCER; LEUKEMIA GROUP-B; EUROPEAN-ORGANIZATION; PROGNOSTIC-FACTORS; TOXICITY CRITERIA; CISPLATIN; COMBINATION; EPIDEMIC; SURVIVAL AB Purpose Pemetrexed and gemcitabine have single-agent activity in malignant pleural mesothelioma (MPM). The combination of pemetrexed/gemcitabine has not previously been studied in MPM to our knowledge. Patients and Methods Patients with histologic or cytologic diagnosis of MPM were included. Cohort 1 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 8, and cohort 2 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 1. Cycles were repeated every 21 days; all patients were supplemented with folic acid and vitamin B-12 and received dexamethasone. Results One hundred eight patients (cohort 1, n = 56; cohort 2, n = 52) with pleural mesothelioma were enrolled. Among assessable patients, response rate was 26.0% in cohort 1 and 17.1% in cohort 2. Median time to disease progression was 4.34 months for cohort 1 and 7.43 months for cohort 2. Median survival was 8.08 months for cohort 1 (1-year survival = 31.14%) and 10.12 months for cohort 2 (1-year survival = 45.80%). In cohorts 1 and 2, incidence of grade 4 neutropenia was 25.0% and 29.4%, grade 4 thrombocytopenia was 14.3% and 3.9%, grade 3 or 4 anemia was 5.4% and 5.9%, and grade 3 or 4 fatigue was 23.2% and 15.7%, respectively. Conclusion The combination of pemetrexed and gemcitabine resulted in moderate clinical activity in MPM. However, the median survival times are similar to those with single-agent pemetrexed and inferior to outcomes observed with cisplatin in combination with an antifolate. C1 [Janne, Pasi A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Columbia Univ, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Janne, PA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Lowe Ctr Thorac Oncol, 44 Binney St,Dana D820A, Boston, MA 02115 USA. EM pjanne@partners.org NR 39 TC 21 Z9 21 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 MAR 20 PY 2008 VL 26 IS 9 BP 1465 EP 1471 DI 10.1200/JCO.2007.14.7611 PG 7 WC Oncology SC Oncology GA 276YC UT WOS:000254178600013 PM 18349397 ER PT J AU Kathiresan, S Melander, O Anevski, D Guiducci, C Burtt, NP Roos, C Hirschhorn, JN Berglund, G Hedblad, B Groop, L Altshuler, DM Newton-Cheh, C Orho-Melander, M AF Kathiresan, Sekar Melander, Olle Anevski, Dragi Guiducci, Candace Burtt, Noel P. Roos, Charlotta Hirschhorn, Joel N. Berglund, Goran Hedblad, Bo Groop, Leif Altshuler, David M. Newton-Cheh, Christopher Orho-Melander, Marju TI Polymorphisms associated with cholesterol and risk of cardiovascular events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; GENERAL-POPULATION; ARTERY-DISEASE; TRIGLYCERIDES; LOCI; CONTRIBUTES; GENOME; CURVE; MALMO AB Background: Common single-nucleotide polymorphisms (SNPs) that are associated with blood low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol modestly affect lipid levels. We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease. Methods: We studied SNPs at nine loci in 5414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study. We first validated the association between SNPs and either LDL or HDL cholesterol and subsequently created a genotype score on the basis of the number of unfavorable alleles. We used Cox proportional-hazards models to determine the time to the first cardiovascular event in relation to the genotype score. Results: All nine SNPs showed replication of an association with levels of either LDL or HDL cholesterol. With increasing genotype scores, the level of LDL cholesterol increased from 152 mg to 171 mg per deciliter (3.9 to 4.4 mmol per liter), whereas HDL cholesterol decreased from 60 mg to 51 mg per deciliter (1.6 to 1.3 mmol per liter). During follow-up (median, 10.6 years), 238 subjects had a first cardiovascular event. The genotype score was associated with incident cardiovascular disease in models adjusted for covariates including baseline lipid levels (P<0.001). The use of the genotype score did not improve the clinical risk prediction, as assessed by the C statistic. However, there was a significant improvement in risk classification with the use of models that included the genotype score, as compared with those that did not include the genotype score. Conclusions: A genotype score of nine validated SNPs that are associated with modulation in levels of LDL or HDL cholesterol was an independent risk factor for incident cardiovascular disease. The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors. C1 [Kathiresan, Sekar; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Div Cardiol, Boston, MA 02114 USA. [Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kathiresan, Sekar; Altshuler, David M.; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hirschhorn, Joel N.; Altshuler, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol & Genet, Boston, MA 02115 USA. [Kathiresan, Sekar; Guiducci, Candace; Burtt, Noel P.; Hirschhorn, Joel N.; Altshuler, David M.; Newton-Cheh, Christopher] MIT, Broad Inst, Cambridge, MA 02139 USA. [Kathiresan, Sekar; Guiducci, Candace; Burtt, Noel P.; Hirschhorn, Joel N.; Altshuler, David M.; Newton-Cheh, Christopher] Harvard Univ, Cambridge, MA 02138 USA. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden. [Anevski, Dragi; Roos, Charlotta; Groop, Leif; Orho-Melander, Marju] Lund Univ, Malmo Univ Hosp, Dept Endocrinol & Diabet, Malmo, Sweden. [Berglund, Goran] Lund Univ, Malmo Univ Hosp, Dept Internal Med, Malmo, Sweden. [Hedblad, Bo] Lund Univ, Malmo Univ Hosp, Dept Epidemiol Res, Malmo, Sweden. [Anevski, Dragi] Chalmers, S-41296 Gothenburg, Sweden. [Groop, Leif] Helsinki Univ Hosp, Helsinki, Finland. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Div Cardiol, 25 New Chardon St,Suite 301, Boston, MA 02114 USA. EM skathiresan@partners.org RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NHLBI NIH HHS [K23-HL080025, K23-HL083102] NR 36 TC 402 Z9 405 U1 0 U2 16 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 MAR 20 PY 2008 VL 358 IS 12 BP 1240 EP 1249 DI 10.1056/NEJMoa0706728 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 275TL UT WOS:000254094400005 PM 18354102 ER PT J AU Dodson, TB Raje, NS Caruso, PA Rosenberg, AE Smullin, SE Harris, NL AF Dodson, Thomas B. Raje, Noopur S. Caruso, Paul A. Rosenberg, Andrew E. Smullin, Steven E. Harris, Nancy Lee TI A woman with a nonhealing ulcer of the jaw - Gingival ulceration, inflammation, and acute osteomyelitis with actinomyces, all associated with necrosis of bone (bisphosphonate-related osteonecrosis of bone) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MULTIPLE-MYELOMA; ZOLEDRONIC ACID; RISK-FACTORS; AMERICAN-SOCIETY; SKELETAL COMPLICATIONS; BREAST-CARCINOMA; DOUBLE-BLIND; PHOSSY-JAW; METASTASES; CANCER C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. [Raje, Noopur S.] Harvard Univ, Sch Med, Dept Oncol, Cambridge, MA 02138 USA. [Caruso, Paul A.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Rosenberg, Andrew E.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 42 TC 28 Z9 29 U1 0 U2 2 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 MAR 20 PY 2008 VL 358 IS 12 BP 1283 EP 1291 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 275TL UT WOS:000254094400011 PM 18354107 ER PT J AU Goetz, MB Bowman, C Hoang, T Anaya, H Osborn, T Gifford, AL Asch, SM AF Goetz, Matthew B. Bowman, Candice Hoang, Tuyen Anaya, Henry Osborn, Teresa Gifford, Allen L. Asch, Steven M. TI Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID PREVENTIVE SERVICES; CLINICAL REMINDERS; COST-EFFECTIVENESS; CHRONIC ILLNESS; UNITED-STATES; PRIMARY-CARE; OF-CARE; INFECTION; BARRIERS; LESSONS AB Background: We describe how we used the framework of the U. S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis-a point of substantial importance to the VA, which is the largest provider of HIV care in the United States. Methods: Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA. Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation. Results: Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3-5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations. Discussion: This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4). C1 [Goetz, Matthew B.] VA Greater Angeles Healthcare Syst, Infect Dis Sect 111F, Los Angeles, CA USA. [Bowman, Candice] VA San Diego Healthcare Syst, San Diego, CA USA. [Osborn, Teresa] Vet Integrate Serv Network 22, Long Beach, CA USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Adm Hosp, VA Bedford Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Hoang, Tuyen; Anaya, Henry; Asch, Steven M.] VA Greater Angeles Healthcare Syst, Gen Med 111G, Los Angeles, CA USA. RP Goetz, MB (reprint author), VA Greater Angeles Healthcare Syst, Infect Dis Sect 111F, Los Angeles, CA USA. EM Matthew.Goetz@va.gov; candybowman@gmail.com; Tuyen.Hoang@va.gov; Henry.Anaya@va.gov; Teresa.Osborn@va.gov; Allen.Gifford@va.gov; Steven.Asch@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU U. S. Department of Veterans Affairs, Health Services Research and Development Service [06-001] FX We acknowledge the contributions of Robert M. Smith, MD for his invaluable contributions to the development and implementation of the HIV testing clinical reminder. This work was supported by the U. S. Department of Veterans Affairs, Health Services Research and Development Service (Service Directed Project 06-001). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 47 TC 18 Z9 18 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAR 19 PY 2008 VL 3 AR 16 DI 10.1186/1748-5908-3-16 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QT UT WOS:000265149900001 PM 18353185 ER PT J AU Krein, SL Bernstein, SJ Fletcher, CE Makki, F Goldzweig, CL Watts, B Vijan, S Hayward, RA AF Krein, Sarah L. Bernstein, Steven J. Fletcher, Carol E. Makki, Fatima Goldzweig, Caroline L. Watts, Brook Vijan, Sandeep Hayward, Rodney A. TI Improving eye care for veterans with diabetes: An example of using the QUERI steps to move from evidence to implementation: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID RESEARCH INITIATIVE QUERI; SELF-MANAGEMENT; MELLITUS; RETINOPATHY; SERVICES; PHOTOCOAGULATION; INTERVENTIONS; COMPLICATIONS; PROGRESSION; OUTPATIENT AB Background: Despite being a critical part of improving healthcare quality, little is known about how best to move important research findings into clinical practice. To address this issue, the Department of Veterans Affairs (VA) developed the Quality Enhancement Research Initiative (QUERI), which provides a framework, a supportive structure, and resources to promote the more rapid implementation of evidence into practice. Methods: This paper uses a practical example to demonstrate the use of the six-step QUERI process, which was developed as part of QUERI and provides a systematic approach for moving along the research to practice pipeline. Specifically, we describe a series of projects using the six-step framework to illustrate how this process guided work by the Diabetes Mellitus QUERI (DM-QUERI) Center to assess and improve eye care for veterans with diabetes. Results: Within a relatively short time, DM-QUERI identified a high-priority issue, developed evidence to support a change in the diabetes eye screening performance measure, and identified a gap in quality of care. A prototype scheduling system to address gaps in screening and follow-up also was tested as part of an implementation project. We did not succeed in developing a fully functional pro-active scheduling system. This work did, however, provide important information to help us further understand patients' risk status, gaps in follow-up at participating eye clinics, specific considerations for additional implementation work in the area of proactive scheduling, and contributed to a change in the prevailing diabetes eye care performance measure. Conclusion: Work by DM-QUERI to promote changes in the delivery of eye care services for veterans with diabetes demonstrates the value of the QUERI process in facilitating the more rapid implementation of evidence into practice. However, our experience with using the QUERI process also highlights certain challenges, including those related to the hybrid nature of the research-operations partnership as a mechanism for promoting rapid, system-wide implementation of important research findings. In addition, this paper suggests a number of important considerations for future implementation work, both in the area of pro-active scheduling interventions, as well as for implementation science in general. C1 [Krein, Sarah L.; Bernstein, Steven J.; Vijan, Sandeep; Hayward, Rodney A.] VA Ann Arbor Healthcare Syst, Hlth Serv Res & Dev, Ann Arbor, MI USA. [Krein, Sarah L.; Bernstein, Steven J.; Fletcher, Carol E.; Makki, Fatima; Vijan, Sandeep; Hayward, Rodney A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Goldzweig, Caroline L.] VA Greater Angeles Healthcare Syst, Gen Internal Med & Clin Informat, Los Angeles, CA USA. [Watts, Brook] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. RP Krein, SL (reprint author), VA Ann Arbor Healthcare Syst, Hlth Serv Res & Dev, Ann Arbor, MI USA. EM sarah.krein@va.gov; sbernste@umich.edu; carol.fletcher@va.gov; fatima.makki@va.gov; caroline.goldzweig@va.gov; brook.watts@va.gov; svijan@umich.edu; rhayward@umich.edu RI Krein, Sarah/E-2742-2014 OI Krein, Sarah/0000-0003-2111-8131 FU U. S. Department of Veterans Affairs, Health Services Research and Development Service [DIB 98-001, DIT 02-064]; NIDDK of the National Institutes of Health [P60DK-20572] FX This study was supported through grant funding from the U. S. Department of Veterans Affairs, Health Services Research and Development Service: DIB 98-001 and DIT 02-064. This work also was supported, in part, by the Michigan Diabetes Research and Training Center Grant P60DK-20572 from the NIDDK of the National Institutes of Health. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. The authors wish to thank Matt Shevrin for assisting with data management throughout the project and, as needed, for this article. NR 39 TC 10 Z9 10 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAR 19 PY 2008 VL 3 AR 18 DI 10.1186/1748-5908-3-18 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QT UT WOS:000265149900003 PM 18353187 ER PT J AU Masciari, S Van den Abbeele, AD Diller, LR Rastarhuyeva, I Yap, J Schneider, K Digianni, L Li, FP Fraumeni, JF Syngal, S Garber, JE AF Masciari, Serena Van den Abbeele, Annick D. Diller, Lisa R. Rastarhuyeva, Iryna Yap, Jeffrey Schneider, Katherine Digianni, Lisa Li, Frederick P. Fraumeni, Joseph F., Jr. Syngal, Sapna Garber, Judy E. TI F18-fluorodeoxyglucose-positron emission tomography/computed tomography screening in Li-Fraumeni syndrome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SOFT-TISSUE SARCOMA; P53 MUTATIONS; F-18 FLUORODEOXYGLUCOSE; FDG-PET; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; COLORECTAL-CANCER; FAMILIAL SYNDROME; RATIONAL APPROACH; DOSE REDUCTION AB Context Individuals with Li-Fraumeni syndrome ( LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds. Objective To gather preliminary data with which to evaluate F18- fluorodeoxyglucose positron emission tomography/ computed tomography ( FDG- PET/ CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds. Design, Setting, and Participants Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill- health were offered FDG-PET/ CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist. Main OutcomeMeasure The primary outcome was the detection of new primary cancers using FDG- PET/ CT scanning. Results Of 15 individuals, baseline FDG- PET/ CT scan identified asymptomatic cancers in 3 ( 20%). Two individuals had papillary thyroid cancers ( stage II and stage III) and one individual had stage II esophageal adenocarcinoma. Conclusions These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration. C1 [Masciari, Serena; Schneider, Katherine; Digianni, Lisa; Li, Frederick P.; Syngal, Sapna; Garber, Judy E.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Van den Abbeele, Annick D.; Rastarhuyeva, Iryna; Yap, Jeffrey] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Diller, Lisa R.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Fraumeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,SM 209, Boston, MA 02115 USA. EM judy_garber@dfci.harvard.edu NR 35 TC 49 Z9 51 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 19 PY 2008 VL 299 IS 11 BP 1315 EP 1319 DI 10.1001/jama.299.11.1315 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 275NO UT WOS:000254079100022 PM 18349092 ER PT J AU Scheuner, MT Sieverding, P Shekelle, PG AF Scheuner, Maren T. Sieverding, Pauline Shekelle, Paul G. TI Delivery of genomic medicine for common chronic adult diseases - A systematic review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PHYSICIANS; FAMILIAL CANCER-RISK; BREAST-CANCER; GENETIC DISCRIMINATION; COLORECTAL-CANCER; PSYCHOLOGICAL OUTCOMES; INFORMATION NEEDS; HEALTH INSURERS; UNITED-STATES AB Context The greatest public health benefit of advances in understanding the human genome may be realized for common chronic diseases such as cardiovascular disease, diabetes mellitus, and cancer. Attempts to integrate such knowledge into clinical practice are still in the early stages, and as a result, many questions surround the current state of this translation. Objective To synthesize current information on genetic health services for common adult- onset conditions by examining studies that have addressed the outcomes, consumer information needs, delivery, and challenges in integrating these services. Data Sources MEDLINE articles published between January 2000 and February 2008. Study Selection Original research articles and systematic reviews dealing with common chronic adult- onset conditions were reviewed. A total of 3371 citations were reviewed, 170 articles retrieved, and 68 articles included in the analysis. Data Extraction Data were independently extracted by one reviewer and checked by another with disagreement resolved by consensus. Variables assessed included study design and 4 key areas: outcomes of genomic medicine, consumer information needs, delivery of genomic medicine, and challenges and barriers to integration of genomic medicine. Data Synthesis Sixty- eight articles contributed data to the synthesis: 5 systematic reviews, 8 experimental studies, 35 surveys, 7 pre/ post studies, 3 observational studies, and 10 qualitative reports. Three systematic reviews, 4 experimental studies, and 9 additional studies reported on outcomes of genetic services. Generally there were modest positive effects on psychological outcomes such as worry and anxiety, behavioral outcomes have shown mixed results, and clinical outcomes were less well studied. One systematic review, 1 randomized controlled trial, and 14 other studies assessed consumer information needs and found in general that genetics knowledge was reported to be low but that attitudes were generally positive. Three randomized controlled trials and 13 other studies assessed how genomic medicine is delivered and newer models of delivery. One systematic review and 19 other studies assessed barriers; the most consistent finding was the self- assessed inadequacy of the primary care work-force to deliver genetic services. Additional identified barriers included lack of oversight of genetic testing and concerns about privacy and discrimination. Conclusion Many gaps in knowledge about organization, clinician, and patient needs must be filled to translate basic and clinical science advances in genomics of common chronic diseases into practice. C1 [Scheuner, Maren T.; Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90401 USA. [Sieverding, Pauline] Dept Vet Affairs, Hlth Serv Res & Dev Serv, Washington, DC USA. [Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Scheuner, MT (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM scheuner@rand.org NR 67 TC 170 Z9 172 U1 5 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 19 PY 2008 VL 299 IS 11 BP 1320 EP 1334 DI 10.1001/jama.299.11.1320 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 275NO UT WOS:000254079100023 PM 18349093 ER PT J AU Schrag, D AF Schrag, Deborah TI Enhancing cancer registry data to promote rational health system design SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID OVARIAN-CANCER; SPECIALTY; SURVIVAL; OUTCOMES C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM deborah-schrag@dfci.harvard.edu NR 6 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 19 PY 2008 VL 100 IS 6 BP 378 EP 379 DI 10.1093/jnci/djn060 PG 2 WC Oncology SC Oncology GA 278OT UT WOS:000254296900002 PM 18334703 ER PT J AU Rollins, SM Peppercorn, A Young, JS Drysdale, M Baresch, A Bikowski, MV Ashford, DA Quinn, CP Handfield, M Hillman, JD Lyons, CR Koehler, TM Calderwood, SB Ryan, ET AF Rollins, Sean M. Peppercorn, Amanda Young, John S. Drysdale, Melissa Baresch, Andrea Bikowski, Margaret V. Ashford, David A. Quinn, Conrad P. Handfield, Martin Hillman, Jeffrey D. Lyons, C. Rick Koehler, Theresa M. Calderwood, Stephen B. Ryan, Edward T. TI Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis SO PLOS ONE LA English DT Article AB In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets. C1 [Rollins, Sean M.; Peppercorn, Amanda; Young, John S.; Baresch, Andrea; Bikowski, Margaret V.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drysdale, Melissa; Lyons, C. Rick] Univ New Mexico Hlth Sci Ctr, Albuquerque, NM USA. [Drysdale, Melissa; Koehler, Theresa M.] Univ Texas Med Sch Houston, Dept Microbiol & Mol Genet, Houston, TX USA. [Ashford, David A.] USDA, APHIS, Sao Paulo, Brazil. [Quinn, Conrad P.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Handfield, Martin] Univ Florida, Coll Dentist, Ctr Mol Microbiol, Dept Oral Biol, Gainesville, FL USA. [Hillman, Jeffrey D.] Oragenics Inc, Alachua, FL USA. [Calderwood, Stephen B.] Harvard Med Sch, Dept Microbiol & Mol Genet, Boston, MA USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Med Sch, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Sch Public Hlth, Dept Immunol & Infect Dis, Boston, MA USA. RP Rollins, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM srollins1@partners.org OI Rollins, Sean/0000-0002-3724-1989 FU New England Regional Center of Excellence/Biodefense and Emerging Infectious Disease Career Development Award [U54 AI057159]; [AI053442]; [N01-A1-40053]; [T32 AI07061]; [DE13523]; [U54 AI057156]; [AI33537] FX This research was supported by AI053442 and N01-A1-40053 (ETR); U54 AI057159 (SBC); T32 AI07061 (AP), a New England Regional Center of Excellence/Biodefense and Emerging Infectious Disease Career Development Award U54 AI057159 (SMR), DE13523 (MH), U54 AI057156 (TMK and CRL) and AI33537 (TMK). NR 54 TC 21 Z9 25 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 19 PY 2008 VL 3 IS 3 AR e1824 DI 10.1371/journal.pone.0001824 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370KY UT WOS:000260762300026 PM 18350160 ER PT J AU Landefeld, CS Bowers, BJ Feld, AD Hartmann, KE Hoffman, E Ingber, MJ King, JT McDougal, WS Nelson, H Orav, EJ Pignone, M Richardson, LH Rohrbaugh, RM Siebens, HC Trock, BJ AF Landefeld, C. Seth Bowers, Barbara J. Feld, Andrew D. Hartmann, Katherine E. Hoffman, Eileen Ingber, Melvin J. King, Joseph T., Jr. McDougal, W. Scott Nelson, Heidi Orav, Endel John Pignone, Michael Richardson, Lisa H. Rohrbaugh, Robert M. Siebens, Hilary C. Trock, Bruce J. TI National institutes of health state-of-the-science conference statement: Prevention of fecal and urinary incontinence in adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Wisconsin, Madison, WI USA. Univ Washington, Seattle, WA 98195 USA. Vanderbilt Inst Med & Publ Hlth, Nashville, TN USA. NYU, Sch Med, New York, NY USA. RTI Int, Washington, DC USA. Yale Univ, Sch Med, New Haven, CT USA. Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin & Mayo Grad Sch Med, Rochester, MN USA. Univ N Carolina Hosp, Chapel Hill, NC USA. Crohns Colitis Fdn Amer, Houston, TX USA. Univ Virginia, Charlottesville, VA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. OI King, Jr., Joseph/0000-0003-2823-9649; Bowers, Barbara/0000-0002-3226-0718 NR 0 TC 108 Z9 111 U1 0 U2 5 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 MAR 18 PY 2008 VL 148 IS 6 BP 449 EP 458 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 279KT UT WOS:000254354800005 PM 18268289 ER PT J AU Naik, AD Kallen, MA Walder, A Street, RL AF Naik, Aanand D. Kallen, Michael A. Walder, Annette Street, Richard L. TI Improving hypertension control in diabetes mellitus the effects of collaborative and proactive health communication SO CIRCULATION LA English DT Article DE hypertension; diabetes mellitus; physician-patient relations; outcomes assessment; goals ID TREATMENT DECISION-MAKING; BLOOD-PRESSURE CONTROL; CHRONIC ILLNESS CARE; PATIENT COMMUNICATION; SELF-MANAGEMENT; OFFICE PRACTICE; UNITED-STATES; PATIENTS WANT; PHYSICIAN; INTERVENTIONS AB Background-Communication between patients and clinicians using collaborative goals and treatment plans may overcome barriers to achieving hypertension control in routine diabetes mellitus care. We assessed the interrelation of patient-clinician communication factors to determine their independent associations with hypertension control in diabetes care. Methods and Results-We identified 566 older adults with diabetes mellitus and hypertension at the DeBakey VA Medical Center in Houston, Tex. Clinical and pharmacy data were collected, and a patient questionnaire was sent to all participants. A total of 212 individuals returned surveys. Logistic regression analyses were performed to assess the effect of patient characteristics, self-management behaviors, and communication factors on hypertension control. Three communication factors had significant associations with hypertension control. Two factors, patients' endorsement of a shared decision-making style (odds ratio 1.61, 95% confidence interval 1.01 to 2.57) and proactive communication with one's clinician about abnormal results of blood pressure self-monitoring (odds ratio 1.89, 95% confidence interval 1.10 to 3.26), had direct, independent associations in multivariate regression. Path analysis was used to investigate the direct and indirect effects of communication factors and hypertension control. Decision-making style (beta=0.20, P < 0.01) and proactive communication (beta= 0.50, P < 0.0001) again demonstrated direct effects on hypertension control. A third factor, clinicians' use of collaborative communication when setting treatment goals, had a total effect on hypertension control of 0.16 ( P < 0.05) through its direct effects on decision-making style (beta=0.28, P < 0.001) and proactive communication (beta=0.22, P < 0.01). Conclusions-Three communication factors were found to have significant associations with hypertension control. Patient - clinician communication that facilitates collaborative blood pressure goals and patients' input related to the progress of treatment may improve rates of hypertension control in diabetes care independent of medication adherence. C1 [Naik, Aanand D.; Walder, Annette; Street, Richard L.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Naik, Aanand D.] Baylor Coll Med, Sect Geriatr, Houston, TX 77030 USA. [Kallen, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX USA. [Street, Richard L.] Texas A&M Univ, Dept Commun, College Stn, TX USA. [Naik, Aanand D.; Walder, Annette; Street, Richard L.] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holocombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU NIA NIH HHS [K23 AG027144-03, 5K23AG027144, K23 AG027144] NR 48 TC 76 Z9 79 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2008 VL 117 IS 11 BP 1361 EP 1368 DI 10.1161/CIRCULATIONAHA.107.724005 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 275IN UT WOS:000254065200003 PM 18316489 ER PT J AU Kottgen, A Hwang, SJ Rampersaud, E Coresh, J North, KE Pankow, JS Meigs, JB Levy, D Boerwinkle, E Shuldiner, AR Fox, CS Kao, LW AF Kottgen, Anna Hwang, Shih-Jen Rampersaud, Evadnie Coresh, Josef North, Kari E. Pankow, James S. Meigs, James B. Levy, Daniel Boerwinkle, Eric Shuldiner, Alan R. Fox, Caroline S. Kao, Linda W. TI Variants in the transcription factor 7-like 2 gene region are associated with incident kidney disease and markers of kidney function in the atherosclerosis risk in communities study, the framingham heart study offspring cohort, and the heredity and phenotype intervention (HAPI) heart study SO CIRCULATION LA English DT Meeting Abstract CT 48th Annal Scientific Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 13-15, 2008 CL Colorado Springs, CO C1 [Kottgen, Anna; Coresh, Josef; Kao, Linda W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rampersaud, Evadnie; Shuldiner, Alan R.] Univ Maryland, Baltimore, MD 21201 USA. [North, Kari E.] Univ N Carolina, Chapel Hill, NC USA. [Pankow, James S.] Univ Minnesota, Minneapolis, MN USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2008 VL 117 IS 11 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 275IN UT WOS:000254065200041 ER PT J AU Molenaar, EA Massaro, JM Jacques, PF Pou, KM Ellison, RC Hoffmann, U Pencina, K Vasan, RS O'Donnell, CJ Fox, CS AF Molenaar, Esther A. Massaro, Joseph M. Jacques, Paul F. Pou, Karla M. Ellison, R. C. Hoffmann, Udo Pencina, Karol Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Lifestyle factors with subcutaneous and visceral adiposity: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 48th Annal Scientific Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 13-15, 2008 CL Colorado Springs, CO C1 [Molenaar, Esther A.] Univ Med Ctr Utrecht, Julius Cntr Hlth Sci & Primary Care, Utrecht, Netherlands. [Molenaar, Esther A.] Municipal Hlth Serv Utrecht, Utrecht, Netherlands. [Massaro, Joseph M.; Pencina, Karol] Boston Sch Publ Hlth, Boston, MA USA. [Jacques, Paul F.] Tufts Univ, Boston, MA 02111 USA. [Pou, Karla M.; Fox, Caroline S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ellison, R. C.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Inst Framingham Heart Study, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2008 VL 117 IS 11 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 275IN UT WOS:000254065200093 ER PT J AU Shlipak, MG Katz, R Fried, L Kestenbaum, B Siscovick, D Sarnak, M AF Shlipak, Michael G. Katz, Ronit Fried, Linda Kestenbaum, Bryan Siscovick, David Sarnak, Mark TI Clinical and subclinical cardiovascular disease and kidney function decline in the elderly SO CIRCULATION LA English DT Meeting Abstract CT 48th Annal Scientific Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 13-15, 2008 CL Colorado Springs, CO C1 [Shlipak, Michael G.] San Francisco VA Med Cntr, San Francisco, CA USA. [Katz, Ronit; Siscovick, David] Univ Washington, Seattle, WA 98195 USA. [Fried, Linda] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kestenbaum, Bryan] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Sarnak, Mark] Tufts New England Med Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2008 VL 117 IS 11 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 275IN UT WOS:000254065200043 ER PT J AU Teerlink, JR AF Teerlink, John R. TI Learning the points of COMPASS-HF - Assessing implantable hemodynamic monitoring in heart failure patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID PRECEDING HOSPITALIZATION; TRIAL; MULTICENTER; OUTCOMES C1 [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol Sect, Cardiol 111C,4150 Clement St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Teerlink, John/D-2986-2012 NR 18 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 18 PY 2008 VL 51 IS 11 BP 1080 EP 1082 DI 10.1016/j.jacc.2007.12.009 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 275HS UT WOS:000254063100005 PM 18342225 ER PT J AU Metzler, RA Kim, IW Delak, K Evans, JS Zhou, D Beniash, E Wilt, F Abrecht, M Chiou, JW Guo, JH Coppersmith, SN Gilbert, PUPA AF Metzler, Rebecca A. Kim, Il Won Delak, Katya Evans, John Spencer Zhou, Dong Beniash, Elia Wilt, Fred Abrecht, Mike Chiou, Jau-Wern Guo, Jinghua Coppersmith, Susan N. Gilbert, P. U. P. A. TI Probing the organic-mineral interface at the molecular level in model biominerals SO LANGMUIR LA English DT Article ID SPICULE MATRIX PROTEIN; URCHIN EMBRYO SPICULE; SOLID-STATE NMR; SHELL PROTEIN; IN-VITRO; X-PEEM; HYDROXYAPATITE; GROWTH; IDENTIFICATION; SPECTROSCOPY AB It is widely known that macromolecules, such as proteins, can control the nucleation and growth of inorganic solids in biomineralizing organisms. However, what is not known are the complementary molecular interactions, organization, and rearrangements that occur when proteins interact with inorganic solids during the formation of biominerals. The organic-mineral interface (OMI) is expected to be the site for these phenomena, and is therefore extraordinarily interesting to investigate. In this report, we employ X-ray absorption near edge (XANES) spectromicroscopy to investigate the electronic structure of both calcium carbonate mineral crystals and polypeptides, and detect changing bonds at the OMI during crystal growth in the presence of polypeptides. We acquired XANES spectra from calcium carbonate crystals grown in the presence of three mollusk nacre-associated polypeptides (AP7N, AP24N, n16N) and in the presence of a sea urchin spicule matrix protein, LSM34. All these model biominerals gave similar results, including the disruption of CO bonds in calcite and enhancement of the peaks associated with C-H bonds and C-O bonds in peptides, indicating ordering of the amino acid side chains in the mineral-associated polypeptides and carboxylate binding. This is the first evidence of the mutual effect of calcite on peptide chain and peptide chain on calcite during biomineralization. We also show that these changes do not occur when Asp and Glu are replaced in the n16N sequence with Asn and Gln, respectively, demonstrating that carboxyl groups in Asp and Glu do participate in polypeptide-mineral molecular associations. C1 [Metzler, Rebecca A.; Zhou, Dong; Coppersmith, Susan N.; Gilbert, P. U. P. A.] Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. [Kim, Il Won; Delak, Katya; Evans, John Spencer] NYU, Chem Phys Lab, Ctr Biomol Mat Spectroscopy, New York, NY 10010 USA. [Beniash, Elia] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. [Wilt, Fred] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Abrecht, Mike] Univ Wisconsin, Ctr Synchrotron Radiat, Stoughton, WI 53589 USA. [Chiou, Jau-Wern] Natl Univ Kaohsiung, Dept Appl Phys, Kaohsiung 81148, Taiwan. [Guo, Jinghua] Univ Calif Berkeley, Lawrence Berkeley Lab, Adv Light Source, Berkeley, CA 94720 USA. RP Gilbert, PUPA (reprint author), Univ Wisconsin, Dept Phys, 1150 Univ Ave, Madison, WI 53706 USA. EM pupa@physics.wisc.edu RI Zhou, Dong/A-2675-2011; Gilbert, Pupa/A-6299-2010 OI Gilbert, Pupa/0000-0002-0139-2099 NR 45 TC 50 Z9 50 U1 2 U2 52 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 18 PY 2008 VL 24 IS 6 BP 2680 EP 2687 DI 10.1021/la7031237 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 273OM UT WOS:000253941000060 PM 18251561 ER PT J AU Wills, AM Landers, JE Zhang, H Richter, RJ Caraganis, AJ Cudkowicz, ME Furlong, CE Brown, RH AF Wills, A. -M. Landers, J. E. Zhang, H. Richter, R. J. Caraganis, A. J. Cudkowicz, M. E. Furlong, C. E. Brown, R. H., Jr. TI Paraoxonase 1 (PON1) organophosphate hydrolysis is not reduced in ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN SERUM PARAOXONASE; SPORADIC ALS; POLYMORPHISMS; GENE; ASSOCIATION; DISEASE; SUSCEPTIBILITY; EXPRESSION; DIAGNOSIS AB Objective: Four recent studies report a genetic association of the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). We tested the hypothesis that this association correlates with functional changes in paraoxonase 1 (PON1, MIM 168820). Methods: Sera from 140 ALS participants; 153 age-, race-, and sex-matched controls; and 30 matched CSF samples were tested for paraoxonase, diazoxonase, and arylesterase activities. Participants with ALS were genotyped using tagging single nucleotide polymorphisms across the PON locus. Survival data and enzyme activity were correlated with genotype. Results: There was a trend toward increased paraoxonase activity in ALS compared with controls (mean control paraoxonase 701.9 +/- 469.7 U/L, mean ALS 792.5 +/- 574.1 U/L; p = 0.066 after correction) which correlated with increased frequency of the homozygous arginine (RR) variant of PON1(Q192R) (p = 0.004). There was no significant difference in PON1 protein levels, or arylesterase or diazoxonase activities. Organophosphate hydrolysis rates had no effect on ALS survival. Conclusions: Contrary to expectations, PON1 protein, paraoxonase, diazoxonase, and arylesterase activities were not reduced in amyotrophic lateral sclerosis (ALS). The increase in PON1(R192) frequency in ALS in our study supports previous genetic susceptibility studies. Our findings suggest that the influence of PON1 polymorphisms on ALS susceptibility is not due to reduced organophosphate hydrolysis. C1 [Wills, A. -M.; Landers, J. E.; Brown, R. H., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Day Neuromuscular Res Lab, Boston, MA 02115 USA. [Zhang, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02115 USA. [Caraganis, A. J.; Cudkowicz, M. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurol Clin Trials Unit, Boston, MA 02115 USA. [Richter, R. J.; Furlong, C. E.] Univ Washington, Div Med Genet, Dept Genome Sci & Med, Seattle, WA 98195 USA. RP Wills, AM (reprint author), CNY 114-3125,114 16th St, Charlestown, MA 02129 USA. EM awills@partners.org FU NIEHS NIH HHS [ES09883, ES04696]; NINDS NIH HHS [5R01NS05050641-04, 5R01NS050557-02] NR 35 TC 15 Z9 16 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 MAR 18 PY 2008 VL 70 IS 12 BP 929 EP 934 DI 10.1212/01.wnl.0000305956.37931.dd PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 275IQ UT WOS:000254065500006 PM 18347314 ER PT J AU Schur, EA Cummings, DE Callahan, HS Foster-Schubert, KE AF Schur, Ellen A. Cummings, David E. Callahan, Holly S. Foster-Schubert, Karen E. TI Association of cognitive restraint with ghrelin, leptin, and insulin levels in subjects who are not weight-reduced SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE restraint; ghrelin; leptin; insulin; obesity; body weight; eating disorders; appetite regulation ID 3-FACTOR EATING QUESTIONNAIRE; PLASMA GHRELIN; DIETARY RESTRAINT; ANOREXIA-NERVOSA; SERUM LEPTIN; BODY-WEIGHT; ENERGY-EXPENDITURE; PHYSICAL-ACTIVITY; OBESE HUMANS; WOMEN AB Despite widespread efforts at weight loss, the prevalence of obesity continues to rise. Restrained eating is a pattern of attempted weight control characterized by cognitive restriction of food intake that has paradoxically been linked with overeating and/or weight gain. It is not known whether restrained eating is associated with abnormalities in appetite-regulating hormones, independent of its effects on body weight. To address this question, we assessed cognitive restraint using the Three-Factor Eating Questionnaire and obtained fasting measurements of ghrelin, leptin and insulin from 24 healthy, non-obese (body mass index (BMI) 19.7 to 29.6 kg/m(2)) adult subjects who were at a stable, lifetime maximum weight. We chose to study subjects at stable maximum weight to avoid the secondary effects of weight reduction on body-weight regulating hormones. Subjects were classified by cognitive restraint scale score into Low, Indeterminate, and High Restraint groups. Higher ghrelin levels were significantly associated with restraint in an unadjusted model (P=0.004) and after adjustment for BMI (P=0.007). No relationships were found between restraint scores and either leptin (P=0.75) or insulin (P=0.36). These findings show an orexigenic hormonal profile in restrained eaters, independent of changes in body weight. (c) 2007 Elsevier Inc. All rights reserved. C1 [Schur, Ellen A.] Univ Washington, Harborview Med Ctr, Div Gen Internal Med, Seattle, WA 98104 USA. [Cummings, David E.; Foster-Schubert, Karen E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. [Callahan, Holly S.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Callahan, Holly S.] Univ Washington, Sch Med, Seattle, WA 98104 USA. RP Schur, EA (reprint author), Univ Washington, Harborview Med Ctr, Div Gen Internal Med, Box 359780,325 9th Ave, Seattle, WA 98104 USA. EM ellschur@u.washington.edu FU NCRR NIH HHS [M01 RR000037, K12 RR023265, 5K12RR023265, M01RR-00037]; NIDDK NIH HHS [K23 DK070826-01, P30 DK035816, DK-35816, R01 DK61516, K23 DK070826, R01 DK061516] NR 60 TC 26 Z9 26 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAR 18 PY 2008 VL 93 IS 4-5 BP 706 EP 712 DI 10.1016/j.physbeh.2007.11.025 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 293BZ UT WOS:000255311100006 PM 18164043 ER PT J AU Zhang, S Metelev, V Tabatadze, D Zamecnik, PC Bogdanov, A AF Zhang, Surong Metelev, Valeri Tabatadze, David Zamecnik, Paul C. Bogdanov, Alexei, Jr. TI Fluorescence resonance energy transfer in near-infrared fluorescent oligonucleoticle probes for detecting protein-DNA interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE carbocyanine; transcription factor ID NF-KAPPA-B; MOLECULAR BEACONS; BINDING PROTEIN; ANTISENSE OLIGONUCLEOTIDES; APTAMER BEACONS; CANCER-THERAPY; CELL LINES; P50; HYBRIDIZATION; RECOGNITION AB Optical imaging in the near-infrared (NIR) range enables detecting ligand-receptor interactions and enzymatic activity in vivo due to lower scattering and absorption of NIR photons in the tissue. We designed and tested prototype NIR fluorescent oligodeoxyribo-nucleotide (ODN) reporters that can sense transcription factor NF-kappa B p50 protein binding. The reporter duplexes included donor NIR Cy5.5 indodicarbocyanine fluorochrome linked to the 3' end of the first ODN and NIR acceptor fluorochromes (indodicarbocyanine Cy7 or, alternatively, a heptamethine cyanine IRDye 800CW) that were linked at the positions +8 and +12 to the complementary ODN that encoded p50 binding sites. Both Cy7 and 800CW fluorochromes were linked by using hydrophilic internucleoside phosphate linkers that enable interaction between the donor and the acceptor with no base-pairing interference. We observed efficient fluorescence resonance energy transfer (FRET) both in the case of Cy5.5-Cy7 and Cy5.5-800CW pairs of fluorochromes, which was sensitive to the relative position of the dyes. Higher FRET efficiency observed in the case of Cy5.5-Cy7 pair was due to a larger overlap between the ODN-linked Cy5.5 emission and Cy7 excitation spectra. Fluorescent mobility shift assay showed that the addition of human recombinant p50 to ODN duplexes resulted in p50 binding and measurable increase of Cy5.5 emission. In addition, p50 binding provided a concomitant protection of FRET effect from exonuclease-mediated hydrolysis. We conclude that NIR FRET effect can be potentially used for detecting protein-DNA interactions and that the feasibility of detection depends on FRET efficacy and relative fluorochrome positions within ODN binding sites. C1 [Zhang, Surong; Metelev, Valeri; Bogdanov, Alexei, Jr.] Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Dept Radiol, Worcester, MA 01655 USA. [Bogdanov, Alexei, Jr.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. [Tabatadze, David; Zamecnik, Paul C.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Metelev, Valeri] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia. RP Bogdanov, A (reprint author), Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM alexei.bogdanov@umassmed.edu RI Metelev, Valeri/I-3238-2012 FU NCI NIH HHS [R33 CA134385-01, R21 CA116144, R33 CA134385]; NIAID NIH HHS [5 R01 AI060872-02, R01 AI060872] NR 34 TC 35 Z9 37 U1 5 U2 32 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 MAR 18 PY 2008 VL 105 IS 11 BP 4156 EP 4161 DI 10.1073/pnas.0800162105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278DH UT WOS:000254263300017 PM 18337505 ER PT J AU David, G Grandinetti, KB Finnerty, PM Simpson, N Chu, GC DePinho, RA AF David, Gregory Grandinetti, Kathryn B. Finnerty, Patricia M. Simpson, Natalie Chu, Gerald C. DePinho, Ronald A. TI Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE E2F; histone deacetylase; knockout; quiescence ID HISTONE DEACETYLASE COMPLEX; RETINOBLASTOMA GENE FAMILY; COREPRESSOR COMPLEX; OVERLAPPING INTERESTS; TARGETED DISRUPTION; INTEGRAL COMPONENT; G(1) CONTROL; IN-VIVO; PROTEIN; REPRESSION AB The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B, which serve as scaffolds tethering HDAC enzymatic activity, and numerous sequence-specific transcription factors to enable local chromatin regulation at specific gene targets. Despite broad overlapping expression of mSin3A and mSin3B, mSin3A is cell-essential and vital for early embryonic development. Here, genetic disruption of mSin3B reveals a very different phenotype characterized by the survival of cultured cells and lethality at late stages of embryonic development with defective differentiation of multiple lineages-phenotypes that are strikingly reminiscent of those associated with loss of retinoblastoma family members or E2F transcriptional repressors. Additionally, we observe that, whereas mSin3B(-/-) cells cycle normally under standard growth conditions, they show an impaired ability to exit the cell cycle with limiting growth factors. Correspondingly, mSin3B interacts physically with the promoters of known E2F target genes, and its deficiency is associated with derepression of these gene targets in vivo. Together, these results reveal a critical role for mSin3B in the control of cell cycle exit and terminal differentiation in mammals and establish contrasting roles for the mSin3 proteins in the growth and development of specific lineages. C1 [David, Gregory; Grandinetti, Kathryn B.; Finnerty, Patricia M.; Simpson, Natalie] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. [David, Gregory] NYU, Sch Med, Inst Canc, New York, NY 10016 USA. [David, Gregory; Chu, Gerald C.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Fdn Inst Innovat Canc Sc, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. [Chu, Gerald C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP David, G (reprint author), NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. EM gregory.david@med.nyu.edu; ron_depinho@dfci.harvard.edu OI , gregory/0000-0002-3371-4558 FU NCI NIH HHS [T32 CA009161, CA009161, R01 CA086379, R01CA86379]; NIGMS NIH HHS [GM066704, T32 GM066704] NR 30 TC 58 Z9 58 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2008 VL 105 IS 11 BP 4168 EP 4172 DI 10.1073/pnas.0710285105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278DH UT WOS:000254263300019 PM 18332431 ER PT J AU Sun, L Vukicevic, S Baliram, R Yang, G Sendak, R McPherson, J Zhu, LL Iqbal, J Latif, R Natrajan, A Arabi, A Yamoah, K Moonga, BS Gabet, Y Davies, TF Bab, I Abe, E Sampath, K Zaidi, M AF Sun, Li Vukicevic, Slobodan Baliram, Ramkumarie Yang, Guozhe Sendak, Rebecca McPherson, John Zhu, Ling-Ling Iqbal, Jameel Latif, Rauf Natrajan, Arjun Arabi, Ario Yamoah, Kosj Moonga, Baljit S. Gabet, Yankel Davies, Terry F. Bab, Itai Abe, Etsuko Sampath, Kuber Zaidi, Mone TI Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE osteoclast; osteoporosis; pituitary; osteoblast; bisphosphonate ID THYROID-STIMULATING HORMONE; HYPERTHYROIDISM; OSTEOPOROSIS; FRACTURE; WOMEN; RISK AB We recently described the direct effects of thyroid-stimulating hormone (TSH) on bone and suggested that the bone loss in hyperthyroidism, hitherto attributed solely to elevated thyroid hormone levels, could at least in part arise from accompanying decrements in serum TSH. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton. Here, we show that TSH, when injected intermittently into rodents, even at intervals of 2 weeks, displays a powerful antiresorptive action in vivo. By virtue of this action, together with the possible anabolic effects shown earlier, TSH both prevents bone loss and restores the lost bone after ovariectomy. Importantly, the osteoclast inhibitory action of TSH persists ex vivo even after therapy is stopped for 4 weeks. This profound and lasting antiresorptive action of TSH is mimicked in cells that genetically overexpress the constitutively active ligand-independent TSH receptor (TSHR). In contrast, loss of function of a mutant TSHR (Pro -> Leu at 556) in congenital hypothyroid mice activates osteoclast differentiation, confirming once again our premise that TSHRs have a critical role in regulating bone remodeling. C1 [Sun, Li; Baliram, Ramkumarie; Yang, Guozhe; Zhu, Ling-Ling; Iqbal, Jameel; Latif, Rauf; Natrajan, Arjun; Arabi, Ario; Yamoah, Kosj; Moonga, Baljit S.; Davies, Terry F.; Abe, Etsuko; Zaidi, Mone] Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Mt Sinai Bone Program, New York, NY 10029 USA. [Sun, Li; Baliram, Ramkumarie; Yang, Guozhe; Zhu, Ling-Ling; Iqbal, Jameel; Latif, Rauf; Natrajan, Arjun; Arabi, Ario; Yamoah, Kosj; Moonga, Baljit S.; Davies, Terry F.; Abe, Etsuko; Zaidi, Mone] Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Thyroid Res Unit, New York, NY 10029 USA. [Vukicevic, Slobodan; McPherson, John] Lab Mineralized Tissues, Zagreb 10000, Croatia. [Sendak, Rebecca] Genzyme Corp, Framingham, MA 02142 USA. [Gabet, Yankel; Bab, Itai] Hebrew Univ Jerusalem, Bone Lab, IL-91904 Jerusalem, Israel. RP Zaidi, M (reprint author), Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Mt Sinai Bone Program, New York, NY 10029 USA. EM mone.zaidi@mountsinai.org FU NIA NIH HHS [AG23176, R01 AG012951, R01 AG023176, AG14917, AG12951]; NIDDK NIH HHS [DK70526, R01 DK070526] NR 24 TC 51 Z9 55 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2008 VL 105 IS 11 BP 4289 EP 4294 DI 10.1073/pnas.0712395105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278DH UT WOS:000254263300040 PM 18332426 ER PT J AU Gold, B Kirchhoff, T Stefanov, S Lautenberger, J Viale, A Garber, J Friedman, E Narod, S Olshen, AB Gregersen, P Kosarin, K Olsh, A Bergeron, J Ellis, NA Klein, RJ Clark, AG Norton, L Dean, M Boyd, J Offit, K AF Gold, Bert Kirchhoff, Tomas Stefanov, Stefan Lautenberger, James Viale, Agnes Garber, Judy Friedman, Eitan Narod, Steven Olshen, Adam B. Gregersen, Peter Kosarin, Kristi Olsh, Adam Bergeron, Julie Ellis, Nathan A. Klein, Robert J. Clark, Andrew G. Norton, Larry Dean, Michael Boyd, Jeff Offit, Kenneth TI Genome-wide association study provides evidence for a breast cancer risk locus at 6q22-33 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genomics; mapping; disease; predisposition; SNP ID SUSCEPTIBILITY GENE; CHROMOSOME 8P12-P22; LINKAGE ANALYSIS; FAMILY HISTORY; POLYMORPHISMS; INHIBITION; APOPTOSIS; CELLS AB We performed a three-phase genome-wide association study (GWAS) using cases and controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify loci associated with breast cancer risk. In the first phase, we compared allele frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ familial cases and 299 cancer-free AJ controls using chi(2) and the Cochran-Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions most significantly associated from stage 1, including 4 SNPs from the FGFR2 region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ controls. We replicated major associations in a third independent set of 243 AJ cases and 187 controls. We obtained a significant allele P value of association with AJ breast cancer in the FGFR2 region (P = 1.5 x 10(-5), odds ratio (OR) 1.26, 95% confidence interval (CI) 1.13-1.40 at rs1078806 for all phases combined). In addition, we found a risk locus in a region of chromosome 6q22.33 (P = 2.9 x 10(-8), OR 1.41, 95% Cl 1.25-1.59 at rs2180341). Using several SNPs at each implicated locus, we were able to verify associations and impute haplotypes. The major haplotype at the 6q22.33 locus conferred protection from disease, whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region include ECHDC1, which encodes a protein involved in mitochondrial fatty acid oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known pathways in breast cancer pathogenesis. C1 [Kirchhoff, Tomas; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY 10065 USA. [Gold, Bert; Stefanov, Stefan; Lautenberger, James; Olsh, Adam; Dean, Michael] NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. [Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genome Core Lab, New York, NY 10065 USA. [Norton, Larry] Mem Sloan Kettering Canc Ctr, Breast Med Serv, New York, NY 10065 USA. [Olshen, Adam B.] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10065 USA. [Klein, Robert J.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. [Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. [Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Narod, Steven] Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. [Gregersen, Peter] N Shore Long Isl Jewish Res Inst, Ctr Genom & Human Genet, Manhasset, NY 11030 USA. [Bergeron, Julie] SAIC Frederick Inc, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. [Ellis, Nathan A.] Univ Chicago, Dept Med, Div Gastroenterol, Chicago, IL 60637 USA. [Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. [Boyd, Jeff] Mem Hlth Univ Med Ctr, Anderson Canc Inst, Savannah, GA 31404 USA. RP Offit, K (reprint author), Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM offitk@mskcc.org RI Dean, Michael/G-8172-2012; Klein, Robert/K-1888-2013; OI Dean, Michael/0000-0003-2234-0631; Klein, Robert/0000-0003-3539-5391; Norton, Larry/0000-0003-3701-9250; Kirchhoff, Tomas/0000-0002-9055-2364 NR 31 TC 213 Z9 224 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2008 VL 105 IS 11 BP 4340 EP 4345 DI 10.1073/pnas.0800441105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278DH UT WOS:000254263300049 PM 18326623 ER PT J AU Ha, SJ Mueller, SN Wherry, EJ Barber, DL Aubert, RD Sharpe, AH Freeman, GJ Ahmed, R AF Ha, Sang-Jun Mueller, Scott N. Wherry, E. John Barber, Daniel L. Aubert, Rachael D. Sharpe, Arlene H. Freeman, Gordon J. Ahmed, Rafi TI Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CD8 T-CELLS; C VIRUS-INFECTION; CHRONIC VIRAL-INFECTION; CHRONIC HEPATITIS-C; HCV INFECTION; B-VIRUS; SIVMAC251 INFECTION; DISEASE PROGRESSION; CD127 EXPRESSION; INTERFERON-ALPHA AB Therapeutic vaccination is a potentially promising strategy to enhance T cell immunity and viral control in chronically infected individuals. However, therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral T cell responses has not always been observed. One of the principal reasons for the limited success of therapeutic vaccination is that virus-specific T cells become functionally exhausted during chronic infections. We now provide a novel strategy for enhancing the efficacy of therapeutic vaccines. In this study, we show that blocking programmed death (PD)-1/PD-L1 inhibitory signals on exhausted CD8(+) T cells, in combination with therapeutic vaccination, synergistically enhances functional CD8(+) T cell responses and improves viral control in mice chronically infected with lymphocytic choriomeningitis virus. This combinatorial therapeutic vaccination was effective even in the absence of CD4(+) T cell help. Thus, our study defines a potent new approach to augment the efficacy of therapeutic vaccination by blocking negative signals. Such an approach may have broad applications in developing treatment strategies for chronic infections in general, and perhaps also for tumors. C1 [Ha, Sang-Jun; Mueller, Scott N.; Wherry, E. John; Barber, Daniel L.; Aubert, Rachael D.; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Ha, Sang-Jun; Mueller, Scott N.; Wherry, E. John; Barber, Daniel L.; Aubert, Rachael D.; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM ra@microbio.emory.edu RI Mueller, Scott/B-1918-2012; OI Mueller, Scott/0000-0002-3838-3989; Ha, Sang-Jun/0000-0002-1192-6031 FU NIAID NIH HHS [AI30048, AI56299, N01AI30048, P01 AI056299] NR 48 TC 129 Z9 137 U1 1 U2 9 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 MAR 17 PY 2008 VL 205 IS 3 BP 543 EP 555 DI 10.1084/jem.20071949 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 276VZ UT WOS:000254173100006 PM 18332181 ER PT J AU Franco, S Murphy, MM Li, G Borjeson, T Boboila, C Alt, FW AF Franco, Sonia Murphy, Michael M. Li, Gang Borjeson, Tiffany Boboila, Cristian Alt, Frederick W. TI DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEPENDENT PROTEIN-KINASE; B-CELL DEVELOPMENT; V(D)J RECOMBINATION; GENOMIC INSTABILITY; INDEPENDENT FUNCTIONS; CHROMOSOME BREAKS; CATALYTIC SUBUNIT; ATM; DEFICIENT; REPAIR AB The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Artemis are classical nonhomologous DNA end-joining (C-NHEJ) factors required for joining a subset of DNA double-strand breaks (DSB), particularly those requiring end processing. In mature B cells, activation-induced cytidine deaminase (AID) initiates class switch recombination (CSR) by introducing lesions into S regions upstream of two recombining C-H exons, which are processed into DSBs and rejoined by C-NHEJ to complete CSR. The function of DNA-PKcs in CSR has been controversial with some reports but not others showing that DNA-PKcs-deficient mice are significantly impaired for CSR. Artemis-deficient B cells reportedly undergo CSR at normal levels. Overall, it is still not known whether there are any CSR-associated DSBs that require DNA-PKcs and/or Artemis to be joined. Here, we have used an immunoglobulin (Ig)H locus-specific fluorescent in situ hybridization assay to unequivocally demonstrate that both DNA-PKcs and, unexpectedly, Artemis are necessary for joining a subset of AID-dependent DSBs. In the absence of either factor, B cells activated for CSR frequently generate AID-dependent IgH locus chromosomal breaks and translocations. We also find that under specific activation conditions, DNA-PKcs(-/-) B cells with chromosomal breaks are eliminated or at least prevented from progressing to metaphase via a p53-dependent response. C1 [Alt, Frederick W.] Harvard Univ, Childrens Hosp, Howard Hughes Med Inst, Dept Genet,Sch Med, Boston, MA 02115 USA. Immune Dis Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Howard Hughes Med Inst, Dept Genet,Sch Med, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [T32 CA09382, CA92625, P01 CA092625, T32 CA009382]; NIAID NIH HHS [AI31541, AI35714, P01 AI031541, P01 AI035714, U19 AI031541] NR 48 TC 48 Z9 48 U1 0 U2 0 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 MAR 17 PY 2008 VL 205 IS 3 BP 557 EP 564 DI 10.1084/jem.20080044 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 276VZ UT WOS:000254173100007 PM 18316419 ER PT J AU Haxhinasto, S Mathis, D Benoist, C AF Haxhinasto, Sokol Mathis, Diane Benoist, Christophe TI The AKT-mTOR axis regulates de novo differentiation of CD4(+)Foxp3(+) cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; IN-VIVO EXPANSION; T-CELLS; THYMIC SELECTION; TGF-BETA; PROTEIN-KINASE; SELF-TOLERANCE; CUTTING EDGE; RECEPTOR; AUTOIMMUNITY AB CD4(+)Foxp3(+) regulatory T (T reg) cells play an essential role in maintaining immunological tolerance via their suppressive function on conventional CD4(+) T (Tconv) cells. Repertoire studies suggest that distinct T cell receptor signaling pathways lead to T reg differentiation, but the signals that regulate T reg specification are largely unknown. We identify AKT as a strong repressor of entry into the T reg phenotype in vitro and in vivo. A constitutively active allele of AKT substantially diminished TGF-beta-induced Foxp3 expression in a kinase-dependent manner and via a rapamycin-sensitive pathway, implicating the AKT-mammalian target of rapamycin axis. The observed impairment in Foxp3 induction was part of a broad dampening of the typical T reg transcriptional signature. Expression of active AKT at a stage before Foxp3 turn on during normal T reg differentiation in the thymus selectively impaired differentiation of CD4(+)Foxp3(+) cells without any alteration in the positive selection of Tconv. Activated AKT, in contrast, did not affect established Foxp3 expression in T reg cells. These results place AKT at a nexus of signaling pathways whose proper activation has a strong and broad impact on the onset of T reg specification. C1 [Haxhinasto, Sokol; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. [Haxhinasto, Sokol; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIAID NIH HHS [1R01AI51530, R01 AI051530] NR 66 TC 391 Z9 403 U1 0 U2 15 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 MAR 17 PY 2008 VL 205 IS 3 BP 565 EP 574 DI 10.1084/jem.20071477 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 276VZ UT WOS:000254173100008 PM 18283119 ER PT J AU Cantor, AB Iwasaki, H Arinobu, Y Moran, TB Shigematsu, H Sullivan, MR Akashi, K Orkin, SH AF Cantor, Alan B. Iwasaki, Hirorni Arinobu, Yojiro Moran, Tyler B. Shigematsu, Hirokazu Sullivan, Matthew R. Akashi, Koichi Orkin, Stuart H. TI Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; FC-EPSILON-RI; ZINC-FINGER PROTEIN; ERYTHROID GENE-EXPRESSION; EOSINOPHIL LINEAGE; IN-VIVO; MEGAKARYOCYTIC DIFFERENTIATION; COMMITTED PROGENITORS; HEART MORPHOGENESIS; CATALYTIC DOMAIN AB The zinc finger transcription factor GATA-1 requires direct physical interaction with the cofactor friend of GATA-1 (FOG-1) for its essential role in erythroid and megakaryocytic development. We show that in the mast cell lineage, GATA-1 functions completely independent of FOG proteins. Moreover, we demonstrate that FOG-1 antagonizes the fate choice of multipotential progenitor cells for the mast cell lineage, and that its down-regulation is a prerequisite for mast cell development. Remarkably, ectopic expression of FOG-1 in committed mast cell progenitors redirects them into the erythroid, megakaryocytic, and granulocytic lineages. These lineage switches correlate with transcriptional down-regulation of GATA-2, an essential mast cell GATA factor, via switching of GATA-1 for GATA-2 at a key enhancer element upstream of the GATA-2 gene. These findings illustrate combinatorial control of cell fate identity by a transcription factor and its cofactor, and highlight the role of transcriptional networks in lineage determination. They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment. C1 [Cantor, Alan B.; Moran, Tyler B.; Sullivan, Matthew R.; Orkin, Stuart H.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Cantor, Alan B.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Arinobu, Yojiro; Shigematsu, Hirokazu; Akashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Internal Med, Boston, MA 02115 USA. [Iwasaki, Hirorni; Akashi, Koichi] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Cantor, AB (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [K08 CA082175, K08 CA82175]; NHLBI NIH HHS [R01 HL075705] NR 74 TC 53 Z9 54 U1 0 U2 0 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 MAR 17 PY 2008 VL 205 IS 3 BP 611 EP 624 DI 10.1084/jem.20070544 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 276VZ UT WOS:000254173100012 PM 18299398 ER PT J AU Sarkar, S Kalia, V Haining, WN Konieczny, BT Subramaniam, S Ahmed, R AF Sarkar, Surojit Kalia, Vandana Haining, W. Nicholas Konieczny, Bogumila T. Subramaniam, Shruti Ahmed, Rafi TI Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IL-7 RECEPTOR-ALPHA; CUTTING EDGE; CLONAL EXPANSION; VIRAL-INFECTION; IMMUNOLOGICAL MEMORY; PROTECTIVE IMMUNITY; LYMPHOCYTE RESPONSES; SELECTIVE EXPRESSION; LINEAGE RELATIONSHIP; IN-VIVO AB An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study, we provide a comprehensive phenotypic, functional, and genomic profiling of terminal effectors and memory precursors. Using killer cell lectin-like receptor G1 as a marker to distinguish these effector subsets, we found that despite their diverse cell fates, both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making interleukin (IL) 2, thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid recall responses. Experiments to understand the signals that regulate the generation of terminal effectors versus memory precursors showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation toward the tail end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation. C1 [Sarkar, Surojit; Kalia, Vandana; Konieczny, Bogumila T.; Subramaniam, Shruti; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Haining, W. Nicholas] Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM ra@microbio.emory.edu FU NIAID NIH HHS [AI30048, N01AI30048] NR 70 TC 300 Z9 302 U1 1 U2 10 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 MAR 17 PY 2008 VL 205 IS 3 BP 625 EP 640 DI 10.1084/jem.20071641 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 276VZ UT WOS:000254173100013 PM 18316415 ER PT J AU Miret, J Nascimento, E Sampaio, W Franca, JC Fujiwara, RT Vale, A Dias, ES Vieira, E da Costa, RT Mayrink, W Neto, AC Reed, S AF Miret, Jorge Nascimento, Evaldo Sampaio, Weverton Franca, Joao Carlos Fujiwara, Ricardo Toshio Vale, Andre Dias, Edelberto Santos Vieira, Edva da Costa, Roberto Teodoro Mayrink, Wilson Neto, Antonio Campos Reed, Steven TI Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime (R)) and the recombinant Leish-110f (R)+MPL-SE (R) vaccine to treat canine visceral leishmaniasis SO VACCINE LA English DT Article DE Leishmania chagasi; leishmaniasis; canine visceral leishmaniasis; immunochemotherapy ID DIFFERENT CLINICAL FORMS; FOLLOW-UP; SODIUM STIBOGLUCONATE; INFANTUM INFECTION; IMMUNE-RESPONSES; CYTOKINE PROFILE; DOGS; IMMUNOTHERAPY; CHEMOTHERAPY; ANTIGEN AB The evaluation of the efficacy of an immunochemotherapy protocol to treat symptomatic dogs naturally infected with Leishmania chagasi was studied. This clinical trial had the purpose to test the combination of N-methyl meglumine antimoniate (Glucantime (R)) and the second generation recombinant vaccine Leish-110f (R) plus the adjuvant MPL-SE (R) to treat the canine leishmaniasis (CanL). Thirty symptomatic naturally infected mongrel dogs were divided into five groups. Animals received standard treatment with Glucantime (R) or treatment with Glucantime (R)/Leish-110f (R)+MPL-SE (R) as immunochemotherapy protocol. Additional groups received Leish-110f (R)+MPL-SE (R) only, MPL-SE (R) only, or placebo. Evaluation of haematological, biochemical (renal and hepatic function) and plasmatic proteins, immunological (humoral and cellular immune response) and the parasitological test revealed improvement of the clinical parameters and parasitological cure in dogs in both chemotherapy atone and immunochemotherapy cohorts. However, the immunotherapy and immunochemotherapy cohorts had reduced number of deaths, higher survival probability, and specific cellular reactivity to leishmanial antigens, in comparison with chemotherapy cohort only and control groups (adjuvant atone and placebo). These results support the notion of using well-characterized recombinant vaccine as an adjunct to improve the current chemotherapy of CanL. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Miret, Jorge; Nascimento, Evaldo; Sampaio, Weverton; Franca, Joao Carlos; Fujiwara, Ricardo Toshio; Vale, Andre; da Costa, Roberto Teodoro; Mayrink, Wilson] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Lab Leishmanioses & Vacinas, BR-31270901 Belo Horizonte, MG, Brazil. [Fujiwara, Ricardo Toshio; Dias, Edelberto Santos] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [Neto, Antonio Campos] Forsyth Inst, Boston, MA USA. [Reed, Steven] Infect Dis Res Inst, Seattle, WA USA. RP Nascimento, E (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Lab Leishmanioses & Vacinas, Avenida Antonio Carlos 6627,Pampulha, BR-31270901 Belo Horizonte, MG, Brazil. EM evaldo@icb.ufmg.br RI Fujiwara, Ricardo/J-7579-2012 OI Fujiwara, Ricardo/0000-0002-4713-575X NR 62 TC 35 Z9 35 U1 0 U2 3 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 MAR 17 PY 2008 VL 26 IS 12 BP 1585 EP 1594 DI 10.1016/j.vaccine.2008.01.026 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 282UL UT WOS:000254592600009 PM 18328956 ER PT J AU Lin, HH Ray, S Tongchusak, S Reinherz, EL Brusic, V AF Lin, Hong Huang Ray, Surajit Tongchusak, Songsak Reinherz, Ellis L. Brusic, Vladimir TI Evaluation of MHC class I peptide binding prediction servers: Applications for vaccine research SO BMC IMMUNOLOGY LA English DT Article ID T-CELL EPITOPES; INDEPENDENT BINDING; ANTIGENIC PEPTIDES; OVARIAN-CANCER; MOLECULES; SYSTEM; HLA; IDENTIFICATION; DISCOVERY; CARCINOMA AB Background: Protein antigens and their specific epitopes are formulation targets for epitope-based vaccines. A number of prediction servers are available for identification of peptides that bind major histocompatibility complex class I (MHC-I) molecules. The lack of standardized methodology and large number of human MHC-I molecules make the selection of appropriate prediction servers difficult. This study reports a comparative evaluation of thirty prediction servers for seven human MHC-I molecules. Results: Of 147 individual predictors 39 have shown excellent, 47 good, 33 marginal, and 28 poor ability to classify binders from non-binders. The classifiers for HLA-A*0201, A*0301, A*1101, B*0702, B*0801, and B*1501 have excellent, and for A*2402 moderate classification accuracy. Sixteen prediction servers predict peptide binding affinity to MHC-I molecules with high accuracy; correlation coefficients ranging from r = 0.55 (B* 0801) to r = 0.87 (A*0201). Conclusion: Non-linear predictors outperform matrix-based predictors. Most predictors can be improved by non-linear transformations of their raw prediction scores. The best predictors of peptide binding are also best in prediction of T-cell epitopes. We propose a new standard for MHC-I binding prediction - a common scale for normalization of prediction scores, applicable to both experimental and predicted data. The results of this study provide assistance to researchers in selection of most adequate prediction tools and selection criteria that suit the needs of their projects. C1 [Lin, Hong Huang; Tongchusak, Songsak; Reinherz, Ellis L.; Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Ray, Surajit] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld, Australia. RP Brusic, V (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM Honghuang_Lin@dfci.harvard.edu; Sray@math.bu.edu; Songsak_Tongchusak@dfci.harvard.edu; Ellis_Reinherz@dfci.harvard.edu; Vladimir_Brusic@dfci.harvard.edu OI Lin, Honghuang/0000-0003-3043-3942 FU PHS HHS [U19 A157330] NR 66 TC 127 Z9 127 U1 0 U2 11 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 MAR 16 PY 2008 VL 9 AR 8 DI 10.1186/1471-2172-9 PG 13 WC Immunology SC Immunology GA 297ZW UT WOS:000255656900001 PM 18366636 ER PT J AU Pisegna, JR Sostek, MB Monyak, JT Miner, PB AF Pisegna, J. R. Sostek, M. B. Monyak, J. T. Miner, P. B., Jr. TI Intravenous esomeprazole 40 mg vs. intravenous lansoprazole 30 mg for controlling intragastric acidity in healthy adults SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; SUPPRESSION; PANTOPRAZOLE; RABEPRAZOLE; SECRETION; PH AB Background Intravenous (IV) formulations of proton pump inhibitors are effective for patients in whom oral therapy is not appropriate. Aim To compare IV esomeprazole and W lansoprazole for the control of intragastric pH. Methods In this open-label crossover study, healthy, Helicobacter pylori-negative adults were randomized to one of two treatment sequences, each consisting of two 5-day dosing periods of TV esomeprazole 40 mg or IV lansoprazole 30 mg. Twenty- four-hour intragastric pH monitoring was conducted on days 1 and 5 of each dosing period. Results On days 1 and 5, intragastric pH was >4.0 significantly longer with esomeprazole than lansoprazole (least-squares means: day 1, 40.0% vs. 33.6%; day 5, 61.9% vs. 45.4%; both P < 0.0001). During the first 4 h of pH monitoring, intragastric pH was >4.0 significantly longer on days 1 and 5 with esomeprazole than lansoprazole (P < 0.0001). Kaplan-Meier estimates of median hours to stable pH >4.0 were 4.92 for esomeprazole and 5.75 for lansoprazole (P = 0.0014 for test on Gehan scores). Conclusion In healthy adults, IV esomeprazole 40 ing controlled intragastric acidity faster and more effectively than W lansoprazole 30 mg. C1 [Pisegna, J. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Pisegna, J. R.] VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA 90095 USA. [Sostek, M. B.; Monyak, J. T.] AstraZeneca LP, Wilmington, DE USA. [Miner, P. B., Jr.] Oklahoma Fdn Digest Res, Oklahoma City, OK USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, Vet Adm Med Ctr W, Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 315, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu FU NCRR NIH HHS [M01-RR00865] NR 15 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD MAR 15 PY 2008 VL 27 IS 6 BP 483 EP 490 DI 10.1111/j.1365-2036.2007.03592.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 278OG UT WOS:000254295600004 PM 18162083 ER PT J AU Di Carlo, D Edd, JF Irimia, D Tompkins, RG Toner, M AF Di Carlo, Dino Edd, Jon F. Irimia, Daniel Tompkins, Ronald G. Toner, Mehmet TI Equilibrium separation and filtration of particles using differential inertial focusing SO ANALYTICAL CHEMISTRY LA English DT Article ID FIELD-FLOW FRACTIONATION; SPLITT FRACTIONATION; POISEUILLE FLOW; BLOOD-CELLS; DIELECTROPHORESIS; CHROMATOGRAPHY; TRANSPORT; FLUID; CHIP AB Rapid separation and filtration of particles in solution has a wide range of applications including blood cell separation, ultrasound contrast agent preparation, and purification of fermentation products. However, current techniques that provide quick processing rates are high in complexity. We present a rapid microfluidic filtration technology capable of separating particles based on size, with purities from 90 to 100% and high-volume throughputs of 1 mL/min. Data for separation of rigid particles, deformable emulsions, and platelets from whole blood are presented. The system is based upon differential inertial focusing of particles of varying sizes and allows continuous separation based only on intrinsic hydrodynamic forces developed in a flow through an asymmetrically curved channel. A theoretical description of the underlying forces is developed, and in combination with data determining a size cutoff for separation, a semiempirical relationship describing how channel geometry is related to this cutoff is shown. Cascading separations in series is shown to be useful for increasing purity and yield. This type of microfluidic system can filter deformable particles, is largely independent of particle density, and can provide throughputs typical of macroscale filtration in a compact format, enabling applications in blood filtration and particle concentration. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Hosp Children, BioMEMS Resource Ctr Ctr Engn Med & Srug Serv, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, BioMEMS Resource Ctr Ctr Engn Med & Srug Serv, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503] NR 29 TC 178 Z9 178 U1 7 U2 102 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 2008 VL 80 IS 6 BP 2204 EP 2211 DI 10.1021/ac702283m PG 8 WC Chemistry, Analytical SC Chemistry GA 274QX UT WOS:000254017000048 PM 18275222 ER PT J AU Driver, CB Wallace, DJ Lee, JC Forbess, CJ Pourrabbani, S Minoshima, S Waxman, AD Weisman, MH AF Driver, Catherine B. Wallace, Daniel J. Lee, Jessica C. Forbess, Chelsey J. Pourrabbani, Shahram Minoshima, Satoshi Waxman, Alan D. Weisman, Michael H. TI Clinical validation of the watershed sign as a marker for neuropsychiatric systemic lupus erythematosus SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; INVOLVEMENT; PREVALENCE AB Objective. To study the relationship between single-photon-emission computed tomography (SPECT) brain imaging and neuropsychiatric signs/symptoms in a cohort of patients with systemic lupus erythematosus (SLE), analyzed using a stereotactic surface projection (SSP) technique. Methods. Thirty-seven SLE patients were referred for Tc-99m-ethyl cysteinate dimer SPECT brain imaging because of neuropsychiatric signs/symptoms. Nineteen normal controls were studied with the identical protocol. Reconstructed images were computed and Z scores were calculated using the SSP technique with the 2-sample t-tests comparing normal controls with SLE patients, and patients with mild cognitive dysfunction with those with severe cognitive dysfunction. The clinical characteristics of SLE patients were collected by retrospective chart review and categorized according to American College of Rheumatology case definitions for neuropsychiatric SLE. Cognitive dysfunction was rated by the treating physician on a scale of 0-3. Results. Thirty of 37 SLE patients had abnormal SPECT results. SLE patients had reduced perfusion in the watershed areas of the frontal lobes bilaterally compared with controls. Additionally, SLE patients with severe cognitive dysfunction had more severe perfusion deficits than those with mild cognitive dysfunction. In some patients with severe cognitive dysfunction, the watershed areas had Z scores >= 4 SDs below controls. Conclusion. A convenience sample of patients with SLE and neuropsychiatric signs/symptoms demonstrated reduced perfusion in the watershed areas of the frontal lobes on SPECT scanning analyzed by the SSP technique. The severity of findings correlated with severity of cognitive dysfunction. The area of the brain affected is one that is susceptible to ischemia. C1 [Driver, Catherine B.; Wallace, Daniel J.; Lee, Jessica C.; Forbess, Chelsey J.; Waxman, Alan D.; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Pourrabbani, Shahram] W Los Angeles VA Hosp, Los Angeles, CA USA. [Minoshima, Satoshi] Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Weisman, MH (reprint author), 8700 Beverly Blvd,Becker B-131, Los Angeles, CA 90048 USA. EM michael.weisman@cshs.org NR 21 TC 14 Z9 14 U1 0 U2 0 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 MAR 15 PY 2008 VL 59 IS 3 BP 332 EP 337 DI 10.1002/art.23308 PG 6 WC Rheumatology SC Rheumatology GA 272IA UT WOS:000253851900006 PM 18311758 ER PT J AU Krathen, MS Dunham, J Gaines, E Junkins-Hopkins, J Kim, E Kolasinski, SL Kovarik, C Kwan-Morley, J Okawa, J Propert, K Rogers, N Rose, M Thomas, P Troxel, AB Van Voorhees, A Von Feldt, J Weber, AL Werth, VP AF Krathen, M. S. Dunham, J. Gaines, E. Junkins-Hopkins, J. Kim, E. Kolasinski, S. L. Kovarik, C. Kwan-Morley, J. Okawa, J. Propert, K. Rogers, N. Rose, M. Thomas, P. Troxel, A. B. Van Voorhees, A. Von Feldt, J. Weber, A. L. Werth, V. P. TI The Cutaneous Lupus Erythematosus Disease Activity and Severity Index: Expansion for rheumatology and dermatology SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol ID MANIFESTATIONS AB Objective. To evaluate the validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for use by rheumatologists via reliability testing, and to extend the validation for dermatologists. Methods. Fourteen subjects with cutaneous lupus erythematosus (CLE; n = 10), a mimicker skin disease only (a cutaneous lesion that may appear clinically similar to CLE; n = 1), or both (n = 3) were rated with the CLASI by academic-based dermatologists (n = 5) and rheumatologists (n = 5). Results. The dermatology intraclass correlation coefficient (ICC) was 0.92 for activity and 0.82 for damage; for rheumatology the ICC was 0.83 for activity and 0.86 for damage. For intrarater reliability, the dermatology Spearman's rho was 0.94 for activity and 0.97 for damage; for rheumatology the Spearman's rho was 0.91 for activity and 0.99 for damage. Conclusion. Our data confirm the reliability of the CLASI when used by dermatologists and support the CLASI as a reliable instrument for use by rheumatologists. C1 [Krathen, M. S.; Dunham, J.; Gaines, E.; Junkins-Hopkins, J.; Kim, E.; Kolasinski, S. L.; Kovarik, C.; Kwan-Morley, J.; Okawa, J.; Rose, M.; Thomas, P.; Van Voorhees, A.; Von Feldt, J.; Werth, V. P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19119 USA. [Propert, K.; Troxel, A. B.; Weber, A. L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rogers, N.] Tulane Univ, Sch Med, New Orleans, LA 70118 USA. [Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, 2 Rhoads Pavilion,3600 Spruce St, Philadelphia, PA 19119 USA. EM werth@mail.med.upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU NIAMS NIH HHS [K24 AR002207] NR 10 TC 28 Z9 30 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 MAR 15 PY 2008 VL 59 IS 3 BP 338 EP 344 DI 10.1002/art.23319 PG 7 WC Rheumatology SC Rheumatology GA 272IA UT WOS:000253851900007 PM 18311759 ER PT J AU Kasai, K Yamasue, H Gilbertson, MW Shenton, ME Rauch, SL Pitman, RK AF Kasai, Kiyoto Yamasue, Hidenori Gilbertson, Mark W. Shenton, Martha E. Rauch, Scott L. Pitman, Roger K. TI Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anterior cingulate gyrus; brain; magnetic resonance imaging; monozygotic twins; posttraumatic stress disorder ID MEDIAL PREFRONTAL CORTEX; VOXEL-BASED ANALYSIS; HIPPOCAMPAL VOLUME; HUMAN BRAIN; EXPOSURE; PTSD; MRI; SCHIZOPHRENIA; MORPHOMETRY; EXTINCTION AB Background: Controversy exists over the nature and origin of reduced regional brain volumes in posttraumatic stress disorder (PTSD). At issue is whether these reductions represent preexisting vulnerability factors for developing PTSD upon traumatic exposure or acquired PTSD signs due to the traumatic stress that caused the PTSD or the chronic stress of having the disorder (or both). We employed a case-control design in monozygotic twin pairs discordant for combat exposure to address the preexisting versus acquired origin of brain morphometric abnormalities in PTSD. Methods: We used voxel-based morphometry to search for gray matter density reductions in magnetic resonance imaging (MRI) data obtained in a previous study of combat-exposed Vietnam veteran twins with (n = 18) versus without (n = 23) PTSD and their "high-risk" versus "low-risk" (respectively) identical combat-unexposed cotwins. Results: Compared with the combat-exposed twins without PTSD, the combat-exposed twins with PTSD showed significant gray matter density reductions in four predicted brain regions: right hippocampus, pregenual anterior cingulate cortex (ACC), and left and right insulae. There was a significant PTSD Diagnosis X Combat Exposure interaction in pregenual ACC in which combat-exposed PTSD twins had lower gray matter density than their own combat-unexposed cotwins as well as than the combat-exposed twins without PTSD and their cotwins. Conclusions: The results point to gray matter volume diminutions in limbic and paralimbic structures in PTSD. The pattern of results obtained for pregenual ACC suggests that gray matter reduction in this region represents an acquired sign of PTSD consistent with stress-induced loss. C1 [Kasai, Kiyoto; Yamasue, Hidenori] Univ Tokyo, Dept Neuropsychiat, Grad Sch Med, Tokyo, Japan. [Gilbertson, Mark W.] VA Med Ctr, Res Serv, Manchester, NH USA. [Shenton, Martha E.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Surg Planning Lab, MRI Div, Dept Radiol, Boston, MA 02115 USA. [Rauch, Scott L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Gilbertson, Mark W.; Shenton, Martha E.; Rauch, Scott L.; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Room 2616,Bldg 149,13th St, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu FU NIMH NIH HHS [K05MH01110, R01 MH054636, R01 MH054636-09, R01MH54636] NR 50 TC 154 Z9 156 U1 2 U2 13 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 MAR 15 PY 2008 VL 63 IS 6 BP 550 EP 556 DI 10.1016/j.biopsych.2007.06.022 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 268ZD UT WOS:000253618300004 PM 17825801 ER PT J AU Taylor, FB Martin, P Thompson, C Williams, J Mellman, TA Gross, C Peskind, ER Raskind, MA AF Taylor, Fletcher B. Martin, Patti Thompson, Charles Williams, Judi Mellman, Thomas A. Gross, Christopher Peskind, Elaine R. Raskind, Murray A. TI Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: A placebo-controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE nightmare; posttraumatic stress disorder; prazosin; rapid eye movement sleep; sleep disturbance ID COMBAT-RELATED PTSD; REM-SLEEP; PHARMACOTHERAPY; NIGHTMARES; VETERANS; METHOXAMINE; DISTURBANCE; ANTAGONISTS; TEGMENTUM; EFFICACY AB Background: Prazosin, a central nervous system (CNS) active alpha-1 adrenoreceptor antagonist, has reduced nightmares and sleep disturbance in placebo-controlled studies of combat-related posttraumatic stress disorder (PTSD). We evaluated objective sleep parameters and PTSD symptoms in a placebo-controlled prazosin trial for civilian trauma-related PTSD. Methods: Thirteen outpatients with chronic civilian trauma PTSD, frequent nightmares, and sleep disturbance participated in a randomized placebo-controlled crossover trial of prazosin. Sleep parameters were quantified at home with the REMView (Respironics, Pittsburgh, Pennsylvania). The PTSD symptoms were quantified with the Clinician Administered PTSD Scale (CAPS) "recurrent distressing dreams" and "disturbed sleep" items, a non-nightmare distressed awakenings scale, the PTSD Dream Rating Scale (PDRS), the PTSD Checklist-Civilian (PCL-C), and the Clinical Global Impression of Improvement (CGI-1). Results: Prazosin compared with placebo significantly increased total sleep time by 94 min; increased rapid eye movement (REM) sleep time and mean REM period duration without altering sleep onset latency; significantly reduced trauma-related nightmares, distressed awakenings, and total PCL scores; significantly improved CGI-I scores; and changed PDRS scores toward normal dreaming. Conclusions: Prazosin reductions of nighttime PTSD symptoms in civilian trauma PTSD are accompanied by increased total sleep time, REM sleep time, and mean REM period duration in the absence of a sedative-like effect on sleep onset latency. C1 [Taylor, Fletcher B.; Gross, Christopher; Peskind, Elaine R.; Raskind, Murray A.] VA Puget Sound Hlth Care Syst, NW Network VISN Mental Illness Res Educ & Clin Ct, Seattle, WA 98108 USA. [Thompson, Charles; Gross, Christopher; Peskind, Elaine R.; Raskind, Murray A.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. [Taylor, Fletcher B.; Martin, Patti; Williams, Judi] Rainier Associates, Tacoma, WA USA. [Taylor, Fletcher B.; Thompson, Charles; Gross, Christopher; Peskind, Elaine R.; Raskind, Murray A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Mellman, Thomas A.] Howard Univ, Washington, DC 20059 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, NW Network VISN Mental Illness Res Educ & Clin Ct, 1660 S Columbian Way,S-116, Seattle, WA 98108 USA. EM murray.raskind@va.gov FU NIMH NIH HHS [R01 MH069867, MH069867, R01 MH069867-03] NR 32 TC 132 Z9 137 U1 3 U2 10 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 MAR 15 PY 2008 VL 63 IS 6 BP 629 EP 632 DI 10.1016/j.biopsych.2007.07.001 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 268ZD UT WOS:000253618300014 PM 17868655 ER PT J AU Saffarian, S Kirchhausen, T AF Saffarian, Saveez Kirchhausen, Tomas TI Differential evanescence nanometry: Live-cell fluorescence measurements with 10-nm axial resolution on the plasma membrane SO BIOPHYSICAL JOURNAL LA English DT Article ID CLATHRIN-COATED PITS; INTERNAL-REFLECTION FLUORESCENCE; MICROSCOPY; ACTIN; RECRUITMENT; DYNAMICS; INVAGINATION; ENDOCYTOSIS; MOVEMENTS; PROTEINS AB We present a method to resolve components within a diffraction-limited object by tracking simultaneously the average axial positions of two different sets of fluorescent molecules within it. The axial positions are then subtracted from each other to determine the separation of the two sets of fluorophores. This method follows the dynamic changes in the separation of the two sets of fluorophores with freely rotating dipoles using sequential acquisitions with total internal reflection and wide-field illumination, and it can be used to measure the formation of small structures on living cells. We have verified that we can achieve a resolution of 10 nm, and we have used the method to follow the location of clathrin and its adaptor AP-2 as they are recruited to a diffraction-limited coated pit during its assembly at the plasma membrane. We find a gradually increasing axial separation between the centroids of clathrin and AP-2 distribution, up to a final value of 30 nm just before coated-pit pinching and formation of the coated vesicle. C1 [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM Kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [GM 075252, GM 62566, P01 GM062566, R01 GM075252] NR 43 TC 61 Z9 61 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR 15 PY 2008 VL 94 IS 6 BP 2333 EP 2342 DI 10.1529/biophysj.107.117234 PG 10 WC Biophysics SC Biophysics GA 269UQ UT WOS:000253676200036 PM 17993495 ER PT J AU Marango, J Shimoyama, M Nishio, H Meyer, JA Min, DJ Sirulnik, A Martinez-Martinez, Y Chesi, M Bergsagel, PL Zhou, MM Waxman, S Leibovitch, BA Walsh, MJ Licht, JD AF Marango, Jotin Shimoyama, Manabu Nishio, Hitomi Meyer, Julia A. Min, Dong-Joon Sirulnik, Andres Martinez-Martinez, Yolanda Chesi, Marta Bergsagel, P. Leif Zhou, Ming-Ming Waxman, Samuel Leibovitch, Boris A. Walsh, Martin J. Licht, Jonathan D. TI The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor SO BLOOD LA English DT Article ID DOMAIN-CONTAINING GENE; MULTIPLE-MYELOMA; SET DOMAIN; T(4/14) TRANSLOCATION; FGFR3 EXPRESSION; MAMMALIAN-CELLS; PWWP DOMAIN; CANCER; H3; TRIMETHYLATION AB MMSET, identified by its fusion to the IgH locus in t(4;14)-associated multiple myeloma, possesses domains found within chromatin regulators, including the SET domain. MMSET protein is overexpressed and highly associated with chromatin in myeloma cell lines carrying t(4;14). MMSET possesses methyltransferase activity for core histone H3 lysine 4 and histone 4 lysine 20, whereas MMSET made in cells only modified H4. Segments of MMSET fused to the Gal4 DNA binding domain repressed transcription of a chromatin-embedded Gal4 reporter gene. MMSET-mediated repression was associated with increased H4K20 methylation gene and loss of histone acetylartion. Consistent with this repressive activity, MMSET could form a complex with HDAC1 and HDAC2, mSin3a, and the histone demethylase LSD1, suggesting that it is a component of corepressor complexes. Furthermore, MMSET coexpression enhances HDAC1- and HDAC2-mediated repression in transcriptional reporter assays. Finally, shRNA-mediated knockdown of MMSET compromised viability of a myeloma cell line, suggesting a biologic role for the protein in malignant cell growth. Collectively, these data suggest that, by acting directly as a modifier of chromatin as well as through binding of other chromatin-modifying enzymes, MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma. C1 [Meyer, Julia A.; Min, Dong-Joon; Licht, Jonathan D.] Northwestern Univ, Robert Lurie Comprehens Canc Ctr, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA. [Nishio, Hitomi; Walsh, Martin J.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Shimoyama, Manabu] Kobe Univ, Grad Sch Med, Div Hematol Oncol, Kobe, Hyogo, Japan. [Sirulnik, Andres] Dana Farber Canc Inst, Div Hematol Malignancy, Boston, MA 02115 USA. [Chesi, Marta; Bergsagel, P. Leif] Mayo Clin, Scottsdale, AZ USA. [Zhou, Ming-Ming] Mt Sinai Sch Med, Struct Biol Program, New York, NY USA. RP Walsh, MJ (reprint author), Northwestern Univ, Robert Lurie Comprehens Canc Ctr, Feinberg Sch Med, Div Hematol & Oncol, 303 E Superior St,Lurie 5-123, Chicago, IL 60611 USA. EM j-licht@northwestern.edu RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [P50 CA100707-060008, P50 CA100707]; NIA NIH HHS [R01 AG020686, R01 AG020686-05] NR 45 TC 108 Z9 110 U1 1 U2 6 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 MAR 15 PY 2008 VL 111 IS 6 BP 3145 EP 3154 DI 10.1182/blood-2007-06-092122 PG 10 WC Hematology SC Hematology GA 274OC UT WOS:000254009600029 PM 18156491 ER PT J AU Minamishima, YA Moslehi, J Bardeesy, N Cullen, D Bronson, RT Kaelin, WG AF Minamishima, Yoji Andrew Moslehi, Javid Bardeesy, Nabeel Cullen, Darragh Bronson, Roderick T. Kaelin, William G., Jr. TI Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure SO BLOOD LA English DT Article ID HYPOXIA-INDUCIBLE-FACTOR; CHRONIC KIDNEY-DISEASE; FACTOR-I; VASCULAR TUMORS; CEREBRAL-ISCHEMIA; DOMAIN PROTEIN-2; FACTOR-ALPHA; MOUSE MODEL; OXYGEN; HIF AB Pharmacologic activation of the heterodimeric HIF transcription factor appears promising as a strategy to treat diseases, such as anemia, myocardial infarction, and stroke, in which tissue hypoxia is a prominent feature. HIF accumulation is normally linked to oxygen availability because an oxygen-dependent posttranslational modification (prolyl hydroxylation) marks the HIF alpha subunit for polyubiquitination and destruction. Three enzymes (PHD1, PHD2, and PHD3) capable of catalyzing this reaction have been identified, although PHD2 (also called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture experiments. We found that conditional inactivation of PHD2 in mice is sufficient to activate a subset of HIF target genes, including erythropoietin, leading to striking increases in red blood cell production. Mice lacking PHD2 exhibit premature mortality associated with marked venous congestion and dilated cardiomyopathy. The latter is likely the result of hyperviscosity syndrome and volume overload, although a direct effect of chronic, high-level HIF stimulation on cardiac myocytes cannot be excluded. C1 [Minamishima, Yoji Andrew; Moslehi, Javid; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Minamishima, Yoji Andrew; Moslehi, Javid; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Moslehi, Javid; Cullen, Darragh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Minamishima, Yoji/E-5380-2010 OI Minamishima, Yoji/0000-0001-7995-9318 FU Howard Hughes Medical Institute; NHLBI NIH HHS [K12 HL083786] NR 49 TC 154 Z9 162 U1 0 U2 5 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 MAR 15 PY 2008 VL 111 IS 6 BP 3236 EP 3244 DI 10.1182/blood-2007-10-1178,12 PG 9 WC Hematology SC Hematology GA 274OC UT WOS:000254009600040 PM 18096761 ER PT J AU Bass, AJ Meyerhardt, JA Chan, JA Giovannucci, EL Fuchs, CS AF Bass, Adam J. Meyerhardt, Jeffrey A. Chan, Jennifer A. Giovannucci, Edward L. Fuchs, Charles S. TI Family history and survival after colorectal cancer diagnosis SO CANCER LA English DT Article DE colorectal cancer; family history; survival; cohort study; epidemiology ID ISLAND METHYLATOR PHENOTYPE; NATIONAL DEATH INDEX; COLON-CANCER; MICROSATELLITE-INSTABILITY; RISK; PREDICTOR; BENEFIT AB BACKGROUND. A history of colorectal cancer in a first-degree relative is a recognized risk factor for developing this malignancy. The influence of a family history of colorectal cancer on survival after a diagnosis of colorectal cancer was examined in a large cohort of women. METHODS. We analyzed data from 1001 women diagnosed with colorectal cancer while participating in a prospective cohort study. Data on family history were obtained before cancer diagnosis. We computed Cox proportional hazards for cancer-specific and overall mortality according to a family history of colorectal cancer, adjusting for other predictors for survival. RESULTS. Before diagnosis, 16% of colorectal patients reported a history of colorectal cancer in a first-degree relative. Patients with a history of colorectal cancer in 1 or more first-degree relatives experienced an adjusted hazard ratio (HR) for overall mortality of 1.32 (95% confidence interval [CI], 1.01-1.72) and colorectal cancer-specific mortality of 1.38 (95% CI, 1.02-1.86) when compared with those without a family history. Moreover, patients with 2 or more affected relatives had an HR for overall mortality of 2.07 (95% CI, 1.14-3.76) and cancer-specific mortality of 2.19 (95% CI, 1.10-4.38). The significant deleterious effect of family history was limited to patients with advanced disease at presentation and cancers originating in the colon. CONCLUSIONS. Among women with colorectal cancer, a history of colorectal cancer in a first-degree relative was associated with a significant decrease in survival. Additional study is needed to validate these findings and determine whether specific germline polymorphisms correlate with clinical outcomes. Cancer C1 [Bass, Adam J.; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Fuchs, Charles S.] Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ajbass@partners.org FU NCI NIH HHS [P01 CA087969, P01CA087969] NR 22 TC 18 Z9 18 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2008 VL 112 IS 6 BP 1222 EP 1229 DI 10.1002/cncr.23294 PG 8 WC Oncology SC Oncology GA 274QP UT WOS:000254016200005 PM 18219663 ER PT J AU Farmer, MM Bastani, R Kwan, L Belman, M Ganz, PA AF Farmer, Melissa M. Bastani, Roshan Kwan, Lorna Belman, Michael Ganz, Patricia A. TI Predictors of colorectal cancer screening from patients enrolled in a managed care health plan SO CANCER LA English DT Article DE patient survey; colorectal cancer screening; provider influence; patient barriers; managed care ID UNITED-STATES; GUIDELINES; TRIAL; WOMEN; RECOMMENDATIONS; PREVENTION; PHYSICIANS; BEHAVIOR; BARRIERS; PROGRESS AB BACKGROUND. Despite the growing recognition of the importance of colorectal cancer (CRC) screening in reducing cancer mortality, national screening rates are low, indicating a critical need to understand the barriers and remedies for underutilization of CRC screening tests. METHODS. Using results from independent cross-sectional telephone surveys with patients aged >= 50 years performed before (2000; n = 498) and after (2003; n = 482) a quality improvement intervention for CRC screening within a large managed care health plan, the trends and predictors of CRC screening with fecal occult blood test (FOBT) and/or endoscopy (flexible sigmoidoscopy/colonoscopy) were examined from a patient perspective. RESULTS. In 2000, patient reported screening rates within guidelines were 38% for any test, 23% for endoscopy, and 22% for FOBT. In 2003, screening rates increased to 50% for any test, 39% for endoscopy, and 24% for FOBT. Having discussed CRC with a doctor significantly increased the odds of being screened (FOBT: odds ratio [OR], 2.09 [95% confidence interval (95% CI), 1.47-2.96]; endoscopy: OR, 2.33 [95% CI, 1.67-3.26]; and any test: OR, 2.86 [95% CI, 2.06-3.961]), and reporting barriers to CRC in general decreased the odds of being screened (FOBT: OR, 0.76 [95% CI, 0.60-0.95]; endoscopy: OR, 0.74 [95% CI, 0.60-0.92]; and any test: OR, 0.66 [95% CI, 0.54-0.80]). CONCLUSIONS. Although screening rates increased over the 3-year period, evidence was found of ongoing underutilization of CRC screening. The 2 strongest determinants of obtaining CRC screening were provider influence and patient barriers related to CRC screening in general, pointing to the need for multilevel interventions that target both the provider and patient. C1 [Farmer, Melissa M.] Ctr Excellence Study Hlthcare Provider Behav, Greater Los Angeles Hlth Serv Res, Sepulveda, CA USA. [Farmer, Melissa M.] Ctr Excellence Study Hlthcare Provider Behav, Greater Los Angeles Hlth Serv Dev, Sepulveda, CA USA. [Farmer, Melissa M.; Bastani, Roshan; Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Bastani, Roshan; Kwan, Lorna; Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Belman, Michael] Blue Cross Calif, Clin Qual, Woodland Hills, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Farmer, MM (reprint author), Vet Affairs GLA Hlthcare Syst, 16111 Plummer St, Sepulveda, CA 91343 USA. EM Melissa.Farmer@va.gov FU NCI NIH HHS [R01 CA75544] NR 26 TC 22 Z9 23 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2008 VL 112 IS 6 BP 1230 EP 1238 DI 10.1002/cncr.23290 PG 9 WC Oncology SC Oncology GA 274QP UT WOS:000254016200006 PM 18266204 ER PT J AU Ross, RW Xie, WL Regan, MM Pomerantz, M Nakabayashi, M Daskivich, TJ Sartor, O Taplin, ME Kantoff, PW Oh, WK AF Ross, Robert W. Xie, Wanling Regan, Meredith M. Pomerantz, Mark Nakabayashi, Mari Daskivich, Timothy J. Sartor, Oliver Taplin, Mary-Ellen Kantoff, Philip W. Oh, William K. TI Efficacy of androgen deprivation therapy (ADT) in patients with advanced prostate SO CANCER LA English DT Article DE prostate cancer; androgen deprivation therapy; metastatic disease; prognosis ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; NATURAL-HISTORY; HORMONAL-THERAPY; LOCAL TREATMENT; ANTIGEN; IMMEDIATE; MEN; PROGRESSION; RADIATION AB BACKGROUND. The purpose of this study was to compare predictive factors for the efficacy of androgen deprivation therapy (ADT) in men with hormone-sensitive prostate cancer (HSPC) either with (M+) or without (M-) metastases. METHODS. A cohort of prostate cancer patients was identified from a medical oncology practice treated with ADT for presumed nonlocalized prostate cancer, evaluated the efficacy of ADT using prostate-specific antigen (PSA) time to progression (TTP) and compared factors associated with TTP in M- and M+ patients. RESULTS. In this 553 patient cohort 51% were M- and 49% M+. The median TTP on ADT for the M- group was 33.2 months, versus 15.9 months in the M+ group (P <.0001). In multivariate analyses, lower biopsy Gleason score (GS), the absence of metastases, and lower serum PSA at ADT initiation all were associated with the efficacy of ADT The association between GS and TTP was confined to M+ patients, whereas the association between PSA at ADT initiation and TTP was confined to M- patients. Use of ADT as part of local treatment was associated with a shortened TTP in both groups (hazard ratio [HR], 1.45, 95% confidence interval [CI], 1.10-1.91). CONCLUSIONS. In this large, retrospective study of HSPC patients in a medical oncology practice treated with ADT for nonlocalized prostate cancer, we found factors predicting efficacy of this treatment differed based on whether metastases were present at ADT initiation. The use of ADT as a part of local therapy was associated with a significantly decreased TTP, regardless of metastatic disease status. C1 [Ross, Robert W.; Xie, Wanling; Regan, Meredith M.; Pomerantz, Mark; Nakabayashi, Mari; Daskivich, Timothy J.; Sartor, Oliver; Taplin, Mary-Ellen; Kantoff, Philip W.; Oh, William K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ross, RW (reprint author), Dana 1230,44 Binney St, Boston, MA 02115 USA. EM Robert_ross@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [5P50CA90381] NR 19 TC 53 Z9 53 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2008 VL 112 IS 6 BP 1247 EP 1253 DI 10.1002/cncr.23304 PG 7 WC Oncology SC Oncology GA 274QP UT WOS:000254016200008 PM 18293426 ER PT J AU Zhang, GQ Njaw, CN Park, JM Naruse, C Asano, M Tsao, HS AF Zhang, Guoqi Njaw, Ching-Ni Park, Jong Min Naruse, Chie Asano, Masahide Tsao, Hensin TI EphA2 is an essential mediator of UV radiation-induced apoptosis SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; TYROSINE KINASE; UP-REGULATION; IN-VIVO; MELANOMA PROGRESSION; OVARIAN-CANCER; SKIN-CANCER; EXPRESSION; RECEPTOR; OVEREXPRESSION AB One of the physiologic consequences of excessive UV radiation (UVR) exposure is apoptosis. This critical response serves to eliminate genetically injured cells and arises, in part, from activation of DNA damage and p53 signaling. Other contributory pathways, however, likely exist but have not been fully characterized. In a recent global screen of UVR response genes in melanocytes, we identified the receptor tyrosine kinase EPHA2. Using a combination of genetic and pharmacologic approaches, we set out to investigate the upstream regulation of EphA2 by UVR and the functional consequences of this effect. We found that the UVR-associated increase in EphA2 occurs in melanocytes, keratinocytes, and fibroblasts from both human and murine sources. More specifically, UVR effectively up-regulated EphA2 individually in p53-null, p63-null, and p73-null murine embryonic fibroblasts (MEF), suggesting that the p53 family of transcription factors is not essential for the observed effect. However, inhibition of mitogen-activated protein kinase (MAPK) signaling by U0126 and PD98059 significantly reduced the UVR response whereas overexpression of oncogenic AWAS led to an increase in EphA2. These results confirm that UVR induces EphA2 by a p53-independent, but MAPK-dependent, mechanism. In response to IN irradiation, Epha2(-/-) MEFs were highly resistant to UTR-mediated cytotoxicity and apoptosis whereas introduction of EphA2 into both wild-type and p53-null MEFs led to activation of an apoptotic program that can be blocked by caspase-8 inhibition. These functional findings suggest that EphA2 is in fact an essential p53-independent, caspase-8-dependent proapoptotic factor induced by UVR. C1 [Zhang, Guoqi; Njaw, Ching-Ni; Park, Jong Min; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Guoqi; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, MGH Canc Ctr, Boston, MA 02114 USA. [Naruse, Chie; Asano, Masahide] Kanazawa Univ, Adv Sci Res Ctr, Div Transgen Anim Sci, Kanazawa, Ishikawa 920, Japan. RP Tsao, HS (reprint author), Massachusetts Gen Hosp, Dept Dermatol, MGH Canc Ctr, Barlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@patners.org RI Njauw, Ching-Ni/H-8046-2012 FU NIEHS NIH HHS [R21 ES013964] NR 30 TC 28 Z9 33 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 MAR 15 PY 2008 VL 68 IS 6 BP 1691 EP 1696 DI 10.1158/0008-5472.CAN-07-2372 PG 6 WC Oncology SC Oncology GA 274TO UT WOS:000254024400012 PM 18339848 ER PT J AU Cheng, ASL Culhane, AC Chan, MWY Venkataranm, CR Ehrich, M Nasir, A Rodriguez, BAT Liu, J Yan, PS Quackenbush, J Nephew, KP Yeatman, TJ Huang, THM AF Cheng, Alfred S. L. Culhane, Aedin C. Chan, Michael W. Y. Venkataranm, Chinnambally R. Ehrich, Mathias Nasir, Aejaz Rodriguez, Benjamin A. T. Liu, Joseph Yan, Pearlly S. Quackenbush, John Nephew, Kenneth P. Yeatman, Timothy J. Huang, Tim H-M. TI Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR ACTIVITY; DNA METHYLATION; RECEPTOR-ALPHA; STEM-CELLS; HYPERMETHYLATION; CARCINOGENESIS; MECHANISMS; REVEALS; DISEASE; GROWTH AB Estrogen imprinting is used to describe a phenomenon in which early developmental exposure to endocrine disruptors increases breast cancer risk later in adult life. We propose that long-lived, self-regenerating stem and progenitor cells are more susceptible to the exposure injury than terminally differentiated epithelial cells in the breast duct. Mammospheres, containing enriched breast progenitors, were used as an exposure system to simulate this imprinting phenomenon in vitro. Using MeDIP-chip, a methylation microarray screening method, we found that 0.5% (120 loci) of human CpG islands were hypermethylated in epithelial cells derived from estrogen-exposed progenitors compared with the non-estrogen-exposed control cells. This epigenetic event may lead to progressive silencing of tumor suppressor genes, including RUNX3, in these epithelial cells, which also occurred in primary breast tumors. Furthermore, normal tissue in close proximity to the tumor site also displayed RUNX3 hypermethylation, suggesting that this aberrant event occurs in early breast carcinogenesis. The high prevalence of estrogen-induced epigenetic changes in primary tumors and the surrounding histologically normal tissues provides the first empirical link between estrogen injury of breast stem/progenitor cells and carcinogenesis. This finding also offers a mechanistic explanation as to why a tumor suppressor gene, such as RUNX3, can be heritably silenced by epigenetic mechanisms in breast cancer. C1 [Cheng, Alfred S. L.; Chan, Michael W. Y.; Rodriguez, Benjamin A. T.; Liu, Joseph; Yan, Pearlly S.; Huang, Tim H-M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA. [Culhane, Aedin C.; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Comp Biol, Boston, MA 02115 USA. [Venkataranm, Chinnambally R.; Yeatman, Timothy J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL USA. [Ehrich, Mathias] Sequenom Inc, San Diego, CA USA. [Cheng, Alfred S. L.] Indiana Univ, Sch Med, Bloomington, IN USA. [Cheng, Alfred S. L.] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong Special Adm Reg, Hong Kong, Hong Kong, Peoples R China. RP Huang, THM (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA. EM tim.huang@osumc.edu RI Yan, Pearlly/E-4339-2011; Cheng, Alfred/C-3327-2014; OI Yan, Pearlly/0000-0003-1965-4920; Cheng, Alfred/0000-0003-2345-6951; Chan, Michael/0000-0003-1431-322X FU NCI NIH HHS [U54 CA11300, P30 CA016058, P30 CA16058, R01 CA069065, R01 CA098522, U19 CA148065]; NIEHS NIH HHS [U01 ES015986] NR 30 TC 88 Z9 93 U1 0 U2 5 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 MAR 15 PY 2008 VL 68 IS 6 BP 1786 EP 1796 DI 10.1158/0008-5472.CAN-07-5547 PG 11 WC Oncology SC Oncology GA 274TO UT WOS:000254024400023 PM 18339859 ER PT J AU Bulk, E Hascher, A Liersch, R Mesters, RM Diederichs, S Sargin, B Gerke, V Hotfilder, M Vormoor, J Berdel, WE Serve, H Muller-Tidow, C AF Bulk, Etmar Hascher, Anoe Liersch, Ruediger Mesters, Rolf M. Diederichs, Sven Sargin, Buelent Gerke, Volker Hotfilder, Marc Vormoor, Josef Berdel, Wolfgang E. Serve, Hubert Mueller-Tidow, Carsten TI Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL; S100P; SURVIVAL; EXPRESSION; GENE; CHEMOTHERAPY; INVASION; ACTIVATION; PROGNOSIS; CARCINOMA AB Development of distant metastasis is the major reason for cancer-related deaths worldwide. Adjuvant therapy approaches after local therapies are most effective when specific targets are inhibited. Recently, we identified S100P overexpression as a strong predictor for metastasis development in early-stage non-small cell lung cancer (NSCLC) patients. Here, we show that S100P overexpression increased angiogenesis in and metastasis formation from s.c. xenotransplants of NSCLC cells. Plasmid-derived short hairpin RNAs (shRNA) were developed as specific adjuvant therapy. I.v. injected shRNA against S100P significantly decreased S100P protein expression in xenograft tumors and inhibited tumor angiogenesis in vivo. Metastasis formation 8 weeks after primary tumor resection was significantly reduced. Lung metastases developed in 31% of mice treated with S100P-targeting shRNAs compared with 64% in control shRNA-treated mice (P < 0.05). These findings suggest that RNA interference-based therapy approaches can be highly effective in the adjuvant setting. C1 [Bulk, Etmar; Hascher, Anoe; Liersch, Ruediger; Mesters, Rolf M.; Sargin, Buelent; Berdel, Wolfgang E.; Serve, Hubert; Mueller-Tidow, Carsten] Univ Munster, Dept Med Hematol & Oncol, D-48129 Munster, Germany. [Hotfilder, Marc] Univ Munster, Dept Pediat Hematol & Oncol, D-48129 Munster, Germany. [Gerke, Volker] Univ Munster, Dept Med Biochem, D-48129 Munster, Germany. [Diederichs, Sven] Massachusetts Gen Hosp, Ctr Canc, Harvard Med Sch, Charlestown, MA USA. [Vormoor, Josef] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England. RP Muller-Tidow, C (reprint author), Univ Munster, Dept Med A Hematol & Oncol, Domagkstr 3, D-48129 Munster, Germany. EM muellerc@uni-muenster.de RI Diederichs, Sven/J-6237-2012; Muller-Tidow, Carsten/B-5257-2014; Muller-Tidow, Carsten/L-4062-2015 OI Diederichs, Sven/0000-0001-7901-4752; NR 31 TC 25 Z9 27 U1 1 U2 5 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 MAR 15 PY 2008 VL 68 IS 6 BP 1896 EP 1904 DI 10.1158/0008-5472.CAN-07-2390 PG 9 WC Oncology SC Oncology GA 274TO UT WOS:000254024400035 PM 18339871 ER PT J AU Pronk, CJ Attema, J Rossi, DJ Sigvardsson, M Bryder, D AF Pronk, Cornelis J. Attema, Joanne Rossi, Derrick J. Sigvardsson, Mikael Bryder, David TI Deciphering developmental stages of adult myelopoiesis SO CELL CYCLE LA English DT Article DE hematopoiesis; hematopoietic stem cell; myeloid progenitor; myeloid precursor; lineage potential; lineage commitment; gene expression ID HEMATOPOIETIC STEM-CELLS; MYELOID LINEAGE COMMITMENT; LYMPHOID PROGENITORS; LONG; DIFFERENTIATION; IDENTIFICATION; PU.1; RECONSTITUTION; ENDOGLIN; MARKER AB The ability to subfractionate minor cellular subsets by multi-parameter flow cytometry and to evaluate such cells for functional properties has been used to ascertain lineal relationships and detail developmental hierarchies in the hematopoietic system for more than 20 years. However, steady advances in technology combined with the use of novel cell surface markers continues to redefine the developmental landscape as novel subpopulations are purified and characterized. We recently used such an approach to stage progenitor cell hierarchy involved in myeloid development with the use of two markers, Slamf1 and Endoglin that have recently been shown to be associated with hematopoietic stem cells. Here, we provide additional characterization of these cellular subsets to further refine their developmental potential. Little or no alterations in lineage potential were observed in these subsets when evaluated in a BCL2 transgenic setting or in response to various growth factor combinations, although BCL2 significantly enhanced their in vitro readout. Gene expression patterns of functionally opposing transcription factors that are known to play key roles for the appropriate development into separate myeloid lineages were associated with the functional activity of prospectively isolated subsets. Multiple genes traditionally associated with early lymphopoiesis were observed in early candidate granulocyte/ monocyte, but not early megakaryocytic and/ or erythroid progenitor cells. When functionally evaluated, such early granulocyte/ monocyte precursors displayed a latent lymphoid activity, which was pronounced in subsets bearing high expression of the tyrosine kinase receptor FLT3. C1 [Pronk, Cornelis J.; Attema, Joanne; Bryder, David] Lund Univ, Immunol Sect, Inst Expt Med Sci, S-22184 Lund, Sweden. [Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pathol, Harvard Stem Cell Inst,Immune Dis Inst, Cambridge, MA 02138 USA. [Sigvardsson, Mikael] Lund Univ, Lund Ctr Stem Cell Biol & Cell Therapy, S-22184 Lund, Sweden. RP Bryder, D (reprint author), Lund Univ, Immunol Sect, Inst Expt Med Sci, Tornavagen 10,BMC 113, S-22184 Lund, Sweden. EM david.bryder@med.lu.se OI Sigvardsson, Mikael/0000-0001-8527-7276 NR 37 TC 8 Z9 8 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2008 VL 7 IS 6 BP 706 EP 713 PG 8 WC Cell Biology SC Cell Biology GA 285IV UT WOS:000254771400004 PM 18461720 ER PT J AU Fonseca, C Dranoff, G AF Fonseca, Catia Dranoff, Glenn TI Capitalizing on the immunogenicity of dying tumor cells SO CLINICAL CANCER RESEARCH LA English DT Article ID APOPTOTIC CELLS; T-CELLS; CAENORHABDITIS-ELEGANS; NKG2D RECEPTOR; OVARIAN-CANCER; IMMUNE-SYSTEM; DEATH; ENGULFMENT; EXPRESSION; LIGANDS AB Cancer cell death occurs continually during tumor development and progression, whereas the selective killing of surviving cancer cells remains the primary objective of antineoplastic treatments. Recent insights into the immunologic consequences of cancer cell death have begun to elucidate the ways in which host antitumor immunity is shaped during cancer pathogenesis and then modulated by therapeutic intervention. Dying tumor cells evoke a range of host responses, dependent in part upon the mode of cell death, which may either impede or foster additional immune-mediated cancer destruction. Within the tumor microenvironment, the capture of apoptotic tumor cells by macrophages and dendritic cells may trigger tolerance networks that contribute to immune suppression, whereas the uptake of necrotic cancer cells may engender inflammatory pathways that fuel antitumor cytotoxicity. Milk fat globule epidermal growth factor 8, a phosphatidylserine-binding protein, and MHC class I chain-related protein A, an NKG2D ligand, play key roles in these competing outcomes. A deeper understanding of the mechanisms underlying the immunogenicity of dying cells informs the crafting of strategies that exploit endogenous or treatment-induced cancer cell death as the basis for stimulating sustained host antitumor cytotoxic reactions. C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 50 TC 33 Z9 34 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 MAR 15 PY 2008 VL 14 IS 6 BP 1603 EP 1608 DI 10.1158/1078-0432.CCR-07-2245 PG 6 WC Oncology SC Oncology GA 275LL UT WOS:000254072900002 PM 18347160 ER PT J AU Roccaro, AM Leleu, X Sacco, A Moreau, AS Hatjiharissi, E Jia, X Xu, L Ciccarelli, B Patterson, CJ Ngo, HT Russo, D Vacca, A Dammacco, F Anderson, KC Ghobrial, IM Treon, SP AF Roccaro, Aldo M. Leleu, Xavier Sacco, Antonio Moreau, Anne-Sophie Hatjiharissi, Evcloxia Jia, Xiaoying Xu, Lian Ciccarelli, Bryan Patterson, Christopher J. Ngo, Hai T. Russo, Domenico Vacca, Angelo Dammacco, Franco Anderson, Kenneth C. Ghobrial, Irene M. Treon, Steven P. TI Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenstrom's macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; CYCLE ARREST; CANCER CELLS; GROWTH-INHIBITION; SIGNALING PATHWAY; DOWN-REGULATION; COLON-CANCER; IN-VITRO; EXPRESSION AB Purpose: Resveratrol (3,4, 5-tri-hydroxy-trans-stilbene) is an antioxidant constituent of a wide variety of plant species including grapes. It has gained considerable attention because of its anticancer properties, as shown in solid and hematologic malignancies. Whether resveratrol could inhibit proliferation or induce cytotoxicity in Waldenstrom's macroglobulinemia (WM) was investigated. Experimental Design: We studied resveratrol-induced inhibition of proliferation and induction of cytotoxicity in WM cell lines,WM primary tumor cells, IgM-secreting cells, and peripheral blood mononuclear cells. The mechanisms of action and different signaling pathways involved were studied using Western blot and gene expression profile analysis. Resveratrol activity was also evaluated in the bone marrow microenvironment. We finally investigated whether or not resveratrol could have any synergistic effect if used in combination with other drugs widely used in the treatment of WM. Results: A schematic image illustrating the location and expression of the aurora kinases A, B, and C during mitosis. Resveratrol inhibited proliferation and induced cytotoxicity against WM cells, IgM-secreting cells, as well as primary WM cells, without affecting peripheral blood mononuclear cells; down-regulated Akt, extracellular signal-regulated kinase mitogen-activated protein kinases, and Wnt signaling pathways, as well as Akt activity; induced cell cycle arrest and apoptosis; and triggered c-Jun-NH2-terminal-kinase activation, followed by the activation of intrinsic and extrinsic caspase pathways. Lastly, adherence to bone marrow stromal cells did not confer protection to WM cells against resveratrol-induced cytotoxicity. Furthermore, resveratrol showed synergistic cytotoxicity when combined with dexamethasone, fludarabine, and bortezomib. Conclusion: Our data show that resveratrol has significant antitumor activity in WM, providing the framework for clinical trials in this disease. C1 [Roccaro, Aldo M.; Leleu, Xavier; Sacco, Antonio; Moreau, Anne-Sophie; Hatjiharissi, Evcloxia; Jia, Xiaoying; Xu, Lian; Ciccarelli, Bryan; Patterson, Christopher J.; Ngo, Hai T.; Anderson, Kenneth C.; Ghobrial, Irene M.; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Russo, Domenico] Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, Brescia, Italy. [Vacca, Angelo; Dammacco, Franco] Univ Bari, Sch Med, Dept Internal Med & Clin Oncol, Bari, Italy. RP Roccaro, AM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St,Mayer Bldg,M548, Boston, MA 02115 USA. EM aldo_roccaro@dfci.harvard.edu RI Russo, Domenico/C-3947-2011; Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 NR 47 TC 47 Z9 47 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 MAR 15 PY 2008 VL 14 IS 6 BP 1849 EP 1858 DI 10.1158/1078-0432.CCR-07-1750 PG 10 WC Oncology SC Oncology GA 275LL UT WOS:000254072900033 PM 18347188 ER PT J AU Zhang, YM Xu, JL Puscau, C Kim, Y Wang, X Alam, H Hu, PJ AF Zhang, Yanmei Xu, Jinling Puscau, Cristina Kim, Yongsoon Wang, Xi Alam, Hena Hu, Patrick J. TI Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity SO DEVELOPMENTAL BIOLOGY LA English DT Article DE C. elegans; dauer formation; insulin signaling; Akt; FoxO; signal transduction; steroid hormones; nuclear receptors ID AGE-1 PI3 KINASE; C-ELEGANS; LIFE-SPAN; SIGNALING PATHWAY; LARVAL DEVELOPMENT; INSULIN ACTION; FOXO PROTEINS; RECEPTOR; GENE; LONGEVITY AB Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The clatter arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals. (C) 2007 Elsevier Inc. All rights reserved. C1 [Zhang, Yanmei; Puscau, Cristina; Kim, Yongsoon; Wang, Xi; Alam, Hena; Hu, Patrick J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Xu, Jinling] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hu, Patrick J.] Univ Michigan, Sch Med, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Hu, Patrick J.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. RP Hu, PJ (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. EM pathu@umich.edu OI Hu, Patrick/0000-0002-5611-8062 FU Howard Hughes Medical Institute; NIDDK NIH HHS [K08 DK062884, K08 DK062884-01, K08 DK062884-02, K08 DK062884-03, K08 DK062884-04, K08 DK062884-05, K08-DK62884] NR 60 TC 11 Z9 31 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2008 VL 315 IS 2 BP 290 EP 302 DI 10.1016/j.ydbio.2007.12.032 PG 13 WC Developmental Biology SC Developmental Biology GA 275MJ UT WOS:000254076000003 PM 18241854 ER PT J AU Ranade, SS Yang-Zhou, D Kong, SW McDonald, EC Cook, TA Pignoni, F AF Ranade, Swati S. Yang-Zhou, Donghui Kong, Sek Won McDonald, Elizabeth C. Cook, Tiffany A. Pignoni, Francesca TI Analysis of the Otd-dependent transcriptome supports the evolutionary conservation of CRX/OTX/OTD functions in flies and vertebrates SO DEVELOPMENTAL BIOLOGY LA English DT Article DE phototransduction; photoreceptor; circadian rhythms; orthodenticle; ocelliless; Oc; visual transduction; eye evolution; photoreceptor development ID PHOTORECEPTOR-SPECIFIC EXPRESSION; BINDING PROTEIN GENE; HOMEOBOX GENE; DROSOPHILA-MELANOGASTER; ORTHODENTICLE GENE; BRAIN-DEVELOPMENT; IN-VIVO; OLIGONUCLEOTIDE ARRAYS; CELLULAR MORPHOGENESIS; CIRCADIAN ENTRAINMENT AB Homeobox transcription factors of the vertebrate CRX/OTX family play critical roles in photoreceptor neurons, the rostral brain and circadian processes. In mouse, the three related proteins, CRX, OTX1, and OTX2, fulfill these functions. In Drosophila, the single founding member of this gene family, called orthodenticle (otd), is required during embryonic brain and photoreceptor neuron development. We have used global gene expression analysis in late pupal heads to better characterize the post-embryonic functions of Otd in Drosophila. We have identified 61 genes that are differentially expressed between wild type and a viable eye-specific old mutant allete. Among them, about one-third represent potentially direct targets of Otd based on their association with evolutionarily conserved Otd-binding sequences. The spectrum of biological functions associated with these gene targets establishes Otd as a critical regulator of photoreceptor morphology and phototransduction, as well as suggests its involvement in circadian processes. Together with the well-documented role of otd in embryonic patterning, this evidence shows that vertebrate and fly genes contribute to analogous biological processes, notwithstanding the significant divergence of the underlying genetic pathways. Our findings underscore the common evolutionary history of photoperception-based functions in vertebrates and invertebrates and support the view that a complex nervous system was already present in the last common ancestor of all bilateria. (C) 2007 Elsevier Inc. All rights reserved. C1 [Ranade, Swati S.; Yang-Zhou, Donghui; Pignoni, Francesca] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02445 USA. [Ranade, Swati S.; Yang-Zhou, Donghui; Pignoni, Francesca] Massachusetts Eye & Ear Infirm, Boston, MA 02445 USA. [Kong, Sek Won] Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. [McDonald, Elizabeth C.; Cook, Tiffany A.] Univ Cincinnati, Sch Med, Div Dev Biol, Cincinnati, OH USA. [McDonald, Elizabeth C.; Cook, Tiffany A.] Harvard Univ, Sch Med, Cincinnati Childrens Hosp Med Ctr, Dept Pediat Ophthalmol, Boston, MA 02445 USA. RP Pignoni, F (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St,MEEI 507, Boston, MA 02445 USA. EM Francesca_Pignoni@meei.harvard.edu OI Cook, Tiffany/0000-0002-3100-5248 FU NEI NIH HHS [R01 EY013167-04, R01EY013167, P30EY14104, R01 EY013167-05, P30 EY014104, R01 EY013167]; NICHD NIH HHS [T32 HD046387, HD046387] NR 85 TC 25 Z9 26 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2008 VL 315 IS 2 BP 521 EP 534 DI 10.1016/j.ydbio.2007.12.017 PG 14 WC Developmental Biology SC Developmental Biology GA 275MJ UT WOS:000254076000020 PM 18241855 ER PT J AU Haiman, CA Hsu, C de Bakker, PIW Frasco, M Sheng, X Van Den Berg, D Casagrande, JT Kolonel, LN Le Marchand, L Hankinson, SE Han, J Dunning, AM Pooley, KA Freedman, ML Hunter, DJ Wu, AH Stram, DO Henderson, BE AF Haiman, Christopher A. Hsu, Chris de Bakker, Paul I. W. Frasco, Melissa Sheng, Xin Van Den Berg, David Casagrande, John T. Kolonel, Laurence N. Le Marchand, Loic Hankinson, Susan E. Han, Jiali Dunning, Alison M. Pooley, Karen A. Freedman, Matthew L. Hunter, David J. Wu, Anna H. Stram, Daniel O. Henderson, Brian E. TI Comprehensive association testing of common genetic variation in DNA repair pathway genes in relationship with breast cancer risk in multiple populations SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIETHNIC COHORT; SUSCEPTIBILITY GENE; PROTEIN FUNCTION; VARIANTS; POLYMORPHISMS; BRCA2; ALLELES; LOCI; SNPS AB Genetic association studies of multiple populations investigate a wider range of risk alleles than studies of a single ethnic group. In this study, we developed a multiethnic tagging strategy, exploiting differences in linkage disequilibrium (LD) structure between populations, to comprehensively capture common genetic variation across 60 genes spanning multiple DNA repair pathways, in five racial/ethnic populations. Over 2600 SNPs were genotyped in each population and single- and multi-marker predictors of common alleles were selected to capture the LD patterns specific to each group. Coding variants (n = 211) were genotyped to test whether combinations of putative functional variants in DNA repair pathway genes could have cumulative effects on risk. Tests of association were conducted in a multiethnic breast cancer study (2093 cases and 2303 controls), with validation of the top allelic associations (P <= 0.01) performed in additional studies of 6483 cases and 7309 controls. A variant in the FANCA gene (rs1061646, 0.15-0.68 frequency across populations) was associated with risk in the initial study (P = 0.0052), and in the replication studies (P = 0.032). In a combined analysis (8556 cases and 9605 controls), this SNP yielded an 8% increase in risk per allele. Combinations of coding variants in these genes were not associated with breast cancer and together, these data suggest that common variation in these DNA repair pathway genes are not strongly associated with breast cancer risk. The methods utilized in this study, applied to multiple populations, provide a framework for testing in association studies in diverse populations. C1 [Haiman, Christopher A.; Hsu, Chris; Frasco, Melissa; Sheng, Xin; Van Den Berg, David; Casagrande, John T.; Wu, Anna H.; Stram, Daniel O.; Henderson, Brian E.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [de Bakker, Paul I. W.; Freedman, Matthew L.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [de Bakker, Paul I. W.; Freedman, Matthew L.] MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Hankinson, Susan E.; Han, Jiali] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Hankinson, Susan E.; Han, Jiali] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Dunning, Alison M.; Pooley, Karen A.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB2 1TN, England. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. EM haiman@usc.edu RI de Bakker, Paul/B-8730-2009; OI de Bakker, Paul/0000-0001-7735-7858; Dunning, Alison Margaret/0000-0001-6651-7166 FU Cancer Research UK; NCI NIH HHS [CA049449, CA065725, CA098233, CA118447, CA17054, CA54281, CA63464]; NHGRI NIH HHS [HG002790]; NHLBI NIH HHS [HL084705] NR 41 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 15 PY 2008 VL 17 IS 6 BP 825 EP 834 DI 10.1093/hmg/ddm354 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 272BN UT WOS:000253832700006 PM 18056155 ER PT J AU Gierga, DP Riboldi, M Turcotte, JC Sharp, GC Jiang, SB Taghian, AG Chen, GTY AF Gierga, David P. Riboldi, Marco Turcotte, Julie C. Sharp, Greg C. Jiang, Steve B. Taghian, Alphonse G. Chen, George T. Y. TI Comparison of target registration errors for multiple image-guided techniques in accelerated partial breast irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol DE partial breast irradiation; target registration error; image guidance; surface imaging; X-ray localization ID LUMPECTOMY CAVITY; PATIENT SETUP; CLINICAL-EXPERIENCE; SURGICAL CLIPS; RADIOTHERAPY; SYSTEM; BRACHYTHERAPY; REPRODUCIBILITY; ACCURACY; THERAPY AB Purpose: External beam accelerated partial breast irradiation requires accurate localization of the target volume for each treatment fraction. Using the concept of target registration error (TRE), the performance of several methods of target localization was compared. Methods and Materials: Twelve patients who underwent external beam accelerated partial breast irradiation were included in this study. TRE was quantified for four methods of image guidance: standard laser-based setup, kilo-voltage imaging of the chest wall, kilo-voltage imaging of surgically implanted clips, and three-dimensional surface imaging of the breast. The use of a reference surface created from a free-breathing computed tomography scan and a reference surface directly captured with three-dimensional video imaging were compared. The effects of respiratory motion were also considered, and gating was used for 8 of 12 patients. Results: The median value of the TRE for the laser, chest wall, and clip alignment was 7.1 mm (n = 94), 5.4 mm (n = 81), and 2.4 mm (n = 93), respectively. The median TRE for gated surface imaging based on the first fraction reference surface was 3.2 mm (n = 49), and the TRE for gated surface imaging using the computed tomography-based reference surface was 4.9 mm (n = 56). The TRE for nongated surface imaging using the first fraction reference surface was 6.2 mm (n = 25). Conclusions: The TRE of surface imaging using a reference surface directly captured with three-dimensional video and the TRE for clip-based setup were within 1 mm. Gated capture is important for surface imaging to reduce the effects of respiratory motion in accelerated partial breast irradiation. (C) 2008 Elsevier Inc. C1 [Gierga, David P.; Riboldi, Marco; Turcotte, Julie C.; Sharp, Greg C.; Jiang, Steve B.; Taghian, Alphonse G.; Chen, George T. Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gierga, David P.; Riboldi, Marco; Sharp, Greg C.; Jiang, Steve B.; Taghian, Alphonse G.; Chen, George T. Y.] Harvard Univ, Sch Med, Boston, MA USA. [Riboldi, Marco] MIT, Cambridge, MA 02139 USA. [Riboldi, Marco] Politecn Milan Univ, Milan, Italy. RP Gierga, DP (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 8, Boston, MA 02114 USA. EM dgierga@partners.org RI Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 NR 28 TC 59 Z9 67 U1 0 U2 7 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 MAR 15 PY 2008 VL 70 IS 4 BP 1239 EP 1246 DI 10.1016/j.ijrobp.2007.11.020 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 273PB UT WOS:000253942900037 PM 18207662 ER PT J AU Xu, XM Capito, RM Spector, M AF Xu, Ximing Capito, Ramille M. Spector, Myron TI Plasmid size influences chitosan nanoparticle mediated gene transfer to chondrocytes SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE gene transfer; chitosan; nanoparticles; osteogenic protein-1; chondrocytes ID HUMAN ARTICULAR CHONDROCYTES; OSTEOGENIC PROTEIN-1 PROMOTES; BONE MORPHOGENETIC PROTEIN-7; GENETICALLY-MODIFIED CHONDROCYTES; DEFECTS IN-VIVO; DNA NANOPARTICLES; CARTILAGE DEFECTS; CELL-DIFFERENTIATION; MATRIX SYNTHESIS; DELIVERY-SYSTEM AB The objective of the present study was to prepare chitosan nanoparticles incorporating a relatively large plasmid encoding for osteogenic protein (OP)-1 and to determine the ability of these nanoparticles to transfect adult canine articular chondrocytes in vitro. The positive charge of chitosan acted to condense the relatively large negatively-charged OP-1 plasmid such that it could be incorporated into nanoparticles. Incorporation of the plasmid into the chitosan nanoparticles did not affect the structural integrity of the plasmid as demonstrated by gel electrophoresis. The morphology and size of the nanoparticles were found to vary with the chitosan:plasmid weight ratio. Nanoparticles formulated with a chitosan:plasmid ratio of 10:1 were of uniformly small size (less than 250 nm) and spherical shape. These nanoparticles had a positive charge of about 20 mV. FITC-labeled chitosan nanoparticles were found in virtually all of the cells after 24 h of incubation with the nanoparticles, and confocal microscopy revealed FITC-related fluorescence in the nucleus of the chondrocytes. Although transfection of the chondrocytes was demonstrated by the fluorescence of cells treated with chitosan nanoparticles containing the plasmid for the enhanced green fluorescence protein, cells transfected with nanoparticles incorporating the larger OP-1 plasmid did not show OP-1 expression measured by ELISA for up to 2 weeks in culture. These results indicate that although a large plasmid can be successfully incorporated within chitosan nanoparticles, the size of the plasmid incorporated within the nanoparticles may still significantly affect gene transfer to cells. (C) 2007 Wiley Periodicals, Inc. C1 [Xu, Ximing; Capito, Ramille M.; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Xu, Ximing] Jiangsu Univ, Sch Pharm, Dept Pharmaceut, Zhenjiang 212001, Peoples R China. [Xu, Ximing; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Capito, Ramille M.; Spector, Myron] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Shah, Ramille/E-3737-2010 NR 45 TC 18 Z9 18 U1 3 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 15 PY 2008 VL 84A IS 4 BP 1038 EP 1048 DI 10.1002/jbm.a.31479 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 264LB UT WOS:000253287700020 PM 17685397 ER PT J AU Benatuil, L Kaye, J Cretin, N Godwin, JG Cariappa, A Pillai, S Iacomini, J AF Benatuil, Lorenzo Kaye, Joel Cretin, Nathalie Godwin, Jonathan G. Cariappa, Annaiah Pillai, Shiv Iacomini, John TI Ig knock-in mice producing anti-carbohydrate antibodies: Breakthrough of B cells producing low affinity anti-self antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BOVINE CARTILAGE TRANSPLANTS; HUMAN NATURAL ANTIBODIES; GAL ANTIBODY; BONE-MARROW; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; GAL-ALPHA-1,3GAL EPITOPES; HYPERACUTE REJECTION; XENOGRAFT REJECTION; CYNOMOLGUS MONKEY; ESCAPE TOLERANCE AB Natural Abs specific for the carbohydrate Ag Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha Gal) play an important role in providing protective host immunity to various pathogens; yet little is known about how production of these or other anti-carbohydrate natural Abs is regulated. In this study, we describe the generation of Ig knock-in mice carrying functionally rearranged U chain and L chain variable region genes isolated from a B cell hybridoma producing alpha Gal-specific IgM Ab that make it possible to examine the development of B cells producing anti-carbohydrate natural Abs in the Presence or absence of alpha Gal as a self-Ag. Knock-in mice on a alpha Gal-deficient background spontaneously developed alpha Gal-specific IgM Abs of a sufficiently high titer to mediate rejection of alpha Gal expressing cardiac transplants. In the spleen of these mice, B cells expressing alpha Gal-specific IgM are located in the marginal zone. In knock-in mice that express alpha Gal, B cells expressing the knocked in BCR undergo negative selection via receptor editing. Interestingly, production of low affinity alpha Gal-specific Ab was observed in mice that express alpha Gal that carry two copies of the knocked in H chain. We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs. C1 [Iacomini, John] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Benatuil, Lorenzo; Kaye, Joel; Godwin, Jonathan G.; Iacomini, John] Childrens Hosp, Boston, MA 02115 USA. [Cretin, Nathalie] Novartis Pharma Infect Dis Transplantat & Immunol, Basel, Switzerland. [Cariappa, Annaiah; Pillai, Shiv] Massachusetts Gen Hosp East, Ctr Canc Res, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr, 221 Longwood Ave,Room LM303, Boston, MA 02115 USA. EM jiacomini@rics.bwh.harvard.edu FU NIAID NIH HHS [R01 AI050602-06, R01AI044268-09] NR 64 TC 7 Z9 7 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 MAR 15 PY 2008 VL 180 IS 6 BP 3839 EP 3848 PG 10 WC Immunology SC Immunology GA 324GS UT WOS:000257506600029 PM 18322191 ER PT J AU Hulgan, T Tebas, P Canter, JA Mulligan, K Haas, DW Dube, M Grinspoon, S Robbins, GK Motsinger, AA Kallianpur, AR AF Hulgan, Todd Tebas, Pablo Canter, Jeffrey A. Mulligan, Kathleen Haas, David W. Dube, Michael Grinspoon, Steven Robbins, Gregory K. Motsinger, Alison A. Kallianpur, Asha R. CA AIDS Clin Trials Grp 384 A5005s Study Teams TI Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID TUMOR-NECROSIS-FACTOR; SEQUENTIAL 3-DRUG REGIMENS; CELLULAR IRON HOMEOSTASIS; HEREDITARY HEMOCHROMATOSIS; FACTOR-ALPHA; HIV-1-INFECTED PATIENTS; PHENOTYPIC-EXPRESSION; ADIPOCYTE APOPTOSIS; THYMIDINE ANALOG; HIV-1 INFECTION AB Background. Antiretroviral therapy (ART)-associated lipoatrophy involves mitochondrial dysfunction. Iron metabolism impacts mitochondrial function and oxidative stress. Mitochondrial haplogroups and hemochromatosis gene (HFE) polymorphisms have been associated with ART-induced neuropathy. We assessed relationships between these variants and lipoatrophy. Methods. The AIDS Clinical Trials Group 384 study randomized ART-naive individuals to receive didanosine-stavudine or zidovudine-lamivudine, combined with efavirenz and/or nelfinavir. Substudy A5005s evaluated fat distribution by dual-energy X-ray absorptiometry (DEXA). We characterized HFE polymorphisms 845G > A and 187C > G and European mitochondrial haplogroups in A5005s participants who consented to genetic analyses. Results. Among 96 participants (58% were white, and 10% were female) with baseline and 48 or 64 week DEXA data, the median limb fat change was -8.8% (interquartile range, -28.7% to +15.6%). HFE 187C/G heterozygotes (n = 23) had less limb fat loss than 187C/C homozygotes (n = 71) (+6.1% vs. -12.5%; P = .02) and were less likely to develop lipoatrophy after adjustment for age, sex, race, and ART randomization (odds ratio, 0.31; 95% confidence interval, 0.10-0.95; P = .04). Among non-Hispanic white participants, median limb fat change was +26.1% among 5 participants with mitochondrial haplogroup J, compared with -9.7% among 49 participants with other mitochondrial haplogroups (P = .07). Conclusions. HFE 187C > G and, possibly, mitochondrial haplogroup J gave relative protection against lipoatrophy during ART in A5005s. These associations should be replicated in other studies. C1 [Hulgan, Todd; Canter, Jeffrey A.; Haas, David W.; Motsinger, Alison A.; Kallianpur, Asha R.] Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37203 USA. [Tebas, Pablo] Univ Penn, Philadelphia, PA 19104 USA. [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dube, Michael] Indiana Univ Sch Med, Indianapolis, IN USA. [Grinspoon, Steven; Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hulgan, T (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, 345 24th Ave N,Ste 105, Nashville, TN 37203 USA. EM todd.hulgan@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Hulgan, Todd/B-3947-2014; OI Hulgan, Todd/0000-0002-3339-067X; Chiesi, Antonio/0000-0002-6892-8142 FU NCCIH NIH HHS [AT002508]; NIAID NIH HHS [U01 AI068636, AI38858, AI46339, AI54999] NR 50 TC 36 Z9 38 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2008 VL 197 IS 6 BP 858 EP 866 DI 10.1086/528697 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FI UT WOS:000253773900012 PM 18419350 ER PT J AU Kuritzkes, DR Lalama, CM Ribaudo, HJ Marcial, M Meyer, WA Shikuma, C Johnson, VA Fiscus, SA D'Aquila, RT Schackman, BR Acosta, EP Gulick, RM AF Kuritzkes, Daniel R. Lalama, Christina M. Ribaudo, Heather J. Marcial, Michelle Meyer, William A., III Shikuma, Cecilia Johnson, Victoria A. Fiscus, Susan A. D'Aquila, Richard T. Schackman, Bruce R. Acosta, Edward P. Gulick, Roy M. TI Preexisting resistance to nonnucleoside reverse-transcriptase inhibitors predicts virologic failure of an efavirenz-based regimen in treatment-naive HIV-1-infected subjects SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID ANTIRETROVIRAL-DRUG-RESISTANCE; IMMUNODEFICIENCY-VIRUS TYPE-1; INITIAL TREATMENT; HIV-1 INFECTION; THERAPY; MUTATIONS; TRIAL AB A case-cohort study was used to determine the effect of baseline nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, as assessed by viral genotyping, on the response to efavirenz-containing regimens in AIDS Clinical Trials Group A5095. The sample included a random cohort of efavirenz-treated subjects plus unselected subjects who experienced virologic failure. Of 220 subjects in the random cohort, 57 (26%) had virologic failure. The prevalence of baseline NNRTI resistance was 5%. The risk of virologic failure for subjects with baseline NNRTI resistance was higher than that for subjects without such resistance (hazard ratio 2.27 [95% confidence interval], 1.15-4.49; P = .018). These results support resistance testing before starting antiretroviral therapy. C1 [Kuritzkes, Daniel R.; Marcial, Michelle] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Lalama, Christina M.; Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Meyer, William A., III] Quest Diagnost Inc, Baltimore, MD USA. [Shikuma, Cecilia] Univ Hawaii, Honolulu, HI 96822 USA. [Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama, Sch Med, Birmingham, AL USA. [Fiscus, Susan A.] Univ N Carolina, Chapel Hill, NC USA. [D'Aquila, Richard T.] Vanderbilt Univ, Nashville, TN USA. [Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Tehrapeut, 65 Landsdowne St Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org FU NCRR NIH HHS [RR024996]; NIAID NIH HHS [AI027767, AI051966, AI06836, AI068636, AI069419, AI060354, AI069452, AI069472, AI38858] NR 15 TC 101 Z9 101 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2008 VL 197 IS 6 BP 867 EP 870 DI 10.1086/528802 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FI UT WOS:000253773900013 PM 18269317 ER PT J AU Kiesewetter, DO Knudson, K Collins, M Srinivasula, S Lim, E Di Mascio, M AF Kiesewetter, Dale O. Knudson, Kathleen Collins, Matt Srinivasula, Sharat Lim, Esther Di Mascio, Michele TI Enantiomeric radiochemical synthesis of R and S (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article; Proceedings Paper CT 17th International Symposium on Radiopharmaceutical Sciences CY APR 30-MAY 04, 2007 CL Aachen, GERMANY DE fluorine-18; Tenofovir; antiretroviral drugs; HAART ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACYCLIC NUCLEOSIDE PHOSPHONATES; ANTIRETROVIRAL AGENTS; DRUG-RESISTANCE; INFECTION; DERIVATIVES; INVITRO; PHARMACOKINETICS; THERAPY; INVIVO AB Therapy for human immunodeficiency virus (HIV)-infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time-activity curves for various tissues. We have developed a fluorine-18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S-isomer exhibited significantly higher antiviral activity than the R-Isomer. In viral replication inhibition assays in human MT4 cells infected with SHIV(DJ12R), S-FPMPA had an IC(50) of 1.85 mu M (95% CI 0.8-5.53), while the R-isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine-18. The [(18)F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38 +/- 5% yield (n = 23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0 +/- 1.8 Ci/mu mol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment. C1 [Kiesewetter, Dale O.; Knudson, Kathleen] NIBIB, NIH, PRG, Positron Emiss Tomog Radiochem Grp, Bethesda, MD 20892 USA. [Collins, Matt] Bioqual, Rockville, MD USA. [Srinivasula, Sharat] NCI Frederick, SAIC Frederick, Biostat Res Branch, Ft Detrick, MD 21702 USA. [Lim, Esther] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Di Mascio, Michele] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIBIB, NIH, PRG, Positron Emiss Tomog Radiochem Grp, 10 Ctr Dr MSC 1180,10-1C401, Bethesda, MD 20892 USA. EM dk7k@nih.gov FU Intramural NIH HHS [Z01 EB000001-03]; NCI NIH HHS [N01CO12400] NR 32 TC 3 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAR 15 PY 2008 VL 51 IS 3-4 BP 187 EP 194 DI 10.1002/jlcr.1505 PG 8 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 299BI UT WOS:000255730400011 PM 19724660 ER PT J AU Koch, M Nielsen, GP Yoon, SS AF Koch, Moritz Nielsen, G. Petur Yoon, Sam S. TI Malignant tumors of blood vessels: Angiosarcomas, hemangioendotheliomas, and hemangioperictyomas SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE angiosarcoma; hemangioendothelioma; hemangiopericytoma ID SOFT-TISSUE SARCOMAS; HEPATIC EPITHELIOID HEMANGIOENDOTHELIOMA; SOLITARY FIBROUS TUMOR; OF-THE-LITERATURE; VASCULAR TUMORS; CUTANEOUS ANGIOSARCOMA; LIVER-TRANSPLANTATION; LIPOSOMAL DOXORUBICIN; SURGICAL THERAPY; BONE AB Sarcomas that arise from or resemble the components of blood vessels are uncommon and include angiosarcomas, hemangioendotheliomas, and hemangiopericytomas. This article reviews the management of these three types of sarcomas. Diagnosis can sometimes be difficult, with the diagnosis of hemangiopericytoma versus solitary fibrous tumor currently in debate. Each of these sarcomas subtypes has certain unique clinical traits. The mainstay of treatment is surgical resection, sometimes combined with radiation therapy. Adjuvant chemotherapy is unproven but can be considered. For patients with advanced disease, various chemotherapeutic regimens may result in meaningful responses in a minority of patients. C1 [Yoon, Sam S.] Harvard Univ, Sch Med, Div Surg Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koch, Moritz] Univ Heidelberg, Dept Surg, Heidelberg, Germany. [Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yoon, SS (reprint author), Harvard Univ, Sch Med, Div Surg Oncol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org NR 89 TC 45 Z9 56 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAR 15 PY 2008 VL 97 IS 4 BP 321 EP 329 DI 10.1002/jso.20973 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 273WI UT WOS:000253962400004 PM 18286475 ER PT J AU Nascimento, AF Raut, CP AF Nascimento, Alessandra F. Raut, Chandrajit P. TI Diagnosis and management of pleomorphic sarcomas (so-called "MFH") in adults SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE malignant fibrous histiocytoma; myxofibrosarcoma; pleomorphic sarcoma; giant cell; liposarcoma; leiomyosarcoma; rhabdomyosarcoma ID MALIGNANT FIBROUS HISTIOCYTOMA; SOFT-TISSUE SARCOMAS; COMPARATIVE GENOMIC HYBRIDIZATION; GIANT-CELL TUMOR; ADJUVANT RADIATION-THERAPY; LIMB-SPARING SURGERY; HIGH-DOSE IFOSFAMIDE; PROGNOSTIC FACTORS; CLINICOPATHOLOGICAL ANALYSIS; POSTOPERATIVE RADIOTHERAPY AB The existence of "malignant fibrous histiocytoma" ("MFH") as a distinct entity is controversial. Previously accepted as the most common sarcoma affecting adults, it is now known to comprise a heterogeneous group of tumors without a specific known line of differentiation. Reclassification of many tumors in this group afforded better prognostication, but traditional treatments still apply. Pleomorphic soft tissue tumors for which a line of differentiation is debatable are presently categorized as undifferentiated pleomorphic sarcoma. C1 [Nascimento, Alessandra F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nascimento, Alessandra F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Dept Surg, Brigham & Womens Hosp, Ctr Sarcoma & Bone Oncol, Boston, MA USA. RP Nascimento, AF (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM anascimento@partners.org NR 96 TC 38 Z9 44 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAR 15 PY 2008 VL 97 IS 4 BP 330 EP 339 DI 10.1002/jso.20972 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 273WI UT WOS:000253962400005 PM 18286476 ER PT J AU Gaziano, TA Young, CR Fitzmaurice, G Atwood, S Gaziano, JM AF Gaziano, Thomas A. Young, Cynthia R. Fitzmaurice, Garrett Atwood, Sidney Gaziano, J. Michael TI Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort SO LANCET LA English DT Article ID CORONARY-HEART-DISEASE; SERUM-CHOLESTEROL CONCENTRATION; MIDDLE-INCOME COUNTRIES; C-REACTIVE PROTEIN; GLOBAL BURDEN; PREDICTION; POPULATION; HYPERTENSION; PREVENTION; EVENTS AB Background Around 80% of all cardiovascular deaths occur in developing countries. Assessment of those patients at high risk is an important strategy for prevention. Since developing countries have limited resources for prevention strategies that require laboratory testing, we assessed if a risk prediction method that did not require any laboratory tests could be as accurate as one requiring laboratory information. Methods The National Health and Nutrition Examination Survey (NHANES) was a prospective cohort study of 14407 US participants aged between 25-74 years at the time they were first examined (between 1971 and 1975). Our follow-up study population included participants with complete information on these surveys who did not report a history of cardiovascular disease (myocardial infarction, heart failure, stroke, angina) or cancer, yielding an analysis dataset N=6186. We compared how well either method could predict first-time fatal and non-fatal cardiovascular disease events in this cohort. For the laboratory-based model, which required blood testing, we used standard risk factors to assess risk of cardiovascular disease: age, systolic blood pressure, smoking status, total cholesterol, reported diabetes status, and current treatment for hypertension. For the non-laboratory-based model, we substituted body-mass index for cholesterol. Findings in the cohort of 6186, there were 1529 first-time cardiovascular events and 578 (38%) deaths due to cardiovascular disease over 21 years. In women, the laboratory-based model was 0.831. In men, the results were similar (0.784 for the laboratory-based model and 0.783 for the non-laboratory-based model). Results were similar between the laboratory-based and non-laboratory-based models in both men and women when restricted to fatal events only. Interpretation A method that uses non-laboratory-based risk factors predicted cardiovascular events as accurately as one that relied on laboratory-based values. This approach could simplify risk assessment in situations where laboratory testing is inconvenient or unavailable. C1 [Gaziano, Thomas A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Atwood, Sidney] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Young, Cynthia R.] Harvard Univ, Sch Med, Boston, MA USA. [Fitzmaurice, Garrett] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02178 USA. [Gaziano, Thomas A.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Gaziano, TA (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM tgaziano@partners.org FU FIC NIH HHS [K01 TW007141-01, 1K01TW007141-01, K01 TW007141, K01 TW007141-02, K01 TW007141-03, K01 TW007141-04] NR 39 TC 147 Z9 153 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 15 PY 2008 VL 371 IS 9616 BP 923 EP 931 DI 10.1016/S0140-6736(08)60418-3 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 275FH UT WOS:000254056800029 PM 18342687 ER PT J AU Raymond, D Saunders-Pullman, R Aguiar, PD Schule, B Kock, N Friedman, J Harris, J Ford, B Frucht, S Heiman, GA Jennings, D Doherty, D Brin, MF Brin, DD Multhaupt-Buell, T Lang, AE Kurlan, R Klein, C Ozelius, L Bressman, S AF Raymond, Deborah Saunders-Pullman, Rachel Aguiar, Patricia de Carvalho Schule, Birgitt Kock, Norman Friedman, Jennifer Harris, Juliette Ford, Blair Frucht, Steven Heiman, Gary A. Jennings, Danna Doherty, Dana Brin, Mitchell F. Brin, Deborah de Leon Multhaupt-Buell, Trisha Lang, Anthony E. Kurlan, Roger Klein, Christine Ozelius, Laurie Bressman, Susan TI Phenotypic spectrum and sex effects in eleven myoclonus-dystonia families with epsilon-sarcoglycan mutations SO MOVEMENT DISORDERS LA English DT Article DE myoclonus dystonia; epsilon-sarcoglycan; SGCE; phenotype ID OBSESSIVE-COMPULSIVE DISORDER; ALCOHOL DEPENDENCE; GENE-MUTATIONS AB Myoclonus-dystonia (M-D) due to SGCE mutations is characterized by early onset myoclonic jerks, often associated with dystonia. Penetrance is influenced by parental sex, but other sex effects have not been established. In 42 affected individuals from 11 families with identified mutations, we found that sex was highly associated with age at onset regardless of mutation type; the median age onset for girls was 5 years versus 8 years for boys (P < 0.0097). We found no association between mutation type and phenotype. (C) 2008 Movement Disorder Society. C1 [Raymond, Deborah; Saunders-Pullman, Rachel; Brin, Deborah de Leon; Bressman, Susan] Beth Israel Deaconess Med Ctr, Alan & Barbara Mirken Dept Neurol, New York, NY 10003 USA. [Saunders-Pullman, Rachel; Bressman, Susan] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Aguiar, Patricia de Carvalho] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. [Aguiar, Patricia de Carvalho] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, Brazil. [Schule, Birgitt] Parkinsons Inst, Dept Clin Res, Sunnyvale, CA USA. [Kock, Norman; Klein, Christine] Univ Lubeck, Dept Neurol, Lubeck, Germany. [Kock, Norman; Klein, Christine] Univ Lubeck, Dept Human Genet, Lubeck, Germany. [Friedman, Jennifer] Rady Childrens Hosp, Dept Neurol, San Diego, CA USA. [Friedman, Jennifer; Multhaupt-Buell, Trisha] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Harris, Juliette; Ford, Blair; Frucht, Steven] Columbia Univ, Dept Neurol, New York, NY USA. [Heiman, Gary A.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Jennings, Danna] Inst Neurodegenerat Disorders, New Haven, CT USA. [Doherty, Dana] Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. [Brin, Mitchell F.] Univ Calif Irvine & Allergan, LLC, Irvine, CA USA. [Lang, Anthony E.] Univ Toronto, Toronto Western Hosp, Dept Med Neurol, Toronto, ON, Canada. [Kurlan, Roger] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Ozelius, Laurie] Mt Sinai Sch Med, Dept Genet & Genome Sci, New York, NY USA. RP Raymond, D (reprint author), Beth Israel Deaconess Med Ctr, Alan & Barbara Mirken Dept Neurol, 10 Union Sq E,Suite 5J, New York, NY 10003 USA. EM draymond@chpnet.org RI de Carvalho Aguiar, Patricia/E-8520-2010 OI de Carvalho Aguiar, Patricia/0000-0003-2957-9573 FU NINDS NIH HHS [NS37409, NS26656] NR 21 TC 22 Z9 23 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR 15 PY 2008 VL 23 IS 4 BP 588 EP 592 DI 10.1002/mds.21785 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 285WX UT WOS:000254808000017 PM 18175340 ER PT J AU Gao, X Chen, H Schwarzschild, MA Logroscino, G Ascherio, A AF Gao, Xiang Chen, Honglei Schwarzschild, Michael A. Logroscino, Giancarlo Ascherio, Alberto TI Perceived imbalance and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE perceived imbalance; Parkinson's disease; prospective study ID PHYSICAL-ACTIVITY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; REPRODUCIBILITY; VALIDITY; FREQUENCY AB We prospectively examined associations between perceived imbalance and Parkinson's disease (PD) risk in the Health Professional Follow-up Study (HPFS), and Nurses' Health Study (NHS). We included 39,087 men and 82,299 women free of PD at baseline (1990) in the current analyses. We documented 449 incident PD cases during 12 years followup. Subjects who reported difficulty with balance before 1990 (baseline) were 1.8 more times likely to develop PD, relative to those who reported no balance difficulty (pooled multivariate RR = 1.8; 95% CI: 1.3, 2.5; P < 0.0001). When we further examined associations between perceived imbalance at baseline and PD onset during different time periods, we found a significant elevation of PD risk only during the first 4 years of follow-up. This result suggests that the imbalance may in some cases be an early sign of PD, and may represent the onset of motor symptoms although they have not been clinically recognized. (C) 2008 Movement Disorder Society. C1 [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Logroscino, Giancarlo; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Gao, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM xgao@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517-01A2, R01 NS048517] NR 14 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR 15 PY 2008 VL 23 IS 4 BP 613 EP 616 DI 10.1002/mds.21919 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 285WX UT WOS:000254808000024 PM 18181208 ER PT J AU Kremen, WS Seidman, LJ Faraone, SV Tsuang, MT AF Kremen, William S. Seidman, Larry J. Faraone, Stephen V. Tsuang, Ming T. TI IQ decline in cross-sectional studies of schizophrenia: Methodology and interpretation SO PSYCHIATRY RESEARCH LA English DT Article DE IQ decline; preserved IQ; executive dysfunction ID MONOZYGOTIC TWINS DISCORDANT; NEUROPSYCHOLOGICAL FUNCTION; BIRTH COHORT; COMPROMISED INTELLECT; MATCHING FALLACY; 3 RS; RISK; CHILDHOOD; PSYCHOSES; IMPAIRMENT AB Some researchers have compared neuropsychological performance ill schizophrenia groups with and without presumed IQ decline. Inherent in this approach is an assumption that group differences are due to different IQ trajectories (stable vs. declining), bill: neuropsychological differences could be a function of current IQ regardless of the presence or absence of previous IQ decline. We examined this issue in 93 normal controls and in 80 patients classified as having preserved (27.5%), deteriorated (50%), or compromised (22.5%) intellect based on IQ and reading recognition-IQ difference scores. We also examined group differences in verbal and performance IQ. Deteriorated patients had the largest verbal performance-IQ differences. They were more neuropsychologically impaired than the preserved group (average effect size=0.43), but deteriorated patients also had significantly lower Current IQs. When Subgroups Of preserved and deteriorated patients with equivalent current IQs were compared, neuropsychological differences were essentially eliminated (average effect size=0.10)-, however, both groups were significantly more impaired than controls with similar IQs. Neuropsychological impairment, even in patients with apparently preserved IQ, is consistent with a prefrontal-dysexecutive syndrome. Overall, these results strongly suggest that differences in current neuropsychological function in schizophrenia are attributable primarily to Current IQ instead of to IQ trajectory over time. (C) 2008 Published by Elsevier Ireland Ltd. C1 [Kremen, William S.; Tsuang, Ming T.] Univ Calif San Diego, Sch Med, Ctr Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02214 USA. [Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Seidman, Larry J.; Tsuang, Ming T.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. [Faraone, Stephen V.; Tsuang, Ming T.] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. [Faraone, Stephen V.; Tsuang, Ming T.] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.; Tsuang, Ming T.] Vet Affairs San Diego Healthcare Syst, La Jolla, CA 92161 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Sch Med, Ctr Behav Genom, Dept Psychiat, 9500 Gilman Dr MC 0738, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIA NIH HHS [R01 AG018386]; NIMH NIH HHS [MH43518-01, MH46318] NR 66 TC 24 Z9 24 U1 1 U2 2 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 MAR 15 PY 2008 VL 158 IS 2 BP 181 EP 194 DI 10.1016/j.psychres.2006.01.022 PG 14 WC Psychiatry SC Psychiatry GA 287JO UT WOS:000254913600009 PM 18237787 ER PT J AU Huang, XL Moore, DJ Mohiuddin, M Lian, MM Kim, JI Sonawane, S Wang, J Gu, Y Yeh, HD Markmann, JF Deng, SP AF Huang, Xiaolun Moore, Danie J. Mohiuddin, Mohammad Lian, Moh-Moh Kim, James I. Sonawane, Samsher Wang, Jing Gu, Yi Yeh, Heidi Markmann, James F. Deng, Shaoping TI Inhibition of ICAM-1/LFA-1 interactions prevents B-cell-dependent anti-CD45RB-induced transplantation tolerance SO TRANSPLANTATION LA English DT Article DE tolerance; transplantation; ICAM; LFA-1; anti-CD45RB ID ISLET ALLOGRAFT SURVIVAL; NONOBESE DIABETIC MICE; CD45RB MONOCLONAL-ANTIBODY; CD8(+) T-CELLS; CUTTING EDGE; CARDIAC ALLOGRAFT; LYMPHOCYTES; AUTOIMMUNITY; ROLES; MECHANISMS AB Background. Allogeneic tolerance can be reliably obtained with monoclonal antibody therapy targeting CD45RB. Although regulatory T cells play an important role in the mechanism, we have recently demonstrated the active participation of host B lymphocytes. After anti-CD45RB therapy, B lymphocytes demonstrate phenotypic alterations that include up-regulation of CD54 (intercellular adhesion molecule [ICAM]-1). We have investigated the hypothesis that alteration in ICAM-1expression is required for tolerance induction. Materials and Methods. Recipients of heterotopic allogeneic cardiac grafts (C3H donors into 136 recipients) were treated with anti-CD45RB, anti-ICAM, anti-lymphocyte function-associated antigen-1 (LFA), or the combination of these agents. These data were extended by performing allogeneic cardiac transplants into ICAM(-/-) or LFA(-/-) recipients treated with a 5-day course of anti-CD45RB. Finally, B-cell-deficient animals were reconstituted with ICAM(-/-) splenocytes to create a recipient with a selective deficiency of ICAM-1restricted to the B-cell compartment. Results. Anti-CD45RB alone or the combination of anti -LFA/anti-ICAM reliably induced transplantation tolerance. However, the triple combination was routinely unsuccessful and induced long-term graft survival in no recipients. ICAM-deficient or LFA-deficient recipients were also resistant to tolerance induced by anti-CD45RB. Finally, transfer of control splenocytes to B-cell-deficient recipients permitted anti-CD45RB-induced tolerance, whereas transfer of ICAM(-/-) cells was unable to support tolerance induction. Conclusions. Expression of ICAM-1 by B lymphocytes and interaction with LFA-1 form a central aspect of transplantation tolerance induced by anti-CD45RB therapy. These data further elucidate the cellular mechanisms used by B lymphocytes in the induction of transplantation tolerance. C1 [Kim, James I.; Gu, Yi; Yeh, Heidi; Markmann, James F.; Deng, Shaoping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Huang, Xiaolun; Moore, Danie J.; Mohiuddin, Mohammad; Lian, Moh-Moh; Sonawane, Samsher; Wang, Jing] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Gu, Yi; Deng, Shaoping] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Peoples R China. RP Deng, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM sdeng1@partners.org RI Moore, Daniel/A-4924-2008; Mohiuddin, Muhammad/M-4642-2013 OI Moore, Daniel/0000-0002-6889-9345; Mohiuddin, Muhammad/0000-0003-4654-783X FU NIAID NIH HHS [AI-057851, R01 AI057851, R56 AI057851]; NIDDK NIH HHS [P01 DK049814, P01-DK-49814, F32 DK083161, DK54215, F32 DK083161-01, K01 DK079207-01, K01 DK079207] NR 37 TC 16 Z9 22 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2008 VL 85 IS 5 BP 675 EP 680 DI 10.1097/TP.0b0136181663422 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 274YA UT WOS:000254037500005 PM 18337659 ER PT J AU Chan, JY Takeda, M Briggs, LE Graham, ML Lu, JT Horikoshi, N Weinberg, EO Aoki, H Sato, N Chien, KR Kasahara, H AF Chan, Jason Y. Takeda, Morihiko Briggs, Laura E. Graham, Megan L. Lu, Jonathan T. Horikoshi, Nobuo Weinberg, Ellen O. Aoki, Hiroki Sato, Naruki Chien, Kenneth R. Kasahara, Hideko TI Identification of cardiac-specific myosin light chain kinase SO CIRCULATION RESEARCH LA English DT Article DE kinase; transcription; contraction ID SMOOTH-MUSCLE MYOSIN; PERFUSED RAT-HEART; SKELETAL-MUSCLE; PHOSPHORYLATION; AUTOPHOSPHORYLATION; CONTRACTION; ACTIVATION; PROTEIN; LOCALIZATION; POTENTIATION AB Two myosin light chain (MLC) kinase (MLCK) proteins, smooth muscle (encoded by mylk1 gene) and skeletal (encoded by mylk2 gene) MLCK, have been shown to be expressed in mammals. Even though phosphorylation of its putative substrate, MLC2, is recognized as a key regulator of cardiac contraction, a MLCK that is preferentially expressed in cardiac muscle has not yet been identified. In this study, we characterized a new kinase encoded by a gene homologous to mylk1 and -2, named cardiac MLCK, which is specifically expressed in the heart in both atrium and ventricle. In fact, expression of cardiac MLCK is highly regulated by the cardiac homeobox protein Nkx2-5 in neonatal cardiomyocytes. The overall structure of cardiac MLCK protein is conserved with skeletal and smooth muscle MLCK; however, the amino terminus is quite unique, without significant homology to other known proteins, and its catalytic activity does not appear to be regulated by Ca2+/calmodulin in vitro. Cardiac MLCK is phosphorylated and the level of phosphorylation is increased by phenylephrine stimulation accompanied by increased level of MLC2v phosphorylation. Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction. C1 [Chan, Jason Y.; Takeda, Morihiko; Briggs, Laura E.; Graham, Megan L.; Kasahara, Hideko] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. [Lu, Jonathan T.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Horikoshi, Nobuo] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Weinberg, Ellen O.] Boston Univ, Med Ctr, Boston, MA USA. [Aoki, Hiroki] Yamaguchi Univ, Sch Med, Dept Mol Cardiovasc Biol, Ube, Yamaguchi 755, Japan. [Sato, Naruki] Chiba Univ, Fac Sci, Dept Biol, Chiba 260, Japan. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Kasahara, H (reprint author), Univ Florida, Coll Med, Dept Physiol & Funct Genom, 1600 SW,Archer Rd, Gainesville, FL 32610 USA. EM hkasahar@phys.med.ufl.edu FU NHLBI NIH HHS [R01 HL081577-03, R01 HL081577-04, R01 HL081577-02, HL081577, R01 HL081577, R01 HL081577-01] NR 35 TC 78 Z9 81 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 14 PY 2008 VL 102 IS 5 BP 571 EP 580 DI 10.1161/CIRCRESAHA.107.161687 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 274GJ UT WOS:000253989500011 PM 18202317 ER PT J AU Christofk, HR Vander Heiden, MG Wu, N Asara, JM Cantley, LC AF Christofk, Heather R. Vander Heiden, Matthew G. Wu, Ning Asara, John M. Cantley, Lewis C. TI Pyruvate kinase M2 is a phosphotyrosine-binding protein SO NATURE LA English DT Article ID ALLOSTERIC REGULATION; RECEPTOR KINASE; CELL-GROWTH; PHOSPHORYLATION; INHIBITION; ENZYMES AB Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine- binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 ( fetal) isoform of pyruvate kinase ( PKM2), binds directly and selectively to tyrosine- phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose- 1,6- bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine- binding form of pyruvate kinase is critical for rapid growth in cancer cells. C1 [Christofk, Heather R.; Vander Heiden, Matthew G.; Wu, Ning; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lcantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [T32 CA009172]; NIGMS NIH HHS [R01 GM056203] NR 17 TC 455 Z9 480 U1 14 U2 81 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 13 PY 2008 VL 452 IS 7184 BP 181 EP U27 DI 10.1038/nature06667 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273JG UT WOS:000253925600033 PM 18337815 ER PT J AU Christofk, HR Vander Heiden, MG Harris, MH Ramanathan, A Gerszten, RE Wei, R Fleming, MD Schreiber, SL Cantley, LC AF Christofk, Heather R. Vander Heiden, Matthew G. Harris, Marian H. Ramanathan, Arvind Gerszten, Robert E. Wei, Ru Fleming, Mark D. Schreiber, Stuart L. Cantley, Lewis C. TI The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth SO NATURE LA English DT Article ID ALLOSTERIC REGULATION; AEROBIC GLYCOLYSIS; INHIBITION; CELLS AB Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago(1). How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase(2). Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 ( adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo. C1 [Christofk, Heather R.; Vander Heiden, Matthew G.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, Marian H.; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramanathan, Arvind; Gerszten, Robert E.; Wei, Ru; Schreiber, Stuart L.] Harvard Univ, Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA. [Ramanathan, Arvind; Gerszten, Robert E.; Wei, Ru; Schreiber, Stuart L.] MIT, Cambridge, MA 02142 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. [Gerszten, Robert E.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lcantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU Howard Hughes Medical Institute; NCI NIH HHS [T32 CA009172]; NIGMS NIH HHS [R01 GM056203] NR 19 TC 1138 Z9 1186 U1 35 U2 193 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 13 PY 2008 VL 452 IS 7184 BP 230 EP U74 DI 10.1038/nature06734 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273JG UT WOS:000253925600043 PM 18337823 ER PT J AU Abramson, JS Kotton, CN Elias, N Sahani, DV Hasserjian, RP Den, RB Elias, N Rosenberg, ES Attar, E AF Abramson, Jeremy S. Kotton, Camille N. Elias, Nahel Sahani, Dushyant V. Hasserjian, Robert P. Den, Robert B. Elias, Nahel Rosenberg, Eric S. Attar, Eyal TI A man with fever, abdominal pain, and pancytopenia after renal transplantation - Post-transplant lymphoproliferative disorder: Hepatosplenic T-cell lymphoma, gamma/delta type SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SOLID-ORGAN TRANSPLANTATION; OF-THE-LITERATURE; GAMMA-DELTA; THROMBOTIC MICROANGIOPATHY; CLINICOPATHOLOGICAL ENTITY; IMMUNOCOMPROMISED PATIENTS; ISOCHROMOSOME 7Q; UNITED-STATES; RECIPIENTS; DISEASE C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kotton, Camille N.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Abramson, Jeremy S.; Kotton, Camille N.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Elias, Nahel] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Sahani, Dushyant V.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 43 TC 4 Z9 5 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 MAR 13 PY 2008 VL 358 IS 11 BP 1176 EP 1187 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 272RK UT WOS:000253877200012 PM 18337607 ER PT J AU Meier, A Bagchi, A Sidhu, HK Alter, G Suscovich, TJ Kavanagh, DG Streeck, H Brockman, MA LeGall, S Heilman, J Altfeld, M AF Meier, Angela Bagchi, Aranya Sidhu, Harlyn K. Alter, Galit Suscovich, Todd J. Kavanagh, Daniel G. Streeck, Hendrik Brockman, Mark A. LeGall, Sylvie Heilman, Judith Altfeld, Marcus TI Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR ligands SO AIDS LA English DT Article ID DISEASE PROGRESSION; T-CELLS; INFECTION AB Increased PD-L1 expression has been reported in HIV-1-infected individuals, but the mechanisms leading to PD-L1 upregulation remain to be elucidated. Here we demonstrate that HIV-1-derived Toll-like receptor (TLR)7/8 ligands can induce MyD88-dependent upregulation of PD-L1 on plasmacytoid dendritic cells, myeloidic dendritic cells and monocytes. These data suggest a mechanism through which HIV-1-derived TLR ligands might contribute to the functional impairment of virus-specific PD-1-positive T cells by inducing the upregulation of PD-L1 on antigen-presenting cells. C1 [Meier, Angela; Sidhu, Harlyn K.; Alter, Galit; Suscovich, Todd J.; Kavanagh, Daniel G.; Streeck, Hendrik; Brockman, Mark A.; LeGall, Sylvie; Altfeld, Marcus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. [Bagchi, Aranya; Heilman, Judith] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Meier, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. OI Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [R21 AI071806, 1R21AI071806-01A2, F32 AI058457, R21 AI071806-01A2] NR 11 TC 49 Z9 55 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 12 PY 2008 VL 22 IS 5 BP 655 EP 658 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 284AE UT WOS:000254676800015 PM 18317010 ER PT J AU Putnam, MC Wig, GS Grafton, ST Kelley, WM Gazzaniga, MS AF Putnam, Mary Colvin Wig, Gagan S. Grafton, Scott T. Kelley, William M. Gazzaniga, Michael S. TI Structural organization of the corpus callosum predicts the extent and impact of cortical activity in the nondominant hemisphere SO JOURNAL OF NEUROSCIENCE LA English DT Article DE corpus callosum; laterality; hemispheric asymmetry; memory; individual differences; neuroimaging ID DIFFUSION-TENSOR MRI; WHITE-MATTER DAMAGE; SEX-DIFFERENCES; DIFFERENTIAL VULNERABILITY; CEREBRAL HEMISPHERES; OLDER-ADULTS; LEFT-HANDERS; IN-VIVO; BRAIN; ASYMMETRY AB Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) were combined to examine the relationship between callosal organization and cortical activity across hemispheres. Healthy young adults performed an incidental verbal encoding task (semantic judgments on words) while undergoing fMRI. Consistent with previous studies, the verbal encoding task was associated with left-lateralized activity in the inferior prefrontal cortex (LIPFC). When subjects were divided into two groups based on fractional anisotropy (FA) values in the anterior corpus callosum (DTI), individuals with low anterior callosal FA were found to exhibit greater activity in a homologous region within the right inferior prefrontal cortex (RIPFC) relative to those with high anterior callosal FA. Interestingly, whereas the magnitude of RIPFC activity did not negatively impact subsequent verbal memory performance for individuals with low anterior callosal FA, greater RIPFC activity during verbal encoding was associated with poorer subsequent memory performance for individuals with high anterior callosal FA. Together, these findings provide novel evidence that individual differences in callosal organization are related to the extent of nondominant cortical activity during performance during a lateralized task, and further, that this relationship has consequences on behavior. C1 [Putnam, Mary Colvin; Wig, Gagan S.; Grafton, Scott T.; Kelley, William M.; Gazzaniga, Michael S.] Dartmouth Coll, Ctr Cognit Neurosci, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. RP Putnam, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mputnam1@partners.org FU NINDS NIH HHS [P50 NS17778, R01NS031443-10A2] NR 48 TC 48 Z9 52 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 12 PY 2008 VL 28 IS 11 BP 2912 EP 2918 DI 10.1523/JNEUROSCI.2295-07.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 274AK UT WOS:000253973600028 PM 18337422 ER PT J AU Shaw, LJ Berman, DS Maron, DJ Mancini, J Hayes, SW Hartigan, PM Weintraub, WS O'Rourke, RA Dada, M Spertus, JA Chaitman, BR Friedman, J Slomka, P Heller, GV Germano, G Gosselin, G Berger, P Kostuk, WJ Schwartz, RG Knudtson, M Veledar, E Bates, ER McCallister, B Teo, KK Boden, WE AF Shaw, Leslee J. Berman, Daniel S. Maron, David J. Mancini, John Hayes, Sean W. Hartigan, Pamela M. Weintraub, William S. O'Rourke, Robert A. Dada, Marcin Spertus, John A. Chaitman, Bernard R. Friedman, John Slomka, Piotr Heller, Gary V. Germano, Guido Gosselin, Gilbert Berger, Peter Kostuk, William J. Schwartz, Ronald G. Knudtson, Merill Veledar, Emir Bates, Eric R. McCallister, Benjamin Teo, Koon K. Boden, William E. CA COURAGE Invest TI Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden - Results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy SO CIRCULATION LA English DT Article DE ischemia; perfusion; prevention; prognosis ID EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-PERFUSION SPECT; INCREMENTAL PROGNOSTIC VALUE; ARTERY-DISEASE; EJECTION FRACTION; RISK; STRATIFICATION; QUANTIFICATION; INFARCTION; SEVERITY AB Background-Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS). Methods and Results-Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean = 374 +/- 50 days) after randomization using paired exercise (n = 84) or vasodilator stress (n = 230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered >= 10% myocardium. The primary end point was >= 5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (-2.7%; 95% confidence interval, -1.7%, -3.8%) than with OMT (-0.5%; 95% confidence interval, -1.6%, 0.6%; P < 0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%; P=0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P = 0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction (P = 0.037 [risk-adjusted P = 0.26]), particularly if baseline ischemia was moderate to severe (P = 0.001 [risk-adjusted P=0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to >= 10% residual ischemia on follow- up MPS (P=0.002 [risk-adjusted P=0.09]). Conclusions-In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of >= 5% ischemia reduction with OMT with or without coronary revascularization. C1 [Shaw, Leslee J.; Veledar, Emir] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Berman, Daniel S.; Hayes, Sean W.; Friedman, John; Slomka, Piotr; Germano, Guido] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. [Hartigan, Pamela M.] Vet Affairs Connecticut Healthcare Syst, Vet Affairs Cooperat Studies Program Coordinating, West Haven, CT USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [O'Rourke, Robert A.; Heller, Gary V.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Spertus, John A.; McCallister, Benjamin] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Chaitman, Bernard R.] St Louis Univ, St Louis, MO 63103 USA. [Gosselin, Gilbert] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Berger, Peter] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. [Kostuk, William J.] London Hlth Sci Ctr, London, ON, Canada. [Schwartz, Ronald G.] Univ Rochester, Rochester, NY USA. [Knudtson, Merill] Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. [Bates, Eric R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Teo, Koon K.] McMaster Univ, Hamilton, ON, Canada. [Boden, William E.] SUNY Buffalo, Western New York Vet Affairs Healthcare Network, Buffalo Gen Hosp, Buffalo, NY 14260 USA. RP Shaw, LJ (reprint author), Emory Univ, EPICORE, Suite 1-N,1256 Briarchiff Rd NE, Atlanta, GA 30306 USA. EM leslee.shaw@emory.edu RI Veledar, Emir/K-2808-2012 OI Veledar, Emir/0000-0002-3831-5433 NR 21 TC 683 Z9 716 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 11 PY 2008 VL 117 IS 10 BP 1283 EP 1291 DI 10.1161/CIRCULATIONAHA.107.743963 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 272KU UT WOS:000253859100007 PM 18268144 ER PT J AU Praskova, M Xia, F Avruch, J AF Praskova, Maria Xia, Fan Avruch, Joseph TI MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE; TUMOR-SUPPRESSOR; PROMOTES APOPTOSIS; HIPPO; PATHWAY; LATS1; CYTOKINESIS; ACTIVATION; DROSOPHILA; CASPASE AB Background: MST1 and MST2 are the mammalian Ste20-related protein kinases most closely related to Drosophila Hippo, a major regulator of cell proliferation and survival during development. Overexpression of MST1 or MST2 in mammalian cells is proapototic; however, little is known concerning the physiologic regulation of the endogenous MST1/MST2 kinases, their role in mammalian cell proliferation, or the identity of the MST1/MST2 substrates critical to proliferative regulation. Results: We show that MST1 and MST2 activity increases during mitosis, especially in nocodazole-arrested mitotic cells, where these kinases exhibit both an increase in both abundance and activation. MST1 and MST2 also can be activated nonphysiologically by okadaic acid or H2O2. The MOBKL1A and MOBKL1B polypeptides, homologs of the Drosophila MATS polypeptide, are identified as preferred MST1/MST2 substrates in vitro and are phosphorylated in cells in an MST1/MST2-dependent manner in mitosis and in response to okadaic acid or H2O2. MST1/MST2-catalyzed MOBKL1A/MOBKL1B phosphorylation alters the ability of MOBKL1A/MOBKL1 B to bind and regulate downstream targets such as the NDR-family protein kinases. Thus, MOBKL1A/MOBKL1 B phosphorylation in cells promotes MOBKL1A/MOBKL1B binding to the LATS1 kinase and enables H2O2-Stimulated LATS1 activation loop phosphorylation. Most importantly, replacement of endogenous MOBKL1A/MOBKL1B by a nonphosphorylatable mutant is sufficient to accelerate cell proliferation substantially by speeding progression through G1/S as well as mitotic exit. Conclusions: These results establish that MST1 and MST2 are activated in mitosis and catalyze the mitotic phosphorylation of MOBKL1A/MOBKL1B. MOBKL1A/MOBKL1B phosphorylation, in turn, is sufficient to inhibit proliferation through actions at several points in the cell cycle. C1 [Praskova, Maria; Xia, Fan; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Praskova, Maria; Xia, Fan; Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. [Praskova, Maria; Xia, Fan; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Praskova, Maria; Xia, Fan; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [R01 CA073818, R01 CA073818-11, R01 CA073818-12]; NIDDK NIH HHS [R37 DK017776-33, DK17776, P30 DK040561, P30 DK040561-12, P30 DK057521, R37 DK017776, R37 DK017776-34] NR 31 TC 148 Z9 156 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 11 PY 2008 VL 18 IS 5 BP 311 EP 321 DI 10.1016/j.cub.2008.02.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273LL UT WOS:000253932000021 PM 18328708 ER PT J AU Saam, T Underhill, HR Chu, BC Takaya, N Cai, JM Polissar, NL Yuan, C Hatsukami, TS AF Saam, Tobias Underhill, Hunter R. Chu, Baocheng Takaya, Norihide Cai, Jianming Polissar, Nayak L. Yuan, Chun Hatsukami, Thomas S. TI Prevalence of American heart association type VI carotid atherosclerotic lesions identified by magnetic resonance imaging for different levels of stenosis as measured by duplex ultrasound SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RISK-ASSESSMENT STRATEGIES; IN-VIVO; INTRAPLAQUE HEMORRHAGE; VULNERABLE PATIENT; ARTERY STENOSIS; PLAQUE; CLASSIFICATION; ENDARTERECTOMY; MRI; DEFINITIONS AB Objectives Via magnetic resonance imaging (MRI), we sought to determine the prevalence of atherosclerotic American Heart Association type VI lesions (AHA-LT6) (lesions with luminal surface defect, hemorrhage/thrombus, or calcified nodule) in carotid arteries that represented all categories of stenosis as measured by duplex ultrasound. Background Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events. Autopsy studies suggest that features associated with AHA-LT6 lesions, rather than the degree of luminal narrowing, characterize the high-risk plaque. Methods A total of 192 subjects underwent bilateral carotid artery magnetic resonance imaging (MRI) scans at 1.5T after evaluation with ultrasound to determine stenosis. After excluding arteries with a previous endarterectomy, poor image quality, or missing ultrasound data, there were 175 patients with 260 arteries available for analysis. The AHA lesion type was determined by the consensus opinion of 2 experienced carotid MRI reviewers. Results In total, 96 of 260 (37.0%) arteries had >= location with AHA-LT6. Of the arteries with AHA-LT6, 84.4% had hemorrhage, 45.8% had a ruptured fibrous cap, and 14.6% showed other type of complications. Prevalence of AHA-LT6 was an increasing sequence of 8.1% in the 37 arteries with 1% to 15% stenosis, 21.7% in the 60 arteries with 16% to 49% stenosis, 36.8% in the 114 arteries with 50% to 79% stenosis, and 77.6% in the 49 arteries with 80% to 99% stenosis. Conclusions Complicated AHA-LT6 are frequently found in arteries with <= 50% stenosis. These findings indicate that complex lesions develop in a substantial number of arteries in the absence of high-grade stenosis. Ongoing prospective studies will determine the predictive value of vulnerable plaque features, as visualized by MRI, for risk of subsequent ischemic events. C1 [Hatsukami, Thomas S.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Saam, Tobias] Univ Munich, Dept Clin Radiol, Munich, Germany. [Underhill, Hunter R.; Chu, Baocheng; Takaya, Norihide; Cai, Jianming; Yuan, Chun] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. RP Hatsukami, TS (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Surg & Perioperat Care 112,1660 S Columbian Way, Seattle, WA 98195 USA. EM tomhat@u.washington.edu FU NHLBI NIH HHS [T32 HL07828, P01 HL072262, R01 HL073401, R01 HL61851, R01HL56874] NR 24 TC 67 Z9 71 U1 0 U2 5 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 MAR 11 PY 2008 VL 51 IS 10 BP 1014 EP 1021 DI 10.1016/j.jacc.2007.10.054 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JG UT WOS:000253997000007 PM 18325441 ER PT J AU Arnold, SV Morrow, DA Wang, KJ Lei, Y Mahoney, EM Kempf, JA Scirica, BM Cohen, DJ AF Arnold, Suzanne V. Morrow, David A. Wang, Kaijun Lei, Yang Mahoney, Elizabeth M. Kempf, Judith A. Scirica, Benjamin M. Cohen, David J. TI Effects of ranolazine on disease-specific health status and quality of life: Results from the MERLIN-TIMI 36 randomized trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Brigham & Womens Hosp, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A215 EP A215 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101375 ER PT J AU Avelar, E Durst, R Thangaroopan, M Rosilo, GA Tournoux, F Chan, RC Hung, J Hoffmann, U Abbara, S Cury, RC AF Avelar, Erick Durst, Ronen Thangaroopan, Molly Rosilo, Guido A. Tournoux, Francois Chan, Raymond C. Hung, Judy Hoffmann, Udo Abbara, Suhny Cury, Ricardo C. TI Accuracy of multi-detector computed tomography evaluation of left atrial volume for prognostic evaluation: a phantom and echo correlation study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Avelar, Erick; Durst, Ronen; Thangaroopan, Molly; Rosilo, Guido A.; Tournoux, Francois; Chan, Raymond C.; Hung, Judy; Hoffmann, Udo; Abbara, Suhny; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A153 EP A153 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101111 ER PT J AU Baggish, AL Wang, F Weiner, RB Elinott, JM Tournoux, F Boland, A Picard, MH Hutter, AM Wood, MJ AF Baggish, Aaron L. Wang, Francis Weiner, Rory B. Elinott, Jason M. Tournoux, Francois Boland, Arthur Picard, Michael H. Hutter, Adolph M., Jr. Wood, Malissa J. TI Sport-specific changes in cardiac structure and function: A prospective and longitudinal assessment of competitive athletes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Baggish, Aaron L.; Wang, Francis; Weiner, Rory B.; Elinott, Jason M.; Tournoux, Francois; Boland, Arthur; Picard, Michael H.; Hutter, Adolph M., Jr.; Wood, Malissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A372 EP A372 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102501 ER PT J AU Blendea, D Nandigam, V Mela, T Heist, EK McPherson, CA Ruskin, JN Singh, JR AF Blendea, Dan Nandigam, Veena Mela, Theofame Heist, E. Kevin McPherson, Craig A. Ruskin, Jeremy N. Singh, Jagmeet R. TI Variability in the three-dimensional geometry of the coronary sinus: A rotational coronary venous angiography study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Bridgeport Hosp, Dept Cardiol, Bridgeport, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A22 EP A22 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997100094 ER PT J AU Bradley, SM Soine, LA Caldwell, JH Goldberg, SL AF Bradley, Steven M. Soine, Laurie A. Caldwell, James H. Goldberg, Steven L. TI Effect of stress myocardial perfusion imaging results on liver transplant eligibility SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A257 EP A257 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102010 ER PT J AU Chia, S Raffel, OC Merchant, F Senatore, F Jang, IK AF Chia, Stanley Raffel, O. Christopher Merchant, Faisal Senatore, Fred Jang, Ik-Kyung CA EVOLVE Investigators TI Comparison of infarct size and cardiac function in patients with and without diabetes mellitus after primary percutaneous coronary intervention for acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Chia, Stanley; Raffel, O. Christopher; Merchant, Faisal; Senatore, Fred; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A194 EP A194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101290 ER PT J AU Galin, I Trost, B Kang, J Lookstein, R Jaff, MR Abbruzzese, TA Gustavson, S Olin, JW AF Galin, Ira Trost, Biana Kang, Jeanwan Lookstein, Robert Jaff, Michael R. Abbruzzese, Thomas A. Gustavson, Susan Olin, Jeffrey W. TI Validation of renal duplex ultrasound in detecting renal artery stenosis post stenting SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A317 EP A317 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102272 ER PT J AU Hakeem, A Bhatti, S Dillie, K Cook, JR Samad, Z Chang, SM AF Hakeem, Abdul Bhatti, Sabha Dillie, Kathryn Cook, Jeffery R. Samad, Zainab Chang, SuMin TI Abnormal myocardial SPECT is a powerful predictor of cardiac death (CD) in patients with chronic kidney disease (CKD) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Wisconsin, Hosp & Clin, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A167 EP A167 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101172 ER PT J AU Haradsdottir, S Sigurdsson, AF Lehman, S Eyjolfsson, K Gudnason, T Scheving, SS Hoffmann, U Jonsdottir, B Andersen, K AF Haradsdottir, Sigurdis Sigurdsson, Axel F. Lehman, Sam Eyjolfsson, Kristian Gudnason, Thorarinn Scheving, Sigurpall S. Hoffmann, Udo Jonsdottir, Birna Andersen, Karl TI Diagnostic accuracy of 64-slice cardiac computed tomography for detection of in-stent restenosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Landspitati Univ Hosp, Reykjavik, Iceland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A148 EP A148 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101090 ER PT J AU Harkness, JR Scirica, BM Sabatme, MS Morrow, DA Sloan, S Wiviott, SD Giugliano, RP Cannon, CP Braunwald, E AF Harkness, James R. Scirica, Benjamin M. Sabatme, Marc S. Morrow, David A. Sloan, Sarah Wiviott, Stephen D. Giugliano, Robert P. Cannon, Christopher P. Braunwald, Eugene TI Extent of ST segment resolution after fibrinolysis adds dynamic risk stratification to the TIMI risk score for STEMI SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A221 EP A221 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101402 ER PT J AU Haugen, SJ Regensteiner, JG Hiatt, WR Nehler, M Eng, M Rueda, C Strecker, P Bucher-Bartelson, B Casserly, IP AF Haugen, Scott J. Regensteiner, Judith G. Hiatt, William R. Nehler, Mark Eng, Marvin Rueda, Carlos Strecker, Pamela Bucher-Bartelson, Becki Casserly, Ivan P. TI Clinical outcomes in patients with advanced limb ischemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Haugen, Scott J.; Regensteiner, Judith G.; Hiatt, William R.; Nehler, Mark; Eng, Marvin; Rueda, Carlos; Strecker, Pamela; Bucher-Bartelson, Becki; Casserly, Ivan P.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A337 EP A337 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102353 ER PT J AU Ho, PM Peterson, ED Wang, L Magid, DJ Fihn, SD Larsen, GC Jesse, RA Rumsfeld, JS AF Ho, P. Michael Peterson, Eric D. Wang, Li Magid, David J. Fihn, Stephan D. Larsen, Greg C. Jesse, Robert A. Rumsfeld, John S. TI Incidence of death and myocardial infarction associated with stopping clopidogrel after acute coronary syndrome: Evidence supporting a rebound effect SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Ho, P. Michael; Peterson, Eric D.; Wang, Li; Magid, David J.; Fihn, Stephan D.; Larsen, Greg C.; Jesse, Robert A.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Ho, P. Michael; Peterson, Eric D.; Wang, Li; Magid, David J.; Fihn, Stephan D.; Larsen, Greg C.; Jesse, Robert A.; Rumsfeld, John S.] Univ Colorado Hlth Sci Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A250 EP A250 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101521 ER PT J AU Hsieh, BPC Whooley, MA Schiller, NB AF Hsieh, Bill Pei-Chin Whooley, Mary A. Schiller, Nelson B. TI The prevalence and prognostic value of cardiac troponin T elevation in ambulatory patients with stable coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A378 EP A378 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102522 ER PT J AU Lehman, SJ Hsu, J Abbara, S Cury, R Goela, A Dodd, J Bamberg, F Schlett, C Nagurney, JT Brady, TJ Hoffmann, U AF Lehman, Sam J. Hsu, Joe Abbara, Suhny Cury, Ricardo Goela, Aashish Dodd, Jonathan Bamberg, Fabian Schlett, Christopher Nagurney, John T. Brady, Thomas J. Hoffmann, Udo TI Prevalence and nature of non-cardiac incidental findings and their effect on patient management and subsequent diagnostic testing in patients with acute chest pain undergoing cardiac computed tomography: The ROMICAT study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Lehman, Sam J.; Hsu, Joe; Abbara, Suhny; Cury, Ricardo; Goela, Aashish; Dodd, Jonathan; Bamberg, Fabian; Schlett, Christopher; Nagurney, John T.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A146 EP A147 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101085 ER PT J AU Lehman, SJ Bamberg, F Schlett, C Abbara, S Cury, R Rogers, AS Shturman, L Brady, TJ Hoffmann, U AF Lehman, Sam J. Bamberg, Fabian Schlett, Christopher Abbara, Suhny Cury, Ricardo Rogers, An S. Shturman, Leon Brady, Thomas J. Hoffmann, Udo TI Progression of coronary artery disease after two-year follow-up in patients with acute chest pain: The ROMICAT follow-up study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Lehman, Sam J.; Bamberg, Fabian; Schlett, Christopher; Abbara, Suhny; Cury, Ricardo; Rogers, An S.; Shturman, Leon; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A146 EP A146 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101082 ER PT J AU Maddox, TM Ross, C He, PM Masoudi, FA Magid, D Daugherty, S Peterson, P Rumsfeld, JS AF Maddox, Thomas M. Ross, Colleen He, P. Michael Masoudi, Fred A. Magid, David Daugherty, Stacie Peterson, Pam Rumsfeld, John S. TI The prognostic importance of impaired heart rate recovery and chronotropic incompetence in association with the duke treadmill score during exercise stress testing SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Colorado, Hlth Sci Ctr, Denver VAMC, Denver, CO 80202 USA. Kaiser Permanente, Denver, CO USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 MAR 11 PY 2008 VL 51 IS 10 SU A BP A160 EP A160 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101140 ER PT J AU Marlinez-Rumayor, AA Green, SM Baggish, AL O'Donoghue, M Januzzi, JL AF Marlinez-Rumayor, Abelardo A. Green, Sandy M. Baggish, Aaron L. O'Donoghue, Michelle Januzzi, James L. TI Soluble ST2 plasma concentrations predict mortality in dyspneic patients with pulmonary disease: Results from the ProBNP investigation of dyspnea in the emergency department (PRIDE) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Marlinez-Rumayor, Abelardo A.; Green, Sandy M.; Baggish, Aaron L.; O'Donoghue, Michelle; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A362 EP A362 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102457 ER PT J AU Nasir, K Rivera, JJ Yoon, Y Choi, EK Choi, SI Oh, B Blumenthal, RS Chang, HJ AF Nasir, Khurram Rivera, Juan J. Yoon, Yeonyee Choi, Eue-Keun Choi, Sang-Il Oh, Byunghee Blumenthal, Roger S. Chang, Hyuk-Jae TI A higher Coronary Artery Calcium Score is associated with a greater mixed and heterogeneous plaque burden on coronary computed tomography angiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Nasir, Khurram; Rivera, Juan J.; Yoon, Yeonyee; Choi, Eue-Keun; Choi, Sang-Il; Oh, Byunghee; Blumenthal, Roger S.; Chang, Hyuk-Jae] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI PET CT Program, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A155 EP A155 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101119 ER PT J AU O'Donoghue, M Boden, WE Cannon, CP Clayton, TC de Winter, RJC Fox, KAA Lagerqvist, B McCullough, PA Murphy, SA Spacek, R Swann, E Wallentin, L Windhausen, F Sabatine, MS AF O'Donoghue, Michelle Boden, William E. Cannon, Christopher P. Clayton, Tim C. de Winter, Robbert J. Fox, Keith A. A. Lagerqvist, Bo McCullough, Peter A. Murphy, Sabina A. Spacek, Rudolf Swann, Eva Wallentin, Lars Windhausen, Forts Sabatine, Marc S. TI The benefit of an invasive strategy in diabetic versus non-diabetic subjects with Non-ST-Elevation acute coronary syndromes: A collaborative meta-analysis of randomized trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A216 EP A216 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101378 ER PT J AU Patel, DN Erikson, JM Bailey, SR Valente, AJ Chandrasekar, B AF Patel, Devanci N. Erikson, John M. Bailey, Steven R. Valente, Anthony J. Chandrasekar, Bysani TI Adiponectin blocks IL-18-mediated endothelial cell death through activation of Akt and suppression of NF42B-PTEN signaling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A298 EP A298 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102189 ER PT J AU Poh, KK Tournoux, FB Picard, MH Wood, MJ AF Poh, Kian Keong Tournoux, Francios B. Picard, Michael H. Wood, Malissa J. TI Left ventricular performance and its determinants immediately prior to and post-marathon running: Insights from two dimensional speckle tracking echocardiography and serum biomarkers SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A174 EP A174 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101202 ER PT J AU Rogers, IS Nasir, K Figueroa, AL Vermylen, DA Cury, RC Hoffmann, U Brady, TJ Tawakol, A AF Rogers, Ian S. Nasir, Khurram Figueroa, Amparo L. Vermylen, David A. Cury, Ricardo C. Hoffmann, Udo Brady, Thomas J. Tawakol, Ahmed TI Inflammation in coronary plaques detected by combined 18-fluorodeoxyglucose positron emission tomography and 64-slice multidetector computed tomography imaging correlates with circulating biomarkers of inflammation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A169 EP A169 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101182 ER PT J AU Salemi, VM Rochitte, CE Shiozaki, AA Andrade, JM Parga, JR Avila, LF Oliveira, SA Benvenuti, LA Cestari, IN Picard, MH AF Salemi, Vera M. Rochitte, Carlos E. Shiozaki, Afonso A. Andrade, Joalbo M. Parga, Jose R. Avila, Luiz F. Oliveira, Sergio A. Benvenuti, Luiz A. Cestari, Ismar N. Picard, Michael H. TI Delayed enhancement magnetic resonance imaging in the diagnosis and prognosis of endomyocardial fibrosis patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Cestari, Ismar /B-7286-2012; Benvenuti, Luiz/C-6614-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A164 EP A164 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101159 ER PT J AU Sarwar, AB Nasir, K Gopal, A Kalia, N Orakzai, R Blumenthal, RS Budoff, MJ AF Sarwar, Ahmed B. Nasir, Khurram Gopal, Ambarish Kalia, Nove Orakzai, Raza Blumenthal, Roger S. Budoff, Matthew J. TI Adherence to lipid lowering medication among individuals with a coronary artery calcium score greater than 400 is associated with slower progression of atherosclerosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Sarwar, Ahmed B.; Nasir, Khurram; Gopal, Ambarish; Kalia, Nove; Orakzai, Raza; Blumenthal, Roger S.; Budoff, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A153 EP A153 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101112 ER PT J AU Sarwar, A Shaw, LJ Sarwar, AB Rumberger, J Berman, DS Callister, TQ Raggi, P Hoffmann, U Budoff, MJ Blumenthal, RS Nasir, K AF Sarwar, Ammar Shaw, Leslee J. Sarwar, Ahmad B. Rumberger, John Berman, Daniel S. Callister, Tracy Q. Raggi, Paolo Hoffmann, Udo Budoff, Matthew J. Blumenthal, Roger S. Nasir, Khurram TI Predictors of all cause mortality in subjects without evidence of coronary artery calcification SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Sarwar, Ammar; Shaw, Leslee J.; Sarwar, Ahmad B.; Rumberger, John; Berman, Daniel S.; Callister, Tracy Q.; Raggi, Paolo; Hoffmann, Udo; Budoff, Matthew J.; Blumenthal, Roger S.; Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A155 EP A155 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101118 ER PT J AU Scirica, BM Sabatine, MS Jarolim, P Sloan, S Murphy, SA De Lemos, JL Morrow, DA AF Scirica, Beniamin M. Sabatine, Marc S. Jarolim, Petr Sloan, Sarah Murphy, Sabina A. De Lemos, James L. Morrow, David A. TI Myeloperoxidase levels associated with risk of cardiovascular death and heart failure after non-ST elevation acute coronary syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A218 EP A218 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997101387 ER PT J AU Truong, QA Sarwar, A Cannon, CP Nasir, K Handschumacher, M Kalra, M Sorgente, A Conca, C Faletra, F Auricchio, A Moccetti, T Singh, JP Hoffmann, U AF Truong, Quynh A. Sarwar, Ammar Cannon, Christopher P. Nasir, Khurram Handschumacher, Mark Kalra, Mannudeep Sorgente, Antonio Conca, Cristina Faletra, Francesco Auricchio, Angelo Moccetti, Tiziano Singh, Jagmeet P. Hoffmann, Udo TI Novel method for assessing intraventricular dyssynchrony using quantitative analysis of regional wall thickness by multi-detector computed tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cardioctr Ticino, Lugano, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A20 EP A20 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997100085 ER PT J AU Zabalgoitia, MR Chilton, R Moody, JM Bailey, SR Chandrasekar, B AF Zabalgoitia, Miguel R. Chilton, Robert Moody, Joe M., Jr. Bailey, Steven R. Chandrasekar, Bysani TI High glucose and advanced glycation end products potentiate IL-17-mediated human coronary artery smooth muscle cell proliferation, and is reversed by resveratrol SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A283 EP A283 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102122 ER PT J AU Zenovich, AG Nelson, WD Panoskaltsis-Mortari, A Caron, GJ Ott, H Taylor, DA AF Zenovich, Andrey G. Nelson, Wendy D. Panoskaltsis-Mortari, Angela Caron, Gabriel J. Ott, Harald Taylor, Doris A. TI Sex-based differences in bone marrow progenitor cell depletion and immune response of atherosclerosis: Viewing atherosclerosis as a disease of failed endogenous SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Univ Minnesota, Minneapolis, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU A BP A293 EP A294 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JH UT WOS:000253997102170 ER PT J AU Fernandez-Pereira, C Mieres, J Risau, G Santaera, O Rodriguez-Granillo, AM Rodriguez-Granillo, GA Mauree, AO Palacios, IF Rodriquez, AE AF Fernandez-Pereira, Carlos Mieres, Juan Risau, Gustavo Santaera, Omar Rodriguez-Granillo, Alfredo M. Rodriguez-Granillo, Gaston A. Mauree, Andrew O. Palacios, Igor F. Rodriquez, Alfredo E. TI Bare metal stents plus oral rapamycin are more cost effective than drug eluting stents in patients undergoing PCI for de novo coronary lesions: Insights from the randomized,controlled ORAR III study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Santario Otamendi, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU B BP B88 EP B88 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JI UT WOS:000253997200372 ER PT J AU Finn, AV Oh, J Daher, M Byrne, RM Byrne, RM Palacios, I John, MC Gold, HK AF Finn, Aloke V. Oh, Jae Daher, Maureen Byrne, Rafael M. Byrne, Rafael M. Palacios, Igor John, Michael C. Gold, Herman K. TI Vascular complications and time to ambulation in patients undergoing PCI with heparin & glycoprotein IIB/IIIA versus bivalirudin SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Finn, Aloke V.; Oh, Jae; Daher, Maureen; Byrne, Rafael M.; Byrne, Rafael M.; Palacios, Igor; John, Michael C.; Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU B BP B96 EP B96 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JI UT WOS:000253997200407 ER PT J AU Jneid, H Cruz-Gonzalez, I Sanchez-Ledesman, M Otero, JP Vigo, S Cubeddu, RJ Maree, AO Palacios, IF AF Jneid, Hani Cruz-Gonzalez, Ignacio Sanchez-Ledesman, Maria Otero, Juan Pal Vigo, Santiago Cubeddu, Roberto J. Maree, Andrew O. Palacios, Igor F. TI Gender differences in procedural and clinical outcomes after percutaenous balloon mitral valvuloplasty SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 [Jneid, Hani; Cruz-Gonzalez, Ignacio; Sanchez-Ledesman, Maria; Otero, Juan Pal; Vigo, Santiago; Cubeddu, Roberto J.; Maree, Andrew O.; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU B BP B80 EP B80 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JI UT WOS:000253997200338 ER PT J AU John, MC Crimins, J Lajoie, S Gold, HK Wight, TN Finn, AV AF John, Michael C. Crimins, Johanna Lajoie, Scott Gold, Herman K. Wight, Thomas N. Finn, Aloka V. TI Insulin resistance alters neointimal extracellular matrix composition after arterial injury: Role of versican SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Emory Crawford Long Hosp, Dept Internal Med, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 11 PY 2008 VL 51 IS 10 SU B BP B93 EP B93 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274JI UT WOS:000253997200393 ER PT J AU Flaherty, AW AF Flaherty, Alice W. TI Playing doctor well SO NEUROLOGY LA English DT Editorial Material C1 [Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Flaherty, Alice W.] Harvard Univ, Sch Med, Boston, MA USA. RP Flaherty, AW (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 729B,15 Parkman St, Boston, MA 02114 USA. EM aflaherty@partners.org NR 11 TC 1 Z9 1 U1 1 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 MAR 11 PY 2008 VL 70 IS 11 BP 826 EP 827 DI 10.1212/01.wnl.0000304744.73977.a2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 271WU UT WOS:000253820200002 PM 18332340 ER PT J AU Carlson, NE Moore, MM Dame, A Howieson, D Silbert, LC Quinn, JF Kaye, JA AF Carlson, N. E. Moore, M. M. Dame, A. Howieson, D. Silbert, L. C. Quinn, J. F. Kaye, J. A. TI Trajectories of brain loss in aging and the development of cognitive impairment SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; TEMPORAL-LOBE; VOLUME LOSS; OLDEST-OLD; ATROPHY; HIPPOCAMPUS; DEMENTIA; DECLINE; RATES; MCI AB Background: The use of volumetric MRI as a biomarker for assessing transitions to dementia presumes that more rapid brain loss marks the clinical transition from benign aging to mild cognitive impairment (MCI). The trajectory of this volume loss relative to the timing of the clinical transition to dementia has not been established. Methods: The authors annually evaluated 79 healthy elderly subjects for up to 15 consecutive years with standardized clinical examinations and volumetric brain MRI assessments of ventricular volume. During the study period, 37 subjects developed MCI. A mixed effects model with a change point modeled the pattern of brain volume loss in healthy aging compared with subjects diagnosed with MCI. Results: The brain loss trajectory of subjects developing MCI during follow-up differed from healthy aging in a two-phase process. First, the annual rate of expansion of ventricular volume decreased with age; however, the annual rates of expansion were greater in those who developed cognitive impairment during follow-up compared with those who did not. Further, subjects who developed MCI had an acceleration of ventricular volume expansion approximately 2.3 years prior to clinical diagnosis of MCI. Conclusions: Ventricular expansion is faster in those developing mild cognitive impairment years prior to clinical symptoms, and eventually a more rapid expansion occurs approximately 24 months prior to the emergence of clinical symptoms. These differential rates of preclinical atrophy suggest that there are specific windows for optimal timing of introduction of dementia prevention therapies in the future. C1 [Carlson, N. E.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97239 USA. [Moore, M. M.; Dame, A.; Howieson, D.; Silbert, L. C.; Quinn, J. F.; Kaye, J. A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kaye, J. A.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. [Silbert, L. C.; Quinn, J. F.] Portland VA Med Ctr, Portland, OR USA. RP Carlson, NE (reprint author), Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, 3181 SW Sam Jackson Pk Rd,Mail Code CB669, Portland, OR 97239 USA. EM carlsoni@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [UL1 RR024140 01]; NIA NIH HHS [AG08017] NR 27 TC 80 Z9 82 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 11 PY 2008 VL 70 IS 11 BP 828 EP 833 DI 10.1212/01.wnl.0000280577.43413.d9 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 271WU UT WOS:000253820200003 PM 18046010 ER PT J AU Catana, C Procissi, D Wu, YB Judenhofer, MS Qi, JY Pichler, BJ Jacobs, RE Cherry, SR AF Catana, Ciprian Procissi, Daniel Wu, Yibao Judenhofer, Martin S. Qi, Jinyi Pichler, Bernd J. Jacobs, Russell E. Cherry, Simon R. TI Simultaneous in vivo positron emission tomography and magnetic resonance imaging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE molecular imaging; small animal imaging; multimodality imaging ID HUMAN BRAIN; CONTRAST AGENTS; MRI; CANCER; PET; RESOLUTION; REGISTRATION; SPECTROSCOPY; IMAGES AB Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner. C1 [Catana, Ciprian; Wu, Yibao; Qi, Jinyi; Cherry, Simon R.] Univ Calif Davis, Dept Biomed Engn, Genome & Biomed Sci Facil, Davis, CA 95616 USA. [Procissi, Daniel; Jacobs, Russell E.] CALTECH, Beckman Inst, Pasadena, CA 91125 USA. [Judenhofer, Martin S.; Pichler, Bernd J.] Univ Tubingen, Lab Preclin Imaging & Imaging Technol, Dept Radiol, D-72076 Tubingen, Germany. RP Catana, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM ccatana@nmr.mgh.harvard.edu RI Qi, Jinyi/A-1768-2010; Judenhofer, Martin/C-5274-2011; Pichler, Bernd/B-4483-2012 OI Qi, Jinyi/0000-0002-5428-0322; Judenhofer, Martin/0000-0001-6886-0021; FU NCRR NIH HHS [U24 RR021760]; NIBIB NIH HHS [R01 EB000194-01A1, R01 EB000194, R01 EB000194-02, R01 EB000194-03, R01 EB000194-04, R01 EB000194-05, R01 EB000993, R01 EB00194, R01 EB00993]; NINDS NIH HHS [R43 NS055377] NR 36 TC 173 Z9 174 U1 2 U2 26 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 MAR 11 PY 2008 VL 105 IS 10 BP 3705 EP 3710 DI 10.1073/pnas.0711622105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273KZ UT WOS:000253930600010 PM 18319342 ER PT J AU Grotenbreg, GM Roan, NR Guillen, E Meijers, R Wang, JH Bell, GW Starnbach, MN Ploegh, HL AF Grotenbreg, Gijsbert M. Roan, Nadia R. Guillen, Eduardo Meijers, Rob Wang, Jia-huai Bell, George W. Starnbach, Michael N. Ploegh, Hidde L. TI Discovery of CD8(+) T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE conditional ligands; crystal structure; consensus epitope prediction ID CRYSTAL-STRUCTURES; ESCHERICHIA-COLI; PEPTIDE; COMPLEX; LYMPHOCYTES; MOLECULES; VIRUS; BIOTINYLATION; GENERATION; RESOLUTION AB Class I MHC tetramers allow direct phenotypic identification of CD8(+) T cell populations, but their production remains laborious. A peptide exchange strategy that employs class I MHC products loaded with conditional ligands (caged MHC molecules) provides a fast and straightforward method to obtain diverse arrays of class I MHC tetramers and facilitates CD8(+) T cell epitope discovery. Here, we describe the development of photocleavable analogs of the FAPGNYPAL (SV9) epitope that bind H-2K(b) and H-2D(b) with full retention of their structural and functional integrity. We ranked all possible H-2Kb octameric and H-2D(b) nonameric epitopes that span the genome of Chlamydia trachomatis and prepared MHC tetramers from approximate to 2,000 of the highest scoring peptides by replacement of the SV9 analog with the peptide of choice. The resulting 2,000-member class I MHC tetramer array allowed the discovery of two variants of an epitope derived from polymorphic membrane protein I (PmpI) and an assessment of the kinetics of emergence and the effector function of the corresponding CD8(+) T cells. C1 [Grotenbreg, Gijsbert M.; Guillen, Eduardo; Meijers, Rob; Wang, Jia-huai; Bell, George W.; Ploegh, Hidde L.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. [Roan, Nadia R.; Starnbach, Michael N.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Meijers, Rob] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Meijers, Rob; Wang, Jia-huai] Dana Farber Canc Inst, Dept Med Oncol, Immunol Lab, Boston, MA 02115 USA. RP Ploegh, HL (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02139 USA. EM ploegh@wi.mit.edu RI Meijers, Rob/D-5521-2011; OI Meijers, Rob/0000-0003-2872-6279 NR 41 TC 52 Z9 54 U1 0 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 MAR 11 PY 2008 VL 105 IS 10 BP 3831 EP 3836 DI 10.1073/pnas.0711504105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273KZ UT WOS:000253930600033 PM 18245382 ER PT J AU Perlot, T Li, G Alt, FW AF Perlot, Thomas Li, Gang Alt, Frederick W. TI Antisense transcripts from immunoglobulin heavy-chain locus V(D)J and switch regions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE class switch recombination; somatic hypermutation; activation-induced cytosine deaminase; bidirectional transcription ID SINGLE-STRANDED-DNA; CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; INTERGENIC TRANSCRIPTION; ANTIBODY DIVERSIFICATION; GENE-EXPRESSION; CELL-LINES; B-CELLS; R-LOOPS; C-MYC AB Activation-induced cytosine deaminase (AID) is essential for both somatic hypermutation (SHM) and class switch recombination (CSR), two processes involved in antibody diversification. Previously, various groups showed both in vitro and in vivo that AID initiates SHIM and CSR by deaminating cytosines in DNA in a transcription-dependent manner. Although in vivo both DNA strands are equally targeted by AID, many in vitro and bacterial experiments found that AID almost exclusively targets the non-template strand of a transcribed substrate. Here, we report the detection of antisense transcripts in assembled 19 heavy chain (IgH) variable region exons and their immediate downstream region, as well as in switch regions, sequences that, respectively, are targets for SHM and CSR in vivo. In contrast, we did not detect antisense transcripts from the C mu constant region exons, which lie between the IgH variable region exons and downstream S regions and which are not normally an AID target. Expression of the antisense variable region/flanking region and the S-region transcripts were found in all lymphocytes that transcribe these sequences in the sense direction. Steady-state levels of antisense transcripts appeared very low, and start sites potentially appeared heterogeneous. We discuss the potential implications of antisense IgH locus transcription for AID targeting or other processes. C1 [Perlot, Thomas; Li, Gang; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. [Perlot, Thomas; Li, Gang; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Perlot, Thomas] Univ Vienna, A-1010 Vienna, Austria. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst,Howard Hughes Med Inst, 1 Blackfan Circle, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA092625, P01CA092625-05]; NIAID NIH HHS [2P01AI031541-15, P01 AI031541] NR 46 TC 36 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 11 PY 2008 VL 105 IS 10 BP 3843 EP 3848 DI 10.1073/pnas.0712291105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273KZ UT WOS:000253930600035 PM 18292225 ER PT J AU Daugherty, SL Ho, PM Spertus, JA Jones, PG Bach, RG Krumholz, HM Peterson, ED Rumsfeld, JS Masoudi, FA AF Daugherty, Stacie L. Ho, P. Michael Spertus, John A. Jones, Philip G. Bach, Richard G. Krumholz, Harlan M. Peterson, Eric D. Rumsfeld, John S. Masoudi, Frederick A. TI Association of early follow-up after acute myocardial infarction with higher rates of medication use SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs ID SECONDARY PREVENTION; CARE TRANSITIONS; ELDERLY PATIENTS; CORONARY; ADHERENCE; DISEASE; PREVALENCE; GUIDELINES; SPECIALTY; DISCHARGE AB Background: Early outpatient follow-up after acute myocardial infarction (AMI) is recommended in guidelines, but its relationship with the use of evidence-based therapies is unknown. Methods: We evaluated 1516 patients hospitalized with AMI from the multicenter Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery registry. Early follow-up was defined as patient-reported visits with a primary care physician or cardiologist within 1 month after discharge. The primary outcomes were use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and statins in eligible patients at 6 months. Multivariable analyses assessed the association between early follow-up and medication use at 6 months, adjusting for patient and clinical characteristics. Secondary analyses compared medication use at 6 months for patients receiving collaborative follow-up from a single provider vs those receiving follow-up from both provider types. Results: Among the cohort, 34% reported no outpatient follow-up during the month following discharge. Rates of medication prescription among appropriate candidates were similar at hospital discharge for both follow-up groups. Compared with those not receiving early follow-up, those receiving early follow-up were more likely to be prescribed beta-blockers (80.1% vs 71.3%; P = .001), aspirin (82.9% vs 77.1%; P = .01), or statins (75.9% vs 68.6%; P = .005) at 6 months. In multivariable analyses, a persistent relationship remained between early followup and beta-blocker use (risk ratio, 1.08; 95% confidence interval, 1.02-1.15). In secondary analyses, statin use was higher in patients receiving collaborative follow-up (risk ratio, 1.11; 95% confidence interval, 1.01-1.22). Conclusions: Early outpatient follow-up and collaborative follow-up after AMI is associated with higher rates of evidence-based medication use. Although further studies should assess whether this relationship is causal, these results support current guideline recommendations for follow-up after AMI. C1 [Daugherty, Stacie L.; Ho, P. Michael; Rumsfeld, John S.; Masoudi, Frederick A.] Univ Colorado, Denver Hlth Sci Ctr, Div Cardiol, Dept Med, Aurora, CO 80045 USA. [Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Kansas City, MO USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Bach, Richard G.] Washington Univ, Med Ctr, St Louis, MO USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. [Peterson, Eric D.] Duke Univ, Sch Med, Durham, NC USA. [Spertus, John A.; Jones, Philip G.] Denver Hlth Med Ctr, Kansas City, MO USA. [Spertus, John A.; Jones, Philip G.] Mid Amer Heart Inst, Kansas City, MO USA. RP Daugherty, SL (reprint author), Univ Colorado, Denver Hlth Sci Ctr, Div Cardiol, Dept Med, 12631 E 17th Ave,Mail Stop B130,POB 6511, Aurora, CO 80045 USA. EM stacie.daugherty@uchsc.edu NR 25 TC 40 Z9 40 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 10 PY 2008 VL 168 IS 5 BP 485 EP 491 DI 10.1001/archinte.168.5.485 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 272SZ UT WOS:000253881400007 PM 18332293 ER PT J AU Jagsi, R Weinstein, DF Shapiro, J Kitch, BT Dorer, D Weissman, JS AF Jagsi, Reshma Weinstein, Debra F. Shapiro, Jo Kitch, Barrett T. Dorer, David Weissman, Joel S. TI The Accreditation Council for Graduate Medical Education's limits on residents' work hours and patient safety SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DUTY HOURS; ADVERSE EVENTS; HOUSE STAFF; NATIONAL-SURVEY; INTENSIVE-CARE; IMPACT; ERRORS; PERCEPTIONS; OUTCOMES; QUALITY AB Background: Limiting resident work hours may improve patient safety, but unintended adverse effects are also possible. We sought to assess the impact of Accreditation Council for Graduate Medical Education resident work hour limits implemented on July 1, 2003, on resident experiences and perceptions regarding patient safety. Methods: All trainees in 76 accredited programs at 2 teaching hospitals were surveyed in 2003 (preimplementation) and 2004 (postimplementation) regarding their work hours and patient load; perceived relation of work hours, patient load, and fatigue to patient safety; and experiences with adverse events and medical errors. Based on reported weekly duty hours, 13 programs experiencing substantial hours reductions were classified into a " reduced-hours" group. Change scores in outcome measures before and after policy implementation in the reduced-hours programs were compared with those in "other programs" to control for temporal trends, using 2-way analysis of variance with interaction. Results: A total of 1770 responses were obtained (response rate, 60.0%). Analysis was restricted to 1498 responses from respondents in clinical years of training. Residents in the reduced-hours group reported significant reductions in mean weekly duty hours (from 76.6 to 68.0 hours, P < .001), and the percentage working more than 80 hours per week decreased from 44.0% to 16.6% (P < .001). No significant increases in patient load while on call (patients admitted, covered, or cross covered) were observed. Between 2003 and 2004, there was a decrease in the proportion of residents in the reduced-hours programs indicating that working too many hours (63.2% vs 44.0%; P < .001) or cross covering too many patients (65.9% vs 46.9%; P = .001) contributed to mistakes in patient care. There were no significant reductions in these 2 measures in the other group, and the differences in differences were significant (P = .03 and P = .02, respectively). The number of residents in reduced-hours programs who reported committing at least 1 medical error within the past week remained high in both study years (32.9% in 2003 and 26.3% in 2004, P = .27). Conclusions: It is possible to reduce residents' hours without increasing patient load. Doing so may reduce the extent to which fatigue affects patient safety as perceived by these frontline providers. C1 [Jagsi, Reshma] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Weinstein, Debra F.; Shapiro, Jo] Partners Hlth Care System, Off Grad Med Educ, Boston, MA USA. [Weinstein, Debra F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Dorer, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. [Kitch, Barrett T.; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. RP Jagsi, R (reprint author), Univ Michigan, Dept Radiat Oncol, UHB2C490,SPC 5010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM reshma_jagsi@post.harvard.edu OI Jagsi, Reshma/0000-0001-6562-1228 NR 43 TC 47 Z9 48 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 10 PY 2008 VL 168 IS 5 BP 493 EP 500 DI 10.1001/archinternmed.2007.129 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 272SZ UT WOS:000253881400009 PM 18332295 ER PT J AU Williams, BA Lindquist, K Sudore, RL Covinsky, KE Walter, LC AF Williams, Brie A. Lindquist, Karla Sudore, Rebecca L. Covinsky, Kenneth E. Walter, Louise C. TI Screening mammography in older women - Effect of wealth and prognosis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ELDERLY-WOMEN; HEALTH-STATUS; SOCIOECONOMIC-STATUS; PREVENTIVE SERVICES; BREAST-CANCER; MEDICARE BENEFICIARIES; CERVICAL-CANCER; UNITED-STATES; SELF-REPORT; MORTALITY AB Background: Wealthy women have higher rates of screening mammography than poor women do. Screening mammography is beneficial for women with substantial life expectancies, but women with limited life expectancies are unlikely to benefit. It is unknown whether higher screening rates in wealthy women are due to increased screening in women with substantial life expectancies, limited life expectancies, or both. This study examines the relationship between wealth and screening mammography use in older women according to life expectancy. Methods: A cohort study was performed of 4222 women 65 years or older with Medicare participating in the 2002 and 2004 Health and Retirement Survey. Women were categorized according to wealth and life expectancy (based on 5-year prognosis from a validated prognostic index). The outcome was self-reported receipt of screening mammography within 2 years. Results: Overall, within 2 years, 68% of women (2871 of 4222) received a screening mammogram. Screening was associated with wealth (net worth, > $100 000) and good prognosis (<= 10% probability of dying in 5 years). Screening mammography was more common among wealthy women than among poor women (net worth, > $10 000) both for women with good prognosis (82% vs 68%; P < .001) and for women with limited prognoses (>= 50% probability of dying in 5 years) (48% vs 32%; P = .02). These associations remained after multivariate analysis accounting for age, race, education, proxy report, and rural residence. Conclusions: Poorer older women with favorable prognoses are at risk of not receiving screening mammography when they are likely to benefit. Wealthier older women with limited prognoses are often screened when they are unlikely to benefit. C1 [Williams, Brie A.; Sudore, Rebecca L.; Covinsky, Kenneth E.; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. [Williams, Brie A.; Lindquist, Karla; Sudore, Rebecca L.; Covinsky, Kenneth E.; Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Williams, BA (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Campus Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu FU NIA NIH HHS [T32-AG00212, R01-AG023626] NR 49 TC 22 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 10 PY 2008 VL 168 IS 5 BP 514 EP 520 DI 10.1001/archinternmed.2007.103 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 272SZ UT WOS:000253881400012 PM 18332298 ER PT J AU Mayer, EL Burstein, HJ AF Mayer, Erica L. Burstein, Harold J. TI Weighing a dose-dense option for adjuvant chemotherapy and trastuzumab in early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TRIAL COMPARING DOXORUBICIN; RANDOMIZED-TRIAL; THERAPY; PACLITAXEL C1 [Mayer, Erica L.; Burstein, Harold J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, EL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 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 MAR 10 PY 2008 VL 26 IS 8 BP 1198 EP 1200 DI 10.1200/JCO.2007.14.8734 PG 3 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300003 PM 18323544 ER PT J AU Perez, EA Suman, VJ Davidson, NE Sledge, GW Kaufman, PA Hudis, CA Martino, S Gralow, JR Dakhil, SR Ingle, JN Winer, EP Gelmon, KA Gersh, BJ Jaffe, AS Rodeheffer, RJ AF Perez, Edith A. Suman, Vera J. Davidson, Nancy E. Sledge, George W. Kaufman, Peter A. Hudis, Clifford A. Martino, Silvana Gralow, Julie R. Dakhil, Shaker R. Ingle, James N. Winer, Eric P. Gelmon, Karen A. Gersh, Bernard J. Jaffe, Allan S. Rodeheffer, Richard J. TI Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the north central cancer treatment group n9831 adjuvant breast cancer trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID CHEMOTHERAPY; CARDIOTOXICITY; DYSFUNCTION; PLUS; HER2; AMPLIFICATION; ONCOGENE; THERAPY AB Purpose To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab then trastuzumab alone (arm C). Left ventricular ejection fraction (LVEF) was evaluated at registration and 3, 6, 9, and 18 to 21 months. Results Of 2,992 patients completing AC, 5.0% had LVEF decreases disallowing trastuzumab (decrease below normal: 2.4%, decrease > 15%: 2.6%). There were 1,944 patients with satisfactory or no LVEF evaluation who proceeded to post-AC therapy. Cardiac events (congestive heart failure [CHF] or cardiac death [CD]): arm A, n = 3 (2 CHF, 1 CD); arm B, n = 19 (18 CHF, 1 CD); arm C, n = 19 (all CHF); 3-year cumulative incidence: 0.3%, 2.8%, and 3.3%, respectively. Cardiac function improved in most CHF cases following trastuzumab discontinuation and cardiac medication. Factors associated with increased risk of a cardiac event in arms B and C: older age (P < .003), prior/current antihypertensive agents (P = .005), and lower registration LVEF (P = .033). Incidence of asymptomatic LVEF decreases requiring holding trastuzumab was 8% to 10%; LVEF recovered and trastuzumab was restarted in approximately 50%. Conclusion The cumulative incidence of post-AC cardiac events at 3 years was higher in the trastuzumab-containing arms versus the control arm, but by less than 4%. Older age, lower registration LVEF, and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC. C1 [Perez, Edith A.] Mayo Clin, Div Hematol Oncol, Jacksonville, FL 32224 USA. Mayo Clin, Rochester, MN USA. Kimmel Canc Ctr Johns Hopkins, Baltimore, MD USA. Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Inst Canc Res, Med Grp, Santa Monica, CA USA. Univ Washington, Seattle, WA 98195 USA. Canc Ctr Kansas, Wichita, KS USA. Dana Farber Canc Inst, Boston, MA USA. Canc Agcy, Vancouver, BC, Canada. RP Perez, EA (reprint author), Mayo Clin, Div Hematol Oncol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM perez.edith@mayo.edu FU NCI NIH HHS [CA25224, U10 CA025224] NR 23 TC 275 Z9 280 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2008 VL 26 IS 8 BP 1231 EP 1238 DI 10.1200/JCO.2007.13.5467 PG 8 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300010 PM 18250349 ER PT J AU Casarett, D Fishman, J O'Dwyer, PJ Barg, FK Naylor, M Asch, DA AF Casarett, David Fishman, Jessica O'Dwyer, Peter J. Barg, Frances K. Naylor, Mary Asch, David A. TI How should we design supportive cancer care? The patient's perspective SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TERMINALLY-ILL PATIENTS; CONJOINT-ANALYSIS; HOSPICE ENROLLMENT; LUNG-CANCER; HEALTH-CARE; PREFERENCES; CAREGIVERS; FAMILIES; NEEDS; PREVALENCE AB Purpose Hospice services are designed to meet the needs of patients near the end of life. Although so-called open-access hospice programs and bridge programs are beginning to offer these services to patients who are still receiving treatment, it is not known whether they best meet patients' needs. Patients and Methods Three hundred adult patients receiving treatment for cancer completed interviews in which each patient's value or ability for supportive care services were calculated from the choices that they made among combinations of those services. Preferences for five traditional hospice services and six alternative supportive care services were measured, and patients were followed up for 6 months or until death. Results Patients' utilities for alternative services were higher than those for traditional hospice services (0.53 v 0.39; sign-rank test P < .001). Alternative services were also preferred among patients with poor functional status (Eastern Cooperative Oncology Group performance score > 2; n = 54; 0.65 v 0.48; P < .001) and among those who were in the last 6 months of life (0.68 v 0.56; sign-rank test P = .003). Even patients who were willing to forgo cancer treatment (n = 38; 13%) preferred alternative services (3.1 v 1.8; P < .001). Conclusion Patients who are receiving active treatment for cancer, and even those who are willing to stop treatment, express a clear preference for alternative supportive care services over traditional hospice services. Supportive care programs for patients with advanced cancer should reconsider the services that they offer and might seek to include novel services in addition to, or perhaps instead of, traditional hospice services. C1 [Casarett, David] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Leonard Davis Inst Hlth Econ, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Casarett, D (reprint author), Univ Penn, Sch Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [R01CA109540] NR 50 TC 7 Z9 7 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2008 VL 26 IS 8 BP 1296 EP 1301 DI 10.1200/JCO.2007.12.8371 PG 6 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300019 PM 18323553 ER PT J AU Edwards, KE Neville, BA Cook, EF Aldridge, SH Dussel, V Wolfe, J AF Edwards, Kelly E. Neville, Bridget A. Cook, Earl F., Jr. Aldridge, Sarah H. Dussel, Veronica Wolfe, Joanne TI Understanding of prognosis and goals of care among couples whose child died of cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PALLIATIVE CARE; LIFE; PARENTS; SYMPTOMS; QUALITY; FATHERS; PERSPECTIVES; NATIONWIDE; IMPACT; END AB Purpose Little is known about how couples care for the terminally ill child with cancer. We assessed both parents' understanding of prognosis and treatment goals for children with cancer and explored whether sex mediates these views. We also investigated whether discordance within couples regarding treatment goals was related to parental perception of the child's end-of-life (EOL) experience. Methods We surveyed mothers and fathers of children who died of cancer and were cared for at Children's Hospital (Boston, MA) and the Dana-Farber Cancer Institute (Boston, MA) between 2000 and 2004. Our sample included 38 couples (response rate, 56%). Results Willingness to participate did not differ by sex. At diagnosis, fathers and mothers held a similar understanding of the child's prognosis, and 58% of couples agreed on the goal of cure. During the EOL period, a majority of fathers and mothers reported lessening suffering as the primary goal. However, within couples there was poor agreement about the primary goal of care (kappa = 0.07). When parents did not agree on the primary goal of lessening suffering, both parents were more likely to report that the child suffered significantly from cancer-directed treatment (P = .03). Conclusion Though parent goals are often concurrent at diagnosis, they frequently differ during the EOL period. Parent disagreement about the goal of lessening suffering at the EOL appears to impact how parents describe their child's experience of suffering. Creating opportunities for parents to work through their goals together may lead to improvements in the child's EOL experience. C1 [Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM Joanne_wolfe@dfci.harvard.edu FU NCI NIH HHS [K07 CA096746, 5 K07 CA096746]; PHS HHS [T32HP10018] NR 18 TC 30 Z9 30 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2008 VL 26 IS 8 BP 1310 EP 1315 DI 10.1200/JCO.2007.13.4056 PG 6 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300021 PM 18323555 ER PT J AU Kauff, ND Domchek, SM Friebel, TM Robson, ME Lee, J Garber, JE Isaacs, C Evans, DG Lynch, H Eeles, RA Neuhausen, SL Daly, MB Matloff, E Blum, JL Sabbatini, P Barakat, RR Hudis, C Norton, L Offit, K Rebbeck, TR AF Kauff, Noah D. Domchek, Susan M. Friebel, Tara M. Robson, Mark E. Lee, Johanna Garber, Judy E. Isaacs, Claudine Evans, D. Gareth Lynch, Henry Eeles, Rosalind A. Neuhausen, Susan L. Daly, Mary B. Matloff, Ellen Blum, Joanne L. Sabbatini, Paul Barakat, Richard R. Hudis, Clifford Norton, Larry Offit, Kenneth Rebbeck, Timothy R. TI Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: A multicenter, prospective study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID BRCA2 MUTATION CARRIERS; BILATERAL PROPHYLACTIC OOPHORECTOMY; ESTROGEN-RECEPTOR STATUS; OVARIAN-CANCER; INHERITED MUTATIONS; FOLLOW-UP; TAMOXIFEN; WOMEN; PENETRANCE; REDUCTION AB Purpose Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated. C1 [Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, Clin Genet & Gynecol Serv, New York, NY 10021 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Manchester Reg Genet Serv, Manchester, Lancs, England. Creighton Univ, Sch Med, Omaha, NE 68178 USA. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Univ Calif Irvine, Irvine, CA USA. Yale Univ, New Haven, CT USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. RP Kauff, ND (reprint author), Mem Sloan Kettering Canc Ctr, Clin Genet & Gynecol Serv, 1275 York Ave,Box 192, New York, NY 10021 USA. EM kauffn@mskcc.org OI Eeles, Rosalind/0000-0002-3698-6241; Norton, Larry/0000-0003-3701-9250; Kauff, Noah/0000-0001-7242-6156; Robson, Mark/0000-0002-3109-1692; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK [C5047/A3354]; NCI NIH HHS [R01 CA083855-04, R01 CA074415, R01 CA083855, R01 CA083855-01, R01 CA083855-02, R01 CA083855-03, R01 CA083855-05, R01 CA083855-06, R01 CA083855-07, R01 CA083855-08, R01 CA083855-09, R01 CA083855-10, R01 CA083855-11, R01 CA102776, R01 CA102776-01A1, R01 CA102776-02, R01 CA102776-03, R01 CA102776-04, R01 CA102776-05, R01-CA102776, R01-CA74415, R01-CA83855] NR 35 TC 234 Z9 239 U1 1 U2 16 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 MAR 10 PY 2008 VL 26 IS 8 BP 1331 EP 1337 DI 10.1200/JCO.2007.13.9626 PG 7 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300024 PM 18268356 ER PT J AU Liben, S Papadatou, D Wolfe, J AF Liben, Stephen Papadatou, Danai Wolfe, Joanne TI Paediatric palliative care: challenges and emerging ideas SO LANCET LA English DT Review ID OF-LIFE CARE; FACULTY-DEVELOPMENT PROGRAM; PHYSICIAN-ASSISTED SUICIDE; CHILDRENS HOSPICE PROGRAM; SIOP WORKING COMMITTEE; OREGON CANCER-PATIENTS; NATIONWIDE FOLLOW-UP; MEDICAL-EDUCATION; DYING CHILDREN; HEALTH-PROFESSIONALS AB Paediatric palliative care is an emerging subspecialty that focuses on achieving the best possible quality of life for children with life-threatening conditions and their families. To achieve this goal, the individuals working in this field need to: clearly define the population served; better understand the needs of children with fife-threatening conditions and their families; develop an approach that will be appropriate across different communities; provide care that responds adequately to suffering; advance strategies that support caregivers and health-care providers; and promote needed change by cultivating educational programmes. Despite these challenges, advances in paediatric palliative care have been achieved in a short period of time; we expect far greater progress as the field becomes more formalised and research networks are established. C1 [Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Populat Sci, Boston, MA 02115 USA. [Liben, Stephen] McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Montreal, PQ, Canada. [Papadatou, Danai] Univ Athens, Fac Nursing, GR-10679 Athens, Greece. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM joanne_wolfe@dfci.harvard.edu FU NCI NIH HHS [5 K07 CA 096746] NR 168 TC 85 Z9 86 U1 5 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 8 PY 2008 VL 371 IS 9615 BP 852 EP 864 DI 10.1016/S0140-6736(07)61203-3 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 272NQ UT WOS:000253866500032 PM 17707080 ER PT J AU Katavetin, P Inagi, R Miyata, T Tanaka, T Sassa, R Ingelfinger, JR Fujita, T Nangaku, M AF Katavetin, Pisut Inagi, Reiko Miyata, Toshio Tanaka, Tetsuhiro Sassa, Ryoji Ingelfinger, Julie R. Fujita, Toshiro Nangaku, Masaomi TI Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE VEGF; albumin; hypoxia; proximal tubule; HIF; proteinuria ID PROXIMAL TUBULAR CELLS; NF-KAPPA-B; RENAL-DISEASE; FACTOR GENE; AMINONUCLEOSIDE NEPHROSIS; TUBULOINTERSTITIAL INJURY; EPITHELIAL-CELLS; ANGIOTENSIN-II; HIF-ALPHA; PROTEINURIA AB Reduction of vascular endothelial growth factor (VEGF) expression plays a crucial role in chronic kidney disease (CKD). In order to clarify a cause of VEGF suppression in CKD, we examined an interaction between proteinuria and VEGF. Rat proximal tubular cells were subjected to hypoxia with or without albumin to mimic proteinuric conditions, and VEGF expression was assessed by real-time quantitative PCR and enzyme-linked immunosorbent assays. Albumin significantly reduced VEGF expression under hypoxia. Luciferase activity controlled by hypoxia-responsive element (HRE) was suppressed by albumin, demonstrating suppression of the hypoxia-inducible factor (HIF)/HRE pathway. Studies utilizing a proteasome inhibitor and a prolyl hydroxylase inhibitor showed that mechanisms of HIF/HRE pathway suppression by albumin load did not involve degradation of HIT protein levels. Further, albumin did not change HIF mRNA levels. Our data, for the first time, suggest a clear 'link' between proteinuria and hypoxia, the two principal pathogenic factors for CKD progression. (c) 2007 Elsevier Inc. All rights reserved. C1 [Katavetin, Pisut; Inagi, Reiko; Tanaka, Tetsuhiro; Fujita, Toshiro; Nangaku, Masaomi] Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 113, Japan. [Katavetin, Pisut] Chulalongkorn Univ, Dept Med, Div Nephrol, Bangkok, Thailand. [Miyata, Toshio] Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591100, Japan. [Miyata, Toshio] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Sassa, Ryoji] Okazaki Kita Clin, Aichi, Japan. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 113, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 NR 38 TC 13 Z9 16 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 7 PY 2008 VL 367 IS 2 BP 305 EP 310 DI 10.1016/j.bbrc.2007.12.086 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 257YE UT WOS:000252834700011 PM 18155159 ER PT J AU Koralov, SB Muljo, SA Galler, GR Krek, A Chakraborty, T Kanellopoulou, C Jensen, K Cobb, BS Merkenschlager, M Rajewsky, N Rajewsky, K AF Koralov, Sergei B. Muljo, Stefan A. Galler, Gunther R. Krek, Azra Chakraborty, Tirtha Kanellopoulou, Chryssa Jensen, Kari Cobb, Bradley S. Merkenschlager, Matthias Rajewsky, Nikolaus Rajewsky, Klaus TI Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage SO CELL LA English DT Article ID TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; HEAVY-CHAIN; TRANSGENIC MICE; MESSENGER-RNAS; ENZYME DICER; MICRORNA; BIM; DIFFERENTIATION; TRANSCRIPTION; EXPRESSION AB To explore the role of Dicer-dependent control mechanisms in B lymphocyte development, we ablated this enzyme in early B cell progenitors. This resulted in a developmental block at the pro- to pre-B cell transition. Gene-expression profiling revealed a miR-17 similar to 92 signature in the 3'UTRs of genes upregulated in Dicer-deficient pro-B cells; a top miR-17 similar to 92 target, the proapoptotic molecule Bim, was highly upregulated. Accordingly, B cell development could be partially rescued by ablation of Bim or transgenic expression of the prosurvival protein Bcl-2. This allowed us to assess the impact of Dicer deficiency on the V(D)J recombination program in developing B cells. We found intact Ig gene rearrangements in immunoglobulin heavy (IgH) and kappa chain loci, but increased sterile transcription and usage of D-H elements of the DSP family in IgH, and increased N sequence addition in Ig kappa due to deregulated transcription of the terminal deoxynucleotidyl transferase gene. C1 [Koralov, Sergei B.; Muljo, Stefan A.; Galler, Gunther R.; Chakraborty, Tirtha; Jensen, Kari; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Koralov, Sergei B.; Muljo, Stefan A.; Galler, Gunther R.; Chakraborty, Tirtha; Jensen, Kari; Rajewsky, Klaus] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Krek, Azra; Rajewsky, Nikolaus] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. [Krek, Azra] NYU, Dept Phys, New York, NY 10003 USA. [Kanellopoulou, Chryssa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Cobb, Bradley S.; Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, Lymphocyte Dev Grp, MRC, Ctr Clin Sci, London W12 0NN, England. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu RI Muljo, Stefan/F-5671-2015; OI Muljo, Stefan/0000-0003-1013-446X; Merkenschlager, Matthias/0000-0003-2889-3288 FU Medical Research Council [MC_U120027516]; NIAID NIH HHS [AI-060302] NR 53 TC 349 Z9 370 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 7 PY 2008 VL 132 IS 5 BP 860 EP 874 DI 10.1016/j.cell.2008.02.020 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VY UT WOS:000253818000022 PM 18329371 ER PT J AU Ventura, A Young, AG Winslow, MM Lintault, L Meissner, A Erkeland, SJ Newman, J Bronson, RT Crowley, D Stone, JR Jaenisch, R Sharp, PA Jacks, T AF Ventura, Andrea Young, Amanda G. Winslow, Monte M. Lintault, Laura Meissner, Alex Erkeland, Stefan J. Newman, Jamie Bronson, Roderick T. Crowley, Denise Stone, James R. Jaenisch, Rudolf Sharp, Phillip A. Jacks, Tyler TI Targeted deletion reveals essential and overlapping functions of the miR-17 similar to 92 family of miRNA clusters SO CELL LA English DT Article ID MAMMALIAN MICRORNA TARGETS; MESSENGER-RNA; CELL-PROLIFERATION; MIR-17-92 CLUSTER; LUNG CANCERS; MICE LACKING; BCL-2 FAMILY; NORMAL MOUSE; EXPRESSION; LET-7 AB miR-17 similar to 92, miR-106b similar to 25, and miR-106a similar to 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17 similar to 92 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR17 similar to 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 similar to 92 cluster is also essential for B cell development. Absence of miR-17 similar to 92 leads to increased levels of the proapoptotic protein Bim and inhibits B cell development at the pro-Bto pre-B transition. Furthermore, while ablation of miR-106b similar to 25 or miR-106a similar to 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b similar to 25 and miR-17 similar to 92 die at midgestation. These results provide key insights into the physiologic functions of this family of microRNAs and suggest a link between the oncogenic properties of miR-17 similar to 92 and its functions during B lymphopoiesis and lung development. C1 [Ventura, Andrea; Young, Amanda G.; Winslow, Monte M.; Lintault, Laura; Newman, Jamie; Crowley, Denise; Sharp, Phillip A.; Jacks, Tyler] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Meissner, Alex; Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. [Erkeland, Stefan J.] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands. [Bronson, Roderick T.] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA USA. [Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Ventura, Andrea/F-1789-2011; OI Ventura, Andrea/0000-0003-4320-9907 FU Howard Hughes Medical Institute; NCI NIH HHS [2-PO1-CA42063-21, P01 CA042063, P01 CA042063-21A10012, P01 CA042063-220012, P30 CA014051, P30 CA014051-34, P30 CA014051-35, P30 CA014051-36, P30-CA14051]; NIAID NIH HHS [U19 AI056900]; NIGMS NIH HHS [R01 GM034277, R01-GM34277] NR 52 TC 858 Z9 916 U1 9 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 7 PY 2008 VL 132 IS 5 BP 875 EP 886 DI 10.1016/j.cell.2008.02.019 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VY UT WOS:000253818000023 PM 18329372 ER PT J AU Hoe, HS Minami, SS Makarova, A Lee, J Hyman, BT Matsuoka, Y Rebeck, GW AF Hoe, Hyang-Sook Minami, S. Sakura Makarova, Alexandra Lee, Jiyeon Hyman, Bradley T. Matsuoka, Yasuji Rebeck, G. William TI Fyn modulation of dab1 effects on amyloid precursor protein and ApoE receptor 2 processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN-E RECEPTORS; ALZHEIMERS-DISEASE; TYROSINE KINASE; BRAIN-DEVELOPMENT; BINDING DOMAIN; LIGAND-BINDING; DISABLED 1; PHOSPHORYLATION; DEGRADATION; ADAPTER AB Dab1 is an intracellular adaptor protein that interacts with amyloid precursor protein (APP) and apoE receptor 2 (apoEr2), increases their levels on the cell surface, and increases their cleavage by alpha-secretases. To investigate the mechanism underlying these alterations in processing and trafficking of APP and apoEr2, we examined the effect of Fyn, an Src family-tyrosine kinase known to interact with and phosphorylate Dab1. Co-immunoprecipitation, co-immunostaining, and fluorescence lifetime imaging demonstrated an association between Fyn and APP. Fyn induced phosphorylation of APP at Tyr-757 of the (757)YENPTY(762) motif and increased cell surface expression of APP. Overexpression of Fyn alone did not alter levels of sAPP alpha or cytoplasmic C-terminal fragments, although it significantly decreased production of A beta. However, in the presence of Dab1, Fyn significantly increased sAPP alpha and C-terminal fragments. Fyn-induced APP phosphorylation and cell surface levels of APP were potentiated in the presence of Dab1. Fyn also induced phosphorylation of apoEr2 and increased its cell surface levels and, in the presence of Dab1, affected processing of its C-terminal fragment. In vivo studies showed that sAPP alpha was decreased in the Fyn knock-out, supporting a role for Fyn in APP processing. These data demonstrate that Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2. C1 [Hoe, Hyang-Sook; Minami, S. Sakura; Rebeck, G. William] Georgetown Univ, Ctr Med, Dept Neurosci, Washington, DC 20057 USA. [Minami, S. Sakura; Matsuoka, Yasuji] Georgetown Univ, Ctr Med, Dept Neurol, Washington, DC 20057 USA. [Makarova, Alexandra; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Disorders, Dept Neurol, Charlestown, MA 02129 USA. [Lee, Jiyeon] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Lee, Jiyeon] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Rebeck, GW (reprint author), Georgetown Univ, Ctr Med, Dept Neurosci, 3970 Reservoir Rd NW, Washington, DC 20057 USA. EM gwr2@georgetown.edu FU NIA NIH HHS [AG 022455, AG 14473, P01 AG030128] NR 36 TC 29 Z9 30 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 MAR 7 PY 2008 VL 283 IS 10 BP 6288 EP 6299 DI 10.1074/jbc.M704140200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 271HM UT WOS:000253779500036 PM 18089558 ER PT J AU Dietz, H Rief, M AF Dietz, Hendrik Rief, Matthias TI Elastic bond network model for protein unfolding mechanics SO PHYSICAL REVIEW LETTERS LA English DT Article ID MOLECULE FORCE SPECTROSCOPY; SINGLE PROTEIN; SIMULATIONS; STABILITY; PATHWAYS; TOPOLOGY; TENASCIN; ADHESION; REPEATS; MODULES AB Recent advances in single molecule mechanics have made it possible to investigate the mechanical anisotropy of protein stability in great detail. A quantitative prediction of protein unfolding forces at experimental time scales has so far been difficult. Here, we present an elastically bonded network model to describe the mechanical unfolding forces of green fluorescent protein in eight different pulling directions. The combination of an elastic network and irreversible bond fracture kinetics offers a new concept to understand the determinants of mechanical protein stability. C1 [Dietz, Hendrik] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dietz, Hendrik] Harvard Univ, Sch Med, BCMP, Boston, MA 02115 USA. [Rief, Matthias] Tech Univ Munich, Dept Phys, D-85748 Garching, Germany. RP Dietz, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM dietz@ph.tum.de; mrief@ph.tum.de RI Dietz, Hendrik/A-6622-2008 NR 36 TC 55 Z9 56 U1 2 U2 14 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 EI 1079-7114 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAR 7 PY 2008 VL 100 IS 9 AR 098101 DI 10.1103/PhysRevLett.100.098101 PG 4 WC Physics, Multidisciplinary SC Physics GA 271BS UT WOS:000253764500073 PM 18352751 ER PT J AU Lu, HM AF Lu, Hsiao-Ming TI A potential method for in vivo range verification in proton therapy treatment SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CURRENT MODULATION; RADIOTHERAPY; SYSTEM; PATIENT; MOTION AB Proton therapy potentially offers excellent dose conformality and reduction in integral dose. The superior dose distribution is, however, much more sensitive to the radiological depth along the beam path than for photon fields. Variations in this depth due to inaccurate planning calculation, setup uncertainty, respiration-induced organ motion, etc, could result in either an 'undershooting', missing the distal portion of the target volume entirely, or an 'overshooting', delivering the full prescription dose to the normal tissue beyond the target volume. In vivo dose verification plays an important role in the quality assurance of the treatments. The point dose measurements widely used for photon treatments are, however, insufficient for protons due to the particular characteristics of the proton depth-dose distribution. In this work, we explore a method for in vivo range verifications in proton treatments using range-modulated passive scattering fields. The method utilizes the time dependence of the dose distribution delivered by these fields. By measuring the time dependence of the dose rate at any point in the target volume, the residual range of the beam at this point can be obtained with millimeter accuracy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Francis H Burr Proton Therapy C, Boston, MA 02114 USA. RP Lu, HM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Francis H Burr Proton Therapy C, Boston, MA 02114 USA. EM hmlu@partners.org FU NCI NIH HHS [5 P01 CA21239-24] NR 16 TC 36 Z9 36 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2008 VL 53 IS 5 BP 1413 EP 1424 DI 10.1088/0031-9155/53/5/016 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 276WY UT WOS:000254175600017 PM 18296770 ER PT J AU Dash, PK Siddappa, NB Mangaiarkarasi, A Mahendarkar, AV Roshan, P Anand, KK Mahadevan, A Satishchandra, P Shankar, SK Prasad, VR Ranga, U AF Dash, Prasanta K. Siddappa, Nagadenahalli B. Mangaiarkarasi, Asokan Mahendarkar, Aruna V. Roshan, Padmanabhan Anand, Krishnamurthy Kumar Mahadevan, Anita Satishchandra, Parthasarathy Shankar, Susarla K. Prasad, Vinayaka R. Ranga, Udaykumar TI Exceptional molecular and coreceptor-requirement properties of molecular clones isolated from an Human Immunodeficiency Virus Type-I subtype C infection SO RETROVIROLOGY LA English DT Article ID N-LINKED GLYCOSYLATION; LONG TERMINAL REPEAT; HUMAN LYMPHOID-TISSUE; HIV TYPE-1; DISEASE PROGRESSION; GENETIC SUBTYPES; V3 LOOP; ENVELOPE GLYCOPROTEIN; SEQUENCE ALIGNMENT; CXCR4 CORECEPTORS AB Background: The pathogenic significance of coreceptor switch in the viral infection of HIV-1 is not completely understood. This situation is more complex in subtype C infection where coreceptor switch is either absent or extremely rare. To gain insights into the mechanisms that underlie coreceptor requirement of subtype C, we screened several primary viral isolates and identified a clinical sample that demonstrated a potential to grow on standard T-cell lines with no detectable CCR5 expression. The subject was diagnosed with HIV-1 associated dementia in the absence of opportunistic infections of the brain. To isolate molecular clones from this virus, we devised a novel strategy based on anchor primers that target a sequence in the reverse transcriptase, highly conserved among diverse subtypes of HIV-1. Results: Using this strategy, we isolated 8 full-length molecular clones from the donor. Two of the eight molecular clones, 03In94_D17 and 03In94_D24, (D17 and D24) generated replication-competent viruses. Phylogenetic analysis of the full-length viral sequences revealed that both clones were non-recombinant subtype C viruses. They contain intact open reading frames in all the viral proteins. Both the viral clones are endowed with several unique molecular and biological properties. The viral promoter of the clones is characterized by the presence of four NF-kB binding elements, a feature rarely seen in the subtype C HIV-1 LTR. Interestingly, we identified the coexistence of two different forms of Rev, a truncated form common to subtype C and a full-length form less common for this subtype, in both proviral and plasma virus compartments. An exceptional property of the viruses, atypical of subtype C, is their ability to use a wide range of coreceptors including CCR5, CXCR4, and several others tested. Sequence analysis of Env of D17 and D24 clones identified differences within the variable loops providing important clues for the expanded coreceptor use. The V1, V2 and V4 loops in both of the molecular clones are longer due to the insertion of several amino acid residues that generated potential N-linked glycosylation sites. Conclusion: The exceptional biological and molecular properties of these clones make them invaluable tools to understand the unique pathogenic characteristics of subtype C. C1 [Dash, Prasanta K.; Siddappa, Nagadenahalli B.; Mangaiarkarasi, Asokan; Mahendarkar, Aruna V.; Roshan, Padmanabhan; Anand, Krishnamurthy Kumar; Ranga, Udaykumar] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Mol Virol Lab, Bangalore 560012, Karnataka, India. [Mahadevan, Anita; Shankar, Susarla K.] Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India. [Prasad, Vinayaka R.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Siddappa, Nagadenahalli B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ranga, U (reprint author), Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Mol Virol Lab, Bangalore 560012, Karnataka, India. EM pkdash@jncasr.ac.in; Nb_Siddappa@DFCI.HARVARD.EDU; mangai@jncasr.ac.in; aruna@jncasr.ac.in; rosaak@gmail.com; anandk@jncasr.ac.in; anita_mahadevan@yahoo.com; psatish@nimhans.kar.nic.in; shankar@nimhans.kar.nic.in; prasad@aecom.yu.edu; udaykumar@jncasr.ac.in FU FIC NIH HHS [D43-TW01403, D43 TW001403]; NIMH NIH HHS [R01 MH083579] NR 96 TC 20 Z9 23 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAR 7 PY 2008 VL 5 AR 25 DI 10.1186/1742-4690-5-25 PG 22 WC Virology SC Virology GA 295MD UT WOS:000255477700001 PM 18328091 ER PT J AU Silverman, JM Schriaider-Beeri, M Grossman, HT Schmeidler, J Wang, JY Lally, RC AF Silverman, Jeremy M. Schriaider-Beeri, Michal Grossman, Hillel T. Schmeidler, James Wang, Joy Y. Lally, Rachel C. TI A phenotype for genetic studies of successful cognitive aging SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dementia; genetic epidemiology; family history; successful aging ID ONSET ALZHEIMERS-DISEASE; FAMILY HISTORY METHOD; APOLIPOPROTEIN-E; DEMENTIA QUESTIONNAIRE; MEMORY PERFORMANCE; PROTECTIVE FACTOR; SWEDISH TWINS; OLDEST-OLD; RISK; ALLELE AB Survival from Alzheimer's disease (AD) and other dementias into late old age may be a useful phenotype for genetic studies of successful cognitive aging. To support molecular genetics studies for successful cognitive aging, we conducted a two-stage study to determine an optimal age phenotype for successful cognitive aging. First, risk of AD was evaluated, through informant interviews, in 4,794 parents and siblings of 976 elderly nondemented probands who were divided into three different proband age groups: those aged 60-74, 75-89, and 90+. Relatives of probands aged 90+ had a significantly lower risk than the relatives of the other two proband groups. Second, this sample was combined with an earlier sample (combined nondemented elderly probands: n = 2,025; relatives: n = 10,506), and a series of proband age groups (i.e., 75-79, 80-84, 85-89, 90+) were used to determine which optimally identifies a group of relatives with low AD risk. Using the relatives of the nondemented proband aged 60-74 as the reference group, there were reductions in cumulative risk among relatives of probands aged 85-89 and 90+, but only the latter group also showed significant reductions to the relatives of probands aged 75-79, 80-84, and 85-89. This pattern of results varied little by sex. Finally, cumulative AD risk curves were similar between relatives of probands aged 90-94 and 95+. These results suggest that age 90 is an optima age threshold to use for both men and women in genetic studies seeking to identify genes associated with successful cognitive aging. (c) 2007 Wiley-Liss, Inc. C1 [Silverman, Jeremy M.; Schriaider-Beeri, Michal; Grossman, Hillel T.; Schmeidler, James; Wang, Joy Y.; Lally, Rachel C.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Silverman, Jeremy M.; Grossman, Hillel T.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Silverman, JM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230 1 Guestave L Levy Pl,, New York, NY 10029 USA. EM jeremy.silverman@mssm.edu FU NIA NIH HHS [K01-AG023515, P01-AG05138, R03-AG24601, P01-AG02219] NR 45 TC 8 Z9 8 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR 5 PY 2008 VL 147B IS 2 BP 167 EP 173 DI 10.1002/ajmg.b.30483 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 271OS UT WOS:000253798700003 PM 18023042 ER PT J AU Parchman, ML Pugh, JA Culler, SD Noel, PH Arar, NH Romero, RL Palmer, RF AF Parchman, Michael L. Pugh, Jacqueline A. Culler, Steven D. Noel, Polly H. Arar, Nedal H. Romero, Raquel L. Palmer, Raymond F. TI A group randomized trial of a complexity-based organizational intervention to improve risk factors for diabetes complications in primary care settings: study protocol SO IMPLEMENTATION SCIENCE LA English DT Article ID GENERAL-PRACTICE; CHRONIC ILLNESS; GLUCOSE CONTROL; MANAGED CARE; QUALITY; COMMUNICATION; CLINICS; SYSTEM AB Background: Most patients with type 2 diabetes have suboptimal control of their glucose, blood pressure (BP), and lipids-three risk factors for diabetes complications. Although the chronic care model (CCM) provides a roadmap for improving these outcomes, developing theoretically sound implementation strategies that will work across diverse primary care settings has been challenging. One explanation for this difficulty may be that most strategies do not account for the complex adaptive system (CAS) characteristics of the primary care setting. A CAS is comprised of individuals who can learn, interconnect, self-organize, and interact with their environment in a way that demonstrates non-linear dynamic behavior. One implementation strategy that may be used to leverage these properties is practice facilitation (PF). PF creates time for learning and reflection by members of the team in each clinic, improves their communication, and promotes an individualized approach to implement a strategy to improve patient outcomes. Specific objectives: The specific objectives of this protocol are to: evaluate the effectiveness and sustainability of PF to improve risk factor control in patients with type 2 diabetes across a variety of primary care settings; assess the implementation of the CCM in response to the intervention; examine the relationship between communication within the practice team and the implementation of the CCM; and determine the cost of the intervention both from the perspective of the organization conducting the PF intervention and from the perspective of the primary care practice. Intervention: The study will be a group randomized trial conducted in 40 primary care clinics. Data will be collected on all clinics, with 60 patients in each clinic, using a multi-method assessment process at baseline, 12, and 24 months. The intervention, PF, will consist of a series of practice improvement team meetings led by trained facilitators over 12 months. Primary hypotheses will be tested with 12-month outcome data. Sustainability of the intervention will be tested using 24 month data. Insights gained will be included in a delayed intervention conducted in control practices and evaluated in a pre-post design. Primary and secondary outcomes: To test hypotheses, the unit of randomization will be the clinic. The unit of analysis will be the repeated measure of each risk factor for each patient, nested within the clinic. The repeated measure of glycosylated hemoglobin AIc will be the primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as secondary outcomes. To study change in risk factor level, a hierarchical or random effect model will be used to account for the nesting of repeated measurement of risk factor within patients and patients within clinics. This protocol follows the CONSORT guidelines and is registered per ICMJE guidelines: Clinical Trial Registration Number: NCT00482768 C1 [Parchman, Michael L.; Pugh, Jacqueline A.; Noel, Polly H.; Arar, Nedal H.; Romero, Raquel L.; Palmer, Raymond F.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, San Antonio, TX USA. [Parchman, Michael L.; Romero, Raquel L.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Pugh, Jacqueline A.; Noel, Polly H.; Arar, Nedal H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Culler, Steven D.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, San Antonio, TX USA. EM parchman@uthscsa.edu; pugh@uthscsa.edu; sculler@sph.emory.edu; noelp@uthscsa.edu; ararn@uthscsa.edu; romeror0@uthscsa.edu; palmerr@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU National Institute of Diabetes, Digestive and Kidney Disorders [R18 DK 075692] FX This study, is funded by a grant from the National Institute of Diabetes, Digestive and Kidney Disorders. (R18 DK 075692), follows the CONSORT guidelines, and is registered per ICMJE guidelines: Clinical Trial Registration Number: NCT00482768. NR 49 TC 15 Z9 15 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAR 5 PY 2008 VL 3 AR 15 DI 10.1186/1748-5908-3-15 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QS UT WOS:000265149800001 PM 18321386 ER PT J AU Willins, J Kachnic, L AF Willins, John Kachnic, Lisa TI Clinically relevant standards for intensity-modulated radiation therapy dose prescription SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TARGET VOLUMES C1 [Willins, John; Kachnic, Lisa] Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Willins, John; Kachnic, Lisa] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willins, J (reprint author), Boston Med Ctr, Dept Radiat Oncol, Moakley Bldg,Ste LL100,830 Harriston Ave, Boston, MA 02118 USA. EM john.willins@bmc.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 5 PY 2008 VL 100 IS 5 BP 288 EP U4 DI 10.1093/jnci/djn039 PG 3 WC Oncology SC Oncology GA 271OD UT WOS:000253796800001 PM 18314470 ER PT J AU Badgaiyan, RD Fischman, AJ Alpert, NM AF Badgaiyan, Rajendra D. Fischman, Alan J. Alpert, Nathaniel M. TI Explicit motor memory activates the striatal dopamine system SO NEUROREPORT LA English DT Article DE dopamine; explicit memory; molecular imaging; motor memory; raclopride; serial reaction time task ID PROCESS DISSOCIATION PROCEDURE; REACTION-TIME-TASK; PARKINSONS-DISEASE; IMPLICIT; CORTEX; PET; ORGANIZATION; RELEASE AB We studied the pattern of striatal dopamine release during performance of an explicit motor memory task in healthy volunteers. The release was estimated by dynamically measuring concentration of a dopamine ligand using a positron emission tomography camera. An increased release of endogenous dopamine in the dorsomedial aspect of posterior putamen and in the anterior part of the caudate bilaterally was observed, during task performance. As we have earlier observed dopamine release in all of these areas, except the right putamen, in an implicit motor memory task, it seems that the striatal dopaminergic network for implicit and explicit motor memories are essentially similar. C1 [Badgaiyan, Rajendra D.; Fischman, Alan J.; Alpert, Nathaniel M.] Massachusetts Gen Hosp, Div Nucl Med White 427, Boston, MA 02114 USA. [Badgaiyan, Rajendra D.; Fischman, Alan J.; Alpert, Nathaniel M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Badgaiyan, Rajendra D.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. RP Badgaiyan, RD (reprint author), Massachusetts Gen Hosp, Div Nucl Med White 427, 55 Fruit St, Boston, MA 02114 USA. EM rajendra@wjh.harvard.edu FU NIMH NIH HHS [1 R21 MH 073624] NR 25 TC 25 Z9 25 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 5 PY 2008 VL 19 IS 4 BP 409 EP 412 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 272UF UT WOS:000253884900004 PM 18287937 ER PT J AU Paruchuri, V Prasad, A McHugh, K Bhat, HK Polyak, K Ganju, RK AF Paruchuri, Vikram Prasad, Anil McHugh, Kevin Bhat, Hari K. Polyak, Kornelia Ganju, Ramesh K. TI S100A7-Downregulation Inhibits Epidermal Growth Factor-Induced Signaling in Breast Cancer Cells and Blocks Osteoclast Formation SO PLOS ONE LA English DT Article AB S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF) induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation. C1 [Paruchuri, Vikram; Prasad, Anil; Ganju, Ramesh K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Expt Med, Boston, MA 02215 USA. [McHugh, Kevin] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Div Rheumatol, Boston, MA USA. [Bhat, Hari K.] Columbia Univ, Mailman Sch Public Hlth, Dept Environmental Hlth Sci, New York, NY USA. [Polyak, Kornelia] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. RP Ganju, RK (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Expt Med, Boston, MA 02215 USA. EM ramesh.ganju@osumc.edu FU National Institutes of Health [CA109527]; Susan G. Komen Breast Cancer Foundation; Department of Defense Award [W81XWH-05-1-0465] FX The research is supported in part by a grant from the National Institutes of Health CA109527, Susan G. Komen Breast Cancer Foundation, and the Department of Defense Award # W81XWH-05-1-0465 to RKG. NR 47 TC 24 Z9 29 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 5 PY 2008 VL 3 IS 3 AR e1741 DI 10.1371/journal.pone.0001741 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367XT UT WOS:000260586600036 PM 18320059 ER PT J AU Qaseem, A Snow, V Cross, JT Forciea, MA Hopkins, R Shekelle, P Adelman, A Mehr, D Schellhase, K Campos-Outcalt, D Santaguida, P Owens, DK AF Qaseem, Amir Snow, Vincenza Cross, J. Thomas, Jr. Forciea, Mary Ann Hopkins, Robert, Jr. Shekelle, Paul Adelman, Alan Mehr, David Schellhase, Kenneth Campos-Outcalt, Doug Santaguida, Pasqualina Owens, Douglas K. CA Joint Amer Coll Phys Amer Acad Fam TI Current Pharmacologic treatment of dementia: A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MODERATE ALZHEIMERS-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PROBABLE VASCULAR DEMENTIA; MILD COGNITIVE IMPAIRMENT; DOUBLE-BLIND TRIAL; CEREBROVASCULAR-DISEASE; DONEPEZIL TREATMENT; MEMANTINE TREATMENT; PARKINSONS-DISEASE AB Description: The American College of Physicians and American Academy of Family Physicians developed this guideline to present the available evidence on current pharmacologic treatment of dementia. Methods: The targeted literature search included evidence related to the effectiveness of 5 U. S. Food and Drug Administration approved pharmacologic therapies for dementia for outcomes in the domains of cognition, global function, behavior/ mood, and quality of life/ activities of daily living. Recommendation 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. ( Grade: weak recommendation, moderate-quality evidence.) Recommendation 2: Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia. ( Grade: weak recommendation, low-quality evidence.) Recommendation 3: There is an urgent need for further research on the clinical effectiveness of pharmacologic management of dementia. C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ Penn, Philadelphia, PA 19104 USA. Medstudy, Colorado Springs, CO USA. Univ Arkansas, Little Rock, AR 72204 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. RAND Corp, Santa Monica, CA USA. Penn State Univ, Hershey, PA USA. Univ Missouri, Sch Med, Columbia, MO USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Amer Acad Family Phys, Leawood, KS USA. McMaster Univ, Hamilton, ON, Canada. Univ Minnesota, Minneapolis, MN USA. Stanford Univ, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org OI Peterson, Kevin/0000-0002-6914-8586 NR 62 TC 147 Z9 160 U1 1 U2 9 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 MAR 4 PY 2008 VL 148 IS 5 BP 370 EP W82 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 268SX UT WOS:000253600800006 PM 18316755 ER PT J AU Lao, LJ Song, BB Chen, WL Marvizon, JCG AF Lao, Lijun Song, Bingbing Chen, Wenling Marvizon, Juan Carlos G. TI Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce mu-opioid receptor internalization in the presence of peptidase inhibitors SO BRAIN RESEARCH LA English DT Article DE dorsal horn; enkephalin; internalization; mu-opioid receptor; neurokinin 1 receptor; peptidase ID RAT SPINAL-CORD; ENKEPHALIN-LIKE MATERIAL; DORSAL-HORN NEURONS; SUBSTANCE-P RELEASE; MEDIAL PREOPTIC NUCLEUS; D-ASPARTATE RECEPTORS; NEUROKININ-1 RECEPTOR; DEGRADING ENZYMES; THERMAL STIMULI; CHRONIC CATHETERIZATION AB The internalization of p-opioid receptors (MORs) provides an ideal way to locate areas of opioid peptide release. We used this method to study opioid release in the spinal cord evoked by noxious stimuli in anesthetized rats. Previous studies have shown that opioids released in the spinal cord produce MOR internalization only when they are protected from peptidase degradation. Accordingly, rats were implanted with chronic intrathecal catheters that were used to inject a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) onto the lumbar spinal cord. Five minutes later, a noxious stimulus was delivered to the paw. Lumbar spinal segments were double-stained with antibodies against MORs and neurokinin 1 receptors (NK1Rs) using immuno fluorescence. Mechanical stimulation of the hindpaw consisted of repeated 10 s clamps with a hemostat for 10 min. in the ipsilateral dorsal horn, the stimulus produced abundant NK1R internalization in segments L3-L6, and a more modest but significant MOR internalization in segments L5 and L6. In the contralateral dorsal horn, NK1R was substantially lower and MOR internalization was negligible. The same mechanical stimulus applied to a forepaw did not produce NK1R or MOR internalization in the lumbar spinal cord. Thermal stimulation consisted of immersing a hindpaw in water at 52 degrees C for 2 min. It produced substantial NK1R internalization ipsilaterally in segment L6, but no MOR internalization. These results show that mechanical stimulation induces segmental opioid release, i.e., in the dorsal horn receiving the noxious signals and not in other spinal segments. (C) 2007 Elsevier B.V. All rights reserved. C1 [Marvizon, Juan Carlos G.] VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress & CURE,Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), VA Greater Los Angeles Hlthcare Syst, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu RI Chen, Wenling/A-4490-2012 FU NIDA NIH HHS [R01 DA012609, 2 R01-DA012609, R01 DA012609-07, R01 DA012609-08] NR 52 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 4 PY 2008 VL 1197 BP 85 EP 93 DI 10.1016/j.brainres.2007.12.040 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 275KS UT WOS:000254070900009 PM 18207137 ER PT J AU Nahrendorf, M Sosnovik, D Chen, JW Panizzi, P Figueiredo, JL Aikawa, E Libby, P Swirski, FK Weissleder, R AF Nahrendorf, Matthias Sosnovik, David Chen, John W. Panizzi, Peter Figueiredo, Jose-Luiz Aikawa, Elena Libby, Peter Swirski, Filip K. Weissleder, Ralph TI Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury SO CIRCULATION LA English DT Article DE inflammation; magnetic resonance imaging; myocardial infarction; myeloperoxidase; reperfusion ID ACUTE MYOCARDIAL-INFARCTION; STATINS; INFLAMMATION; SIZE; ATHEROSCLEROSIS; NEUTROPHILIA; PRETREATMENT; DYSFUNCTION; MECHANISMS; OUTCOMES AB Background-Ischemic injury of the myocardium causes timed recruitment of neutrophils and monocytes/macrophages, which produce substantial amounts of local myeloperoxidase (MPO). MPO forms reactive chlorinating species capable of inflicting oxidative stress and altering protein function by covalent modification. We have used a small-molecule, gadolinium-based activatable sensor for magnetic resonance imaging of MPO activity (MPO-Gd). MPO-Gd is first radicalized by MPO and then either spontaneously oligomerizes or binds to matrix proteins, all leading to enhanced spin-lattice relaxivity and delayed washout kinetics. We hypothesized that MPO imaging could be used to measure inflammatory responses after myocardial ischemia locally and noninvasively in a murine model. Methods and Results-We injected 0.3 mmol/kg MPO-Gd (or Gd-DTPA as control) and performed magnetic resonance imaging up to 120 minutes later in mice 2 days after myocardial infarction. The contrast-to-noise ratio (infarct versus septum) after Gd-DTPA injection peaked at 10 minutes and returned to preinjection values at 60 minutes. After injection of MPO-Gd, the contrast-to-noise ratio peaked later and was higher than Gd-DTPA (40.8 +/- 10.4 versus 10.5 +/- 0.2; P < 0.05). MPO imaging was validated by magnetic resonance imaging of MPO-/- mice and correlated well with immunoreactive staining (r(2) = 0.92, P = 0.05), tissue activity by guaiacol assay (r(2)=0.65, P<0.001), and immunoblotting. In time course imaging, activity peaked 2 days after coronary ligation. Flow cytometry of digested infarcts detected MPO in neutrophils and monocytes/macrophages. Furthermore, serial MPO imaging accurately tracked the antiinflammatory effects of atorvastatin therapy after ischemia-reperfusion injury. Conclusions-MPO-Gd enables in vivo assessment of MPO activity in injured myocardium. This approach allows noninvasive evaluation of the inflammatory response to ischemia and has the potential to guide the development of novel cardioprotective therapies. C1 [Nahrendorf, Matthias; Chen, John W.; Figueiredo, Jose-Luiz; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA USA. [Nahrendorf, Matthias; Sosnovik, David; Chen, John W.; Panizzi, Peter; Figueiredo, Jose-Luiz; Aikawa, Elena; Swirski, Filip K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Nahrendorf, Matthias; Sosnovik, David; Chen, John W.; Panizzi, Peter; Figueiredo, Jose-Luiz; Aikawa, Elena; Swirski, Filip K.; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Nahrendorf, Matthias; Aikawa, Elena; Libby, Peter; Weissleder, Ralph] Donald W Reynolds Cardiovasc Clin Res Ctr Arthero, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Sosnovik, David] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), 185 Cambridge St, Boston, MA 02114 USA. EM MNahrendorf@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU NCI NIH HHS [R24 CA092782-05, R24 CA092782, R24-CA92782]; NHLBI NIH HHS [5K08HL081170, R00 HL094533, R01 HL078641, R01 HL078641-03, R01-HL078641, U01 HL080731, U01 HL080731-03, U01-HL080731] NR 36 TC 98 Z9 100 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 4 PY 2008 VL 117 IS 9 BP 1153 EP 1160 DI 10.1161/CIRCULATIONAHA.107.756510 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271GA UT WOS:000253775700006 PM 18268141 ER PT J AU Norden, AD Young, GS Setayesh, K Muzikansky, A Klufas, R Ross, GL Ciampa, AS Ebbeling, LG Levy, B Drappatz, J Kesari, S Wen, PY AF Norden, A. D. Young, G. S. Setayesh, K. Muzikansky, A. Klufas, R. Ross, G. L. Ciampa, A. S. Ebbeling, L. G. Levy, B. Drappatz, J. Kesari, S. Wen, P. Y. TI Bevacizumab for recurrent malignant gliomas - Efficacy, toxicity, and patterns of recurrence SO NEUROLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II; PROGNOSTIC-FACTORS; TUMOR GRADE; IN-VIVO; GLIOBLASTOMA; ANGIOGENESIS; RADIOTHERAPY; THERAPY; CANCER AB Background: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor. Methods: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone. Results: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders. Conclusions: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth. C1 [Norden, A. D.; Ciampa, A. S.; Ebbeling, L. G.; Levy, B.; Drappatz, J.; Kesari, S.; Wen, P. Y.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Norden, A. D.; Ciampa, A. S.; Ebbeling, L. G.; Levy, B.; Drappatz, J.; Kesari, S.; Wen, P. Y.] Harvard Univ, Sch Med, Div Canc Neurol, Boston, MA 02115 USA. [Norden, A. D.; Ciampa, A. S.; Ebbeling, L. G.; Levy, B.; Drappatz, J.; Kesari, S.; Wen, P. Y.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Young, G. S.; Setayesh, K.; Klufas, R.; Ross, G. L.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Muzikansky, A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA USA. RP Norden, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430B,444 Binney St, Boston, MA 02115 USA. EM anorden@partners.org RI leng, xianwei/F-9073-2011; Kesari, Santosh/E-8461-2013 NR 30 TC 499 Z9 510 U1 3 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 4 PY 2008 VL 70 IS 10 BP 779 EP 787 DI 10.1212/01.wnl.0000304121.57857.38 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 271GE UT WOS:000253776100007 PM 18316689 ER PT J AU Lee, IH Cao, L Mostoslavsky, R Lombard, DB Liu, J Bruns, NE Tsokos, M Alt, FW Finkel, T AF Lee, In Hye Cao, Liu Mostoslavsky, Raul Lombard, David B. Liu, Jie Bruns, Nicholas E. Tsokos, Maria Alt, Frederick W. Finkel, Toren TI A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION; CELL-SURVIVAL; C-ELEGANS; MICE; DISEASE; PGC-1-ALPHA; P53; NEURODEGENERATION; SIRTUINS AB We demonstrate a role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. In particular, transient increased expression of Sirt1 is sufficient to stimulate basal rates of autophagy. In addition, we show that Sirt1(-/-) mouse embryonic fibroblasts do not fully activate autophagy under starved conditions. Reconstitution with wild-type but not a deacetylase-inactive mutant of Sirt1 restores autophagy in these cells. We further demonstrate that Sirt1 can form a molecular complex with several essential components of the autophagy machinery, including autophagy genes (Atg)5, Atg7, and Atg8. In vitro, Sirt1 can, in an NAD-dependent fashion, directly deacetylate these components. The absence of Sirt1 leads to markedly elevated acetylation of proteins known to be required for autophagy in both cultured cells and in embryonic and neonatal tissues. Finally, we show that Sirt1-/- mice partially resemble Atg5(-/-) mice, including the accumulation of damaged organelles, disruption of energy homeostasis, and early perinatal mortality. Furthermore, the in utero delivery of the metabolic substrate pyruvate extends the survival of Sirt1-/- pups. These results suggest that the Sirt1 deacetylase is an important in vivo regulator of autophagy and provide a link between sirtuin function and the overall cellular response to limited nutrients. C1 [Mostoslavsky, Raul; Lombard, David B.; Alt, Frederick W.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. [Lee, In Hye; Liu, Jie; Bruns, Nicholas E.; Finkel, Toren] NHLBI, Translat Med Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. [Lombard, David B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Tsokos, Maria] Natl Canc Inst, Pathol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; tf35d@nih.gov FU Intramural NIH HHS NR 37 TC 514 Z9 542 U1 8 U2 55 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 MAR 4 PY 2008 VL 105 IS 9 BP 3374 EP 3379 DI 10.1073/pnas.0712145105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500037 PM 18296641 ER PT J AU Mani, R Onge, RPS Hartman, JL Giaever, G Roth, FP AF Mani, Ramamurthy Onge, Robert P. St. Hartman, John L. Giaever, Guri Roth, Frederick P. TI Defining genetic interaction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epistasis; fitness; gene function ID YEAST SACCHAROMYCES-CEREVISIAE; DELETERIOUS MUTATIONS; BIOLOGY; RECOMBINATION; EPISTASIS; NETWORKS; PATHWAYS; SPECTRUM; GENOME AB Sometimes mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. This phenomenon, which defines genetic interaction, can reveal functional relationships between genes and pathways. For example, double mutants with surprisingly slow growth define synergistic interactions that can identify compensatory pathways or protein complexes. Recent studies have used four mathematically distinct definitions of genetic interaction (here termed Product, Additive, Log, and Min). Whether this choice holds practical consequences has not been clear, because the definitions yield identical results under some conditions. Here, we show that the choice among alternative definitions can have profound consequences. Although 52% of known synergistic genetic interactions in Saccharomyces cerevisiae were inferred according to the Min definition, we find that both Product and Log definitions (shown here to be practically equivalent) are better than Min for identifying functional relationships. Additionally, we show that the Additive and Log definitions, each commonly used in population genetics, lead to differing conclusions related to the selective advantages of sexual reproduction. C1 [Mani, Ramamurthy; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Onge, Robert P. St.] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. [Hartman, John L.] Univ Alabama, Dept Genet, Birmingham, AL 35294 USA. [Giaever, Guri] Univ Toronto, Leslie Dan Fac Pharm, Donnelly Ctr Cellular & Biomol Res, Dept Pharmaceut Sci, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. EM fritz.roth@hms.harvard.edu RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NHGRI NIH HHS [HG003224, HG003317, P50 HG004233, R01 HG003224, R01 HG003224-01A2, R01 HG003224-02, R01 HG003224-03, R01 HG003317]; NIDDK NIH HHS [DK056336, P30 DK056336] NR 30 TC 181 Z9 183 U1 1 U2 9 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 MAR 4 PY 2008 VL 105 IS 9 BP 3461 EP 3466 DI 10.1073/pnas.0712255105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500052 PM 18305163 ER PT J AU Verginis, P McLaughlin, KA Wucherpfennig, KW von Boehmer, H Apostolou, I AF Verginis, Panayotis McLaughlin, Katherine A. Wucherpfennig, Kai W. von Boehmer, Harald Apostolou, Irina TI Induction of antigen-specific regulatory T cells in wild-type mice: Visualization and targets of suppression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Foxp3; induction of tolerance; transplantation tolerance ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; RECEPTOR TRANSGENIC MICE; IN-VIVO; DENDRITIC CELLS; TOLERANCE; GENERATION; REJECTION; PEPTIDES; EXPOSURE AB Antigen-specific transplantation tolerance in the absence of immunosuppressive drugs is a rarely achieved goal. Immune responses to Y chromosome-encoded transplantation antigens (HY) can have life-threatening consequences in the clinic. Here, we have adopted a procedure developed in T cell antigen receptor (TCR)-transgenic mice to convert naive T cells into male-specific Foxp3(+) regulatory T cells (Tregs) in WT female mice. For this purpose, female mice were infused by osmotic minipumps with a single class II MHC-presented HY peptide and Tregs visualized by tetramer staining. As a result, animals developed Treg-mediated long-term tolerance to all HY transplantation antigens, irrespective of whether they were recognized by CD4 or CD8 T cells, on skin or hematopoietic grafts from male donors. C1 [Verginis, Panayotis; McLaughlin, Katherine A.; Wucherpfennig, Kai W.; von Boehmer, Harald; Apostolou, Irina] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Verginis, Panayotis; von Boehmer, Harald; Apostolou, Irina] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [McLaughlin, Katherine A.; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Apostolou, I (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM irina_apostolou@dfci.harvard.edu FU NIAID NIH HHS [R01 AI057493, P01 AI045757]; PHS HHS [R37 53102] NR 29 TC 61 Z9 64 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2008 VL 105 IS 9 BP 3479 EP 3484 DI 10.1073/pnas.0800149105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500055 PM 18299571 ER PT J AU Emanuelli, B Eberle, D Suzuki, R Kahn, CR AF Emanuelli, Brice Eberle, Delphine Suzuki, Ryo Kahn, C. Ronald TI Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokines; diabetes; kinases; obesity ID NECROSIS-FACTOR-ALPHA; STIMULATED GLUCOSE-UPTAKE; 3T3-L1 ADIPOCYTES; KINASE PHOSPHATASE; TYROSINE-PHOSPHATASE; RECEPTOR SUBSTRATE-1; POTENTIAL ROLE; ACTIVATION; JNK; GLUT4 AB Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process. We found that MKP-4 expression is up-regulated during adipocyte and myocyte differentiation in vitro and up-regulated during fasting in white adipose tissue in vivo. Overexpression of MKP-4 in 3T3-L1 cells inhibited ERK and JNK phosphorylation and, to a lesser extent, p38MAPK phosphorylation. As a result, the phosphorylation of IRS-1 serine 307 induced by anisomycin was abolished, leading to a sensitization of insulin signaling with recovery of insulin-stimulated IRS-1 tyrosine phosphorylation, IRS-1 docking with phosphatidylinositol 3-kinase, and Akt phosphorylation. MKP-4 also reversed the effect of TNF-alpha to inhibit insulin signaling; alter IL-6, GIut1 and GIut4 expression; and inhibit insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Overexpression of MKP-4 in the liver of ob/ob mice decreased ERK and JNK phosphorylation, leading to a reduction in fed and fasted glycemia, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders. C1 [Emanuelli, Brice; Eberle, Delphine; Suzuki, Ryo; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Emanuelli, Brice/M-2097-2016 FU NIDDK NIH HHS [DK33201, R01 DK033201] NR 33 TC 44 Z9 49 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2008 VL 105 IS 9 BP 3545 EP 3550 DI 10.1073/pnas.0712275105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500066 PM 18296638 ER PT J AU Goldberg, RF Austen, WG Zhang, XB Munene, G Mostafa, G Biswas, S McCormack, M Eberlin, KR Nguyen, JT Tatlidede, HS Warren, HS Narisawa, S Millan, JL Hodin, RA AF Goldberg, Ross F. Austen, William G., Jr. Zhang, Xiaobo Munene, Gitonga Mostafa, Golam Biswas, Shaluk McCormack, Michael Eberlin, Kyle R. Nguyen, John T. Tatlidede, Hamit S. Warren, H. Shaw Narisawa, Sonoko Millan, Jose L. Hodin, Richard A. TI Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gut barrier; lipopolysaccharide; trophic feeding; bacterial translocation; NF-kappa B ID MULTIPLE-ORGAN-FAILURE; GENE-EXPRESSION; GASTROINTESTINAL-TRACT; EPITHELIAL BARRIER; GROWTH-STATE; BRUSH-BORDER; ENTEROCYTE; ISCHEMIA; INJURY; CIRCULATION AB Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush-border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients. C1 [Goldberg, Ross F.; Austen, William G., Jr.; Zhang, Xiaobo; Munene, Gitonga; Mostafa, Golam; Biswas, Shaluk; McCormack, Michael; Eberlin, Kyle R.; Nguyen, John T.; Tatlidede, Hamit S.; Hodin, Richard A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Warren, H. Shaw] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Narisawa, Sonoko; Millan, Jose L.] Burnham Inst Med Res, La Jolla, CA 92037 USA. RP Hodin, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. EM rhodin@partners.org RI Millan, Jose Luis/B-6580-2008 FU NIDDK NIH HHS [DK47186, DK50623, R01 DK047186, R01 DK050623] NR 39 TC 154 Z9 162 U1 4 U2 20 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 MAR 4 PY 2008 VL 105 IS 9 BP 3551 EP 3556 DI 10.1073/pnas.0712140105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500067 PM 18292227 ER PT J AU Tootell, RBH Devaney, KJ Young, JC Postelnicu, G Rajimehr, R Ungerleider, LG AF Tootell, Roger B. H. Devaney, Kathryn J. Young, Jeremy C. Postelnicu, Gheorghe Rajimehr, Reza Ungerleider, Leslie G. TI fMRI mapping of a morphed continuum of 3D shapes within inferior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE category; continuous; single-stimulus ID MONKEY INFEROTEMPORAL CORTEX; SURFACE-BASED ANALYSIS; FUSIFORM FACE AREA; VISUAL PROPERTIES; FUNCTIONAL-ORGANIZATION; NONHUMAN-PRIMATES; SELECTIVE CELLS; MACAQUE; OBJECTS; NEURONS AB Here, we mapped fMRI responses to incrementally changing shapes along a continuous 3D morph, ranging from a head ("face") to a house ("place"). The response to each shape was mapped independently by using single-stimulus imaging, and stimulus shapes were equated for lower-level visual cues. We measured activity in 2-mm samples across human inferior temporal cortex from the fusiform face area (FFA) (apparently selective for faces) to the parahippocampal place area (PPA) (apparently selective for places), testing for (i) incremental changes in the topography of FFA and PPA (predicted by the continuous-mapping model) or (ii) little or no response to the intermediate morphed shapes (predicted by the category model). Neither result occurred; instead, we found approximately linearly graded changes in the response amplitudes to graded-shape changes, without changes in topography-similar to visual responses in different lower-tier cortical areas. C1 [Tootell, Roger B. H.; Devaney, Kathryn J.; Young, Jeremy C.; Postelnicu, Gheorghe; Rajimehr, Reza] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tootell, Roger B. H.] NIMH, Lab Brain Cognit, Bethesda, MD 20892 USA. [Tootell, Roger B. H.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tootell, RBH (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM tootell@nmr.mgh.harvard.edu FU Intramural NIH HHS; NCRR NIH HHS [P41 RR014075, P41 RR14075]; NEI NIH HHS [R01 EY017081, R01 EY017081-01A1, R01 EY017081-02, R01 EY017081-03]; NIMH NIH HHS [R01 MH67529, R01 MH067529] NR 40 TC 18 Z9 18 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2008 VL 105 IS 9 BP 3605 EP 3609 DI 10.1073/pnas.0712274105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 272FY UT WOS:000253846500076 PM 18287004 ER PT J AU Williams, KN Ramani, S Fraser, B Orlander, JD AF Williams, Keith N. Ramani, Subha Fraser, Bruce Orlander, Jay D. TI Improving Bedside Teaching: Findings from a Focus Group Study of Learners SO ACADEMIC MEDICINE LA English DT Article ID ATTENDING ROUNDS; CLINICAL-EXPERIENCE; PATIENT; PHYSICIAN; MEDICINE; WARDS; TIME AB Purpose Literature reviews indicate that the proportion of clinical educational time devoted to bedside teaching ranges from 8% to 19%. Previous studies regarding this paucity have not adequately examined the perspectives of learners. The authors explored learners' attitudes toward bedside teaching, perceptions of barriers, and strategies to increase its frequency and effectiveness, as well as whether learners' stages of training influenced their perspectives. Method Six focus group discussions with fourth-year medical students and first- or second-year internal medicine residents recruited from the Boston University School of Medicine and Residency Program in Internal Medicine were conducted between June 2004 and February 2005, Each 60- to 90-minute discussion was audiotaped, transcribed and analyzed using qualitative methods. Results Learners believed that bedside teaching is valuable for learning essential clinical skills. They believed it is underutilized and described many barriers to its use: lack of respect for the patient, time constraints; learner autonomy; faculty attitude, knowledge, and skill; and overreliance on technology. Learners suggested a variety of strategies to mitigate barriers: orienting and including the patient; addressing time constraints through flexibility, selectivity, and integration with work; providing learners with reassurance, reinforcing their autonomy, and incorporating them into the teaching process; faculty development; and advocating evidence-based physical diagnosis. Students focused on the physical diagnosis aspects of bedside teaching, whereas views of residents reflected their multifaceted roles as learners, teachers, and managers. Conclusions Bedside teaching is valuable but underutilized. Including the patient, collaborating with learners, faculty development, and promoting a supportive institutional culture can redress several barriers to bedside teaching. C1 [Ramani, Subha] Boston Univ, Sch Med, Internal Med Residency Program, Boston, MA 02118 USA. [Fraser, Bruce] Boston Univ, Appl Linguist Program, Boston, MA 02118 USA. [Fraser, Bruce] Boston Univ, Sch Educ, Boston, MA 02118 USA. [Orlander, Jay D.] VA Boston Hlth Care Syst, Boston, MA USA. RP Ramani, S (reprint author), Boston Univ, Sch Med, Internal Med Residency Program, 715 Albany St,Vose 320, Boston, MA 02118 USA. EM Keith.Williams@bmc.org FU HRSA Faculty Development Training [D55HP00215] FX This research was supported in part by the HRSA Faculty Development Training Grant #D55HP00215. NR 46 TC 52 Z9 52 U1 1 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 2008 VL 83 IS 3 BP 257 EP 264 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466ID UT WOS:000267653900008 PM 18316871 ER PT J AU Andersen, CB Wan, Y Chang, JW Riggs, B Lee, C Liu, Y Sessa, F Villa, F Kwiatkowski, N Suzuki, M Nallan, L Heald, R Musacchio, A Gray, NS AF Andersen, Carsten B. Wan, Yongqin Chang, Jae W. Riggs, Blake Lee, Christian Liu, Yi Sessa, Fabio Villa, Fabrizio Kwiatkowski, Nicholas Suzuki, Melissa Nallan, Laxman Heald, Rebecca Musacchio, Andrea Gray, Nathanael S. TI Discovery of selective aminothiazole aurora kinase inhibitors SO ACS CHEMICAL BIOLOGY LA English DT Article ID A KINASE; PROTEIN-KINASE; B KINASE; IN-VIVO; SPINDLE; DROSOPHILA; POTENT; YEAST; PHOSPHORYLATION; PROGRESSION AB Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 angstrom cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication. C1 [Chang, Jae W.; Kwiatkowski, Nicholas; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol,Dept Canc Biol, Boston, MA 02115 USA. [Andersen, Carsten B.; Wan, Yongqin; Lee, Christian; Liu, Yi; Nallan, Laxman] Novartis Res Fdn, Gen Inst, Dept Biol Chem, San Diego, CA 92121 USA. [Sessa, Fabio; Villa, Fabrizio; Musacchio, Andrea] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy. [Riggs, Blake; Heald, Rebecca] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Suzuki, Melissa] Invitrogen Corp, Madison, WI 53558 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol,Dept Canc Biol, 250 Longwood Ave, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu RI villa, fabrizio/G-5757-2012; OI Musacchio, Andrea/0000-0003-2362-8784; Heald, Rebecca/0000-0001-6671-6528 NR 48 TC 23 Z9 23 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD MAR PY 2008 VL 3 IS 3 BP 180 EP 192 DI 10.1021/cb700200w PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277ND UT WOS:000254218800007 PM 18307303 ER PT J AU Valaskatgis, P Macklin, EA Schachter, SC Wayne, PM AF Valaskatgis, Peter Macklin, Eric A. Schachter, Steven C. Wayne, Peter M. TI Possible effects of acupuncture on atrial fibrillation and post-herpetic neuralgia - a case report SO ACUPUNCTURE IN MEDICINE LA English DT Editorial Material DE Acupuncture; post-herpetic neuralgia; pain; herpes zoster; atrial fibrillation; cardiac arrhythmias; palpitations ID ISCHEMIA; RATS AB A 72 year old female with a main complaint of severe post-herpetic neuralgia and a secondary complaint of atrial fibrillation (AF) received two series of acupuncture treatments totalling 20 treatments over a four month period. Her standard medical treatment remained unchanged. The primary focus of the acupuncture was pain relief; however, two acupuncture points (PC6, SP4) were included in both treatment series because of possible effects on both costal or chest pain and cardiac arrhythmias, according to Traditional Chinese Medicine (TCM) teaching and limited research. As recorded by her pacemaker, estimated weekly episodes of AF in the patient decreased significantly, and percentage time in AF decreased with borderline statistical significance, from the pretreatment estimates during the second series of treatments (weekly AF episode estimates: pretreatment =71.4; second series =16.5, difference estimates =-54.9, 95% CI -6.5 to -103.3, P=0.02; percentage time in AF estimates: pretreatment =30.6; 2 second series =18.0, difference estimates =-12.6, 95% CI 0.9 to -26.0, P=0.08). The pain levels were also significantly reduced following the acupuncture treatment series by more than 67%. Further studies are warranted to further explore these observations of a possible effect of acupuncture on both atrial fibrillation and post-herpetic neuralgia. C1 [Valaskatgis, Peter] New England Sch Acupuncture, Newton, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schachter, Steven C.; Wayne, Peter M.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. RP Valaskatgis, P (reprint author), New England Sch Acupuncture, Newton, MA USA. EM peterval@comcast.net RI Macklin, Eric/E-2955-2013; cmu, library/L-1810-2013 OI Macklin, Eric/0000-0003-1618-3502; FU National Center for Complementary and Alternative Medicine (NCCAM) [5 U19 AT002022-02] FX This study was supported by Grant # 5 U19 AT002022-02 from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, or the National Institutes of Health. The New England School of Acupuncture Institutional Review Board approved this study. The authors thank the following colleagues for their feedback and suggestions: Jacqueline Carrol, Dan Eyink, Evelyn Fowler, Li Gaudet, Amy Hull, Mary Kahn, Edvardas Kaminskas, Giovanni Maciocia, John McLaulin, John Miller, Monica Shields, Linda Valaskatgis. NR 20 TC 0 Z9 1 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-5284 J9 ACUPUNCT MED JI Acupunct. Med. PD MAR PY 2008 VL 26 IS 1 BP 51 EP 56 DI 10.1136/aim.26.1.51 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V13LT UT WOS:000207669000007 PM 18356799 ER PT J AU Mantione, KJ Cadet, P Zhu, W Kream, RM Sheehan, M Fricchione, GL Goumon, Y Esch, T Stefano, GB AF Mantione, Kirk J. Cadet, Patrick Zhu, Wei Kream, Richard M. Sheehan, Melinda Fricchione, Gregory L. Goumon, Yannick Esch, Tobias Stefano, George B. TI Endogenous morphine signaling via nitric oxide regulates the expression of CYP2D6 and COMT: autocrine/paracrine feedback inhibition SO ADDICTION BIOLOGY LA English DT Article DE COMT; CYP2D6; microarray; morphine; nitric oxide; tyrosine hydroxylase ID MU(3) OPIATE RECEPTOR; TYROSINE-HYDROXYLASE; ENDOTHELIAL-CELLS; MEDIAN-EMINENCE; GENE; RAT; IDENTIFICATION; BIOSYNTHESIS; INVERTEBRATE; IMMUNOCYTES AB We determined changes in mRNA expression in specific enzymes involved in the biosynthesis of morphine in human white blood cells via microarray. Leukocyte exposure to morphine down-regulated catechol-O-methyl transferase (COMT) and CYP2D6 by approximately 50% compared with control values. The treatment did not alter DOPA decarboxylase and dopamine beta-hydroxylase expression, demonstrating the specificity of morphine actions. The verification of the microarray data was accomplished via real-time Taqman reverse transcriptase polymerase chain reaction (RT-PCR) focused on CYP2D6 and COMT expression in different blood samples treated with morphine. The analysis showed similar changes in the expression of CYP2D6 and COMT mRNA. The expression was reduced by 47 +/- 7% for CYP2D6, substantiating the microarray finding of a 54% reduction. Furthermore, exposure of white blood cells to 10(-6) M S-nitroso-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, reduced the expression of CYP2D6 and COMT. Prior naloxone (10(-6) M) or N-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) addition abrogated morphine's down-regulating activity, demonstrating morphine was initiating its actions via stimulating constitutive NO synthase derived NO release via the mu(3) opiate receptor splice variant. In the past we demonstrated that UDP-glucurosyltransferase is involved in metabolizing morphine to morphine 6-glucuronide in adrenal chromaffin cells. In the present study its expression was not found in controls and morphine-treated cells, suggesting that morphine 6-glucuronide may not be synthesized in white blood cells. Taken together, it appears that morphine has the ability to modulate its own synthesis via autocrine and paracrine signaling. C1 [Mantione, Kirk J.; Cadet, Patrick; Zhu, Wei; Sheehan, Melinda; Stefano, George B.] SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. [Kream, Richard M.] SUNY Hlth Sci Ctr, Dept Biochem, New York, NY USA. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Goumon, Yannick] INSERM, HDR, CRI, U 575, F-75654 Paris, France. [Esch, Tobias] Coburg Univ Appl Sci, Div Integrat Hlth Promot, Coburg, Germany. RP Stefano, GB (reprint author), SUNY Coll Old Westbury, Neurosci Res Inst, PO Box 210, Old Westbury, NY 11568 USA. EM gstefano@sunynri.org RI Esch, Tobias/J-3812-2013; OI Esch, Tobias/0000-0001-5176-4367; Mantione, Kirk/0000-0001-5822-8946 NR 30 TC 24 Z9 25 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2008 VL 13 IS 1 BP 118 EP 123 DI 10.1111/j.1369-1600.2007.00072.x PG 6 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 259GN UT WOS:000252927900014 PM 17573783 ER PT J AU Johnson, SC Schmitz, TW Asthana, S Gluck, MA Myers, C AF Johnson, Sterling C. Schmitz, Taylor W. Asthana, Sanjay Gluck, Mark A. Myers, Catherine TI Associative learning over trials activates the hippocampus in healthy elderly but not mild cognitive impairment SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article ID MEDIAL TEMPORAL-LOBE; ALZHEIMERS-DISEASE; DECLARATIVE MEMORY; ATROPHY; FMRI; AD; REPETITION; RETRIEVAL; DECLINE; CORTEX AB The ability to form associations between choice alternatives and their contingent outcomes is an important aspect of learning that may be sensitive to hippocampal dysfunction in memory disorders of aging such as amnestic mild cognitive impairment (MCIa), or early Alzheimer disease. In this preliminary study we examined brain activation using functional magnetic resonance imaging (fMRI) in 12 healthy elderly participants and nine patients with MCIa during an associative learning task. Using a high-field 3.0-Tesla MRI scanner, we examined the dynamic neural response during associative learning over trials. The slope of signal attenuation associated with learning was analyzed for differences between groups within an a priori defined hippocampal region. Results indicated dynamic signal attenuation associated with learning in the healthy elderly sample, but not in MCIa. The absence of an associative learning effect in the MCIa sample reaffirms an important link between the learning difficulties that are commonly encountered in MCIa and the mesial temporal region. C1 [Johnson, Sterling C.; Schmitz, Taylor W.; Asthana, Sanjay] Wm S Middleton VA Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Johnson, Sterling C.; Schmitz, Taylor W.; Asthana, Sanjay] Univ Wisconsin, Sch Med, Madison, WI USA. [Gluck, Mark A.; Myers, Catherine] Rutgers State Univ, Newark, NJ 07102 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Myers, Catherine/0000-0002-2776-4823 NR 51 TC 23 Z9 23 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD MAR PY 2008 VL 15 IS 2 BP 129 EP 145 DI 10.1080/13825580601139444 PG 17 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 270OP UT WOS:000253730400001 ER PT J AU Manrique, M Micewicz, E Kozlowski, PA Wang, SW Aurora, D Wilson, RL Ghebremichael, M Mazzara, G Montefiori, D Carville, A Mansfield, KG Aldovini, A AF Manrique, Mariana Micewicz, Ewa Kozlowski, Pamela A. Wang, Shainn-Wei Aurora, Deepti Wilson, Robert L. Ghebremichael, Musie Mazzara, Gail Montefiori, David Carville, Angela Mansfield, Keith G. Aldovini, Anna TI DNA-MVA vaccine protection after x4 SHIV challenge in Macaques correlates with day-of-challenge antiviral CD4(+) cell-mediated immunity levels and postchallenge preservation of CD4(+) T cell memory SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; POLYMERASE CHAIN-REACTION; LYMPH-NODE IMMUNIZATION; RHESUS MACAQUES; DENDRITIC CELLS; GASTROINTESTINAL-TRACT; ANTIBODY-RESPONSES; MUCOSAL IMMUNITY; TYPE-1 INFECTION; SECRETING CELLS AB The ability of vaccines to induce immunity both in mucosal and systemic compartments may be required for prevention of HIV infection and AIDS. We compared DNA-MVA vaccination regimens adjuvanted by IL-12 DNA, administered intramuscularly and nasally or only nasally. Most of the vaccinated Rhesus macaques developed mucosal and systemic humoral and cell-mediated SHIV-specific immune responses. Stimulation of mucosal anti-Env IgA responses was limited. After rectal challenge with SHIV 89.6P, all vaccinated and naive animals became infected. However, most of the vaccinated animals showed significant control of viremia and protection from CD4(+) T cell loss and AIDS progression compared to the control animals. The levels of CD4(+) and CD8(+) T cell virus-specific responses measured on the day of challenge correlated with the level of viremia control observed later during the chronic infection. Postchallenge viremia levels inversely correlated with the preservation of SHIV-specific CD4(+)/IL-2(+) and CD8(+)/ TNF-alpha(+) T cells but not with CD4(+)/IFN-gamma(+) T cells measured over time after challenge. We also found that during the early chronic infection SHIV vaccination permitted a more significant preservation of both naive and memory CD4(+) T cells compared to controls. In addition, we observed a more significant and prolonged preservation of memory CD4(+) T cells after SHIV vaccination and challenge than that observed after SIV vaccination and challenge. As the antiviral immunity stimulated by vaccination is present in the memory CD4(+) T cell subpopulations, its more limited targeting by SHIV compared to SIV may explain the better control of X4 tropic SHIV than R5 tropic SIVs by vaccination. C1 [Manrique, Mariana; Micewicz, Ewa; Kozlowski, Pamela A.; Wang, Shainn-Wei; Aurora, Deepti; Wilson, Robert L.; Aldovini, Anna] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Manrique, Mariana; Micewicz, Ewa; Kozlowski, Pamela A.; Wang, Shainn-Wei; Aurora, Deepti; Wilson, Robert L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ghebremichael, Musie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mazzara, Gail] Therion Biol, Cambridge, MA 02142 USA. [Montefiori, David] Duke Univ, Durham, NC 27706 USA. [Carville, Angela; Mansfield, Keith G.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. RP Aldovini, A (reprint author), Childrens Hosp, Dept Med, Enders 861,300 Longwood Ave, Boston, MA 02115 USA. EM anna.aldovini@childrens.harvard.edu RI Manrique, Mariana/D-4165-2013 OI Manrique, Mariana/0000-0003-1004-8158 FU NCI NIH HHS [N01-CO-124000]; NIAID NIH HHS [5P30AI060354, R21 AI048133, AI48133, R01 AI058896-04, R56 AI041365, P30 AI060354, AI41365, R01 AI041365] NR 63 TC 24 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 MAR PY 2008 VL 24 IS 3 BP 505 EP 519 DI 10.1089/aid.2007.0191 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 284VP UT WOS:000254735200021 PM 18373436 ER PT J AU Walker, BM Rasmussen, DD Raskind, MA Koob, GF AF Walker, Brendan M. Rasmussen, Dennis D. Raskind, Murray A. Koob, George F. TI alpha(1)-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol SO ALCOHOL LA English DT Article DE ethanol; reinforcement; dependence; withdrawal; norepinephrine; noradrenaline ID POSITIVE REINFORCING PROPERTIES; CORTICOTROPIN-RELEASING-FACTOR; DOPAMINE-BETA-HYDROXYLASE; OPIATE WITHDRAWAL; PHARMACOLOGICAL EVIDENCE; NORADRENERGIC MEDIATION; DRINKING BEHAVIOR; STRIA TERMINALIS; LABORATORY RATS; BED NUCLEUS AB The purpose of this study was to test the hypothesis that blockade of alpha(1)-adrenergic receptors may suppress the excessive ethanol consumption associated with acute withdrawal in ethanol-dependent rats. Following the acquisition and stabilization of operant ethanol self-administration in male Wistar rats, dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 h/day. Subsequent to dependence induction, the effect of alpha(1)-noradrenergic receptor antagonist prazosin (0.0, 0.25, 0.5, 1, 1.5, and 2.0 mg/kg IP) was tested on operant responding for ethanol in vapor-exposed and control rats during acute withdrawal. In ethanol-dependent animals, prazosin significantly suppressed responding at the 1.5 and 2.0 mg/kg doses, whereas only the 2.0 mg/kg dose was effective in nondependent animals, identifying an increase in the sensitivity to prazosin in dependent animals. Conversely, at the lowest dose tested (0.25 mg/kg), prazosin increased responding in nondependent animals, which is consistent with the effect of anxiolytics on ethanol self-administration in nondependent animals. None of the doses tested reliably affected concurrent water self-administration. These results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats. (C) 2008 Elsevier Inc. All rights reserved. C1 [Walker, Brendan M.] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Walker, Brendan M.; Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Rasmussen, Dennis D.; Raskind, Murray A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Rasmussen, Dennis D.; Raskind, Murray A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Walker, BM (reprint author), Scripps Res Inst, Mol & Integrat Neurosci Dept, 10550 N Torrey Pines Rd,SP30-1501, La Jolla, CA 92037 USA. EM bwalker@scripps.edu RI Walker, Brendan /B-9219-2011; koob, george/P-8791-2016 OI Walker, Brendan /0000-0002-7217-3950; FU NIAAA NIH HHS [AA012602, AA014723, F32 AA014723, F32 AA014723-01, F32 AA014723-02, F32 AA014723-03, R01 AA012602] NR 39 TC 83 Z9 83 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAR PY 2008 VL 42 IS 2 BP 91 EP 97 DI 10.1016/j.alcohol.2007.12.002 PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 282UP UT WOS:000254593000004 PM 18358987 ER PT J AU Alhomsi, K Selig, M Sustic, T Katrangi, E Weissig, V Laposata, M AF Alhomsi, Khaled Selig, Martin Sustic, Tonci Katrangi, Eyad Weissig, Volkmar Laposata, Michael TI Induction of apoptosis and necrosis in human peripheral blood mononuclear cells by fatty acid ethyl esters SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE human mononuclear cells; fatty acid ethyl esters; ethyl oleate; ethanol; DNA degradation; apoptosis; necrosis; lactate dehydrogenase; free fatty acid; immunity; PARP cleavage ID HUMAN SERUM; ETHANOL; ALCOHOL; METABOLITES; LYMPHOPENIA; ABUSE; DEATH AB Background: Fatty acid ethyl esters (FAEE), nonoxidative products of ethanol metabolism, are formed by the esterification of fatty acids and ethanol. Alcoholic subjects have high levels of FAEE in the circulation as well as in organs and tissues, especially those most often damaged by ethanol abuse. Our previous studies showed a significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. In addition, FAEE inhibited phytohemagglutinin (PHA)-stimulated interleukin-2 production and calcium (Ca2+) influx into human mononuclear cells. FAEE also caused a rapid increase in the intracellular cAMP. The mechanism by which alcohol suppresses the immune system remains undetermined. Objectives: To evaluate the morphological and physiological effects of FAEE on human mononuclear cells and to study the impact of FAEE on cell viability. Methods: Mononuclear cell fractions of human white blood cells (WBC) were incubated with physiological doses (25 and 50 mu M) of ethyl oleate, a representative FAEE, for 15, 30, 60, 120 or 180 minutes. Morphological changes were evaluated by light and transmission electron microscopy (TEM). Lactate dehydrogenase (LDH) release was measured as a physiological indicator of necrosis. Physiological changes were also evaluated by western blots performed on whole-cell lysates of treated and untreated cells and by DNA electrophoresis. Results: Significant morphological changes were detected in cells exposed to FAEE by both light and TEM. Concentration and time-dependent increases in the rates of apoptosis and necrosis were found by light microscopy and by LDH release, respectively, following 60 minutes exposure to 25 or 50 mu M FAEE. One-hour 50 mu M FAEE exposure caused activation of the caspase cascade, as demonstrated by Poly (ADP-ribose) Polymerase (PARP) cleavage, and significant DNA damage as a result of necrosis in human mononuclear cells. Conclusions: These studies provide evidence to support the toxic effects of FAEE on intact human mononuclear cells. The results from our studies also show that both apoptosis and necrosis are modes of cell death in FAEE-treated human mononuclear cells. This may be an important mechanism in alcohol-induced immunosuppression. C1 [Alhomsi, Khaled; Selig, Martin; Laposata, Michael] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Alhomsi, Khaled; Selig, Martin; Laposata, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Sustic, Tonci] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Sustic, Tonci] Harvard Univ, Sch Med, Charlestown, MA USA. [Katrangi, Eyad; Weissig, Volkmar] Northeastern Univ, Dept Pharmaceut Sci, Bouve Coll Pharm & Hlth Sci, Boston, MA 02115 USA. RP Alhomsi, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 31 TC 6 Z9 7 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2008 VL 32 IS 3 BP 534 EP 543 DI 10.1111/j.1530-0277.2007.00597.x PG 10 WC Substance Abuse SC Substance Abuse GA 267II UT WOS:000253502300020 PM 18215210 ER PT J AU Gaziano, JM AF Gaziano, J. Michael TI Marijuana use among those at risk for cardiovascular events SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID CANNABIS; SMOKING C1 [Gaziano, J. Michael] VA Boston Hlth Care Syst, Massachusetts Epidemiol & Informat Ctr MAVERIC, Boston, MA USA. [Gaziano, J. Michael] VA Boston Hlth Care Syst, GRECC, Boston, MA USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc Dis & Prevent Med, Boston, MA USA. RP Gaziano, JM (reprint author), VA Boston Hlth Care Syst, Massachusetts Epidemiol & Informat Ctr MAVERIC, Boston, MA USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2008 VL 155 IS 3 BP 395 EP 396 DI 10.1016/j.ahj.2007.12.016 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 271OO UT WOS:000253798100001 PM 18294471 ER PT J AU Mukamal, KJ Maclure, M Muller, JE Mittleman, MA AF Mukamal, Kenneth J. Maclure, Malcolm Muller, James E. Mittleman, Murray A. TI An exploratory prospective study of marijuana use and mortality following acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID HUMAN RISK-TAKING; SMOKING MARIHUANA; CANNABIS; CONSUMPTION; HOSPITALIZATION; HEALTH; DEATH; MEN AB Background The relationship of marijuana use with coronary heart disease, including prognosis among patients with coronary heart disease, is uncertain. Methods We conducted an inception cohort study of 1913 adults hospitalized with myocardial infarction at 45 US hospitals between 1989 and 1994, with a median follow-up of 3.8 years. We ascertained total mortality according to self-reported marijuana use in the preceding year. Results A total of 52 patients reported marijuana use during the prior year, and 3 17 patients died during follow-up. Compared with nonuse, marijuana use less than weekly was associated with a hazard ratio of 2.5 (95, % CI, 0.9-7.3). The corresponding hazard ratio for weekly use or more was 4.2 (95% CI, 1.2-14.3). The age- and sex-adjusted hazard ratios associated with any use were 1.9 (95% CI, 0.6-6.3) for cardiovascular mortality and 4.9 (95% CI, 1.6-14.7) for noncardiovascular mortality. In a comparison of 42 marijuana users and 42 other patients matched on propensity scores, there were 6 deaths among marijuana users and one among non-users (log-rank P = .06). Conclusions These preliminary results suggest possible hazards of marijuana for patients who survive acute myocardial infarction. Although marijuana use has not been associated with mortality in other populations, it may pose particular risk for susceptible individuals with coronary heart disease. C1 [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Div Cardiol, Brookline, MA 02446 USA. [Maclure, Malcolm; Mittleman, Murray A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Muller, James E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu FU NHLBI NIH HHS [R01 HL041016, R01 HL041016-09A1, R01HL41016]; NIAAA NIH HHS [R21 AA014900, R21 AA014900-02, R21AA014900] NR 38 TC 54 Z9 55 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2008 VL 155 IS 3 BP 465 EP 470 DI 10.1016/j.ahj.2007.10.049 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 271OO UT WOS:000253798100008 PM 18294478 ER PT J AU Tricomi, AJ Magid, DJ Rumsfeld, JS Vinson, DR Lyons, EE Crounse, L Ho, PM Peterson, PN Masoudi, FA AF Tricomi, Albert J. Magid, David J. Rumsfeld, John S. Vinson, David R. Lyons, Ella E. Crounse, Laurie Ho, P. Michael Peterson, Pamela N. Masoudi, Frederick A. CA EDQMI Study Investigators TI Missed opportunities for reperfusion therapy for ST-segment elevation myocardial infarction: Results of the Emergency Department Ouality in Myocardial Infarction (EDOMI) study SO AMERICAN HEART JOURNAL LA English DT Article ID BUNDLE-BRANCH BLOCK; THROMBOLYTIC THERAPY; MULTICENTER; MORTALITY; REGISTRY AB Background Although it is known that reperfusion therapy for ST-elevation myocardial infarction (STEMI) is underused, the reasons for the failure to provide this potentially life-saving treatment are not well described. Methods In a cohort of 2215 consecutive patients presenting with acute myocardial infarction to 5 emergency departments in Colorado and California between 2000 and 2002, patients with ischemic symptoms and ST-segment elevation on electrocardiogram without documented guideline-based contraindications to therapy were identified as eligible reperfusion candidates. Multivariable logistic models were constructed to identify factors associated with the failure to receive reperfusion. The emergency department records of patients not receiving reperfusion were reviewed to categorize the reasons therapy was not provided. Results Of 460 eligible patients, 102 (22%) did not receive reperfusion therapy. Patient factors associated with failure to receive reperfusion therapy included older age, peripheral vascular disease, and absence of chest pain; patients seen by both resident and attending physicians were more likely to receive treatment than those seen by an attending alone. In cases where reperfusion was not provided, ST-segment elevation was not identified in 34% (n = 35), left bundle-branch block was not considered as an indication in 13% (n = 13), there was documentation of a reason for withholding therapy not supported by guidelines in 34% (n = 35), and there was no documentation of reasons for withholding reperfusion in 19% (n = 19). Conclusions Initiatives to improve electrocardiogram interpretation and evidence-based patient selection may reduce gaps in the delivery of reperfusion therapy to eligible candidates and thereby potentially improve STEMI outcomes. C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO 80204 USA. [Tricomi, Albert J.] Univ Rochester, Sch Med, Rochester, NY USA. [Magid, David J.; Rumsfeld, John S.; Lyons, Ella E.; Crounse, Laurie; Ho, P. Michael; Peterson, Pamela N.; Masoudi, Frederick A.] Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. [Magid, David J.; Rumsfeld, John S.; Ho, P. Michael; Peterson, Pamela N.; Masoudi, Frederick A.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. [Rumsfeld, John S.; Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Vinson, David R.] Kaiser Permanente Med Ctr, Roseville, CA USA. [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. RP Masoudi, FA (reprint author), Denver Hlth Med Ctr, MC0960,777 Bannock St, Denver, CO 80204 USA. EM fred.masoudi@uchsc.edu NR 14 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2008 VL 155 IS 3 BP 471 EP 477 DI 10.1016/j.ahj.2007.10.023 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 271OO UT WOS:000253798100009 PM 18294479 ER PT J AU Qureshi, WA Wu, J DeMarco, D Abudayyeh, S Graham, DY AF Qureshi, Waqar A. Wu, Justin DeMarco, Daniel Abudayyeh, Suhaib Graham, David Y. TI Capsule Endoscopy for Screening for Short-Segment Barrett's Esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CONVENTIONAL UPPER ENDOSCOPY; GASTROESOPHAGEAL-REFLUX; ADENOCARCINOMA; RISK; SURVEILLANCE; DIAGNOSIS; CANCER; POPULATION; PREVALENCE; ACCURACY AB BACKGROUND: The rise in the incidence of esophageal adenocarcinoma has led to the development of new methods to screen for the precursor lesion, Barrett's esophagus. AIM: To evaluate the potential role of esophageal capsule endoscopy in identifying the presence of short-segment Barrett's esophagus. METHODS: Patients with biopsy-proven short-segment Barrett's esophagus underwent esophageal capsule endoscopy. The images were reviewed by two expert observers with no knowledge of the purpose of the study. The data collected included transit time, quality of image, presence or absence of Z-line, Schatzki's ring, hiatal hernia, and Barrett's esophagus (long or short, definite or suspected). RESULTS: Twenty patients were studied; in 18, the capsule passed into the stomach. Barrett's esophagus was identified or suspected in eight cases (44%) by one observer and three (16%) by the second (P = 0.14). Although the Z-line was seen in the 18 cases that were qualified by both observers, there was an agreement in only six cases as to whether it was regular or irregular. Erosive gastroesophageal reflux disease (GERD) was scored as present in three and absent in six patients by both readers. Nonexisting feline esophagus, varices, and distal esophageal stricture were suspected in one patient each. CONCLUSIONS: Esophageal capsule endoscopy had a high interobserver variability and a low yield for short-segment Barrett's esophagus. Esophageal capsule endoscopy cannot be recommended for screening for short-segment Barrett's esophagus. (Am J Gastroenterol 2008;103:533-537). C1 [Qureshi, Waqar A.; Abudayyeh, Suhaib; Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Qureshi, Waqar A.; Abudayyeh, Suhaib; Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Wu, Justin] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [DeMarco, Daniel] Baylor Univ, Med Ctr, Dallas, TX USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. RI Wu, Justin/N-6916-2015 NR 26 TC 6 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2008 VL 103 IS 3 BP 533 EP 537 DI 10.1111/j.1572-0241.2007.01650.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 274DK UT WOS:000253981800006 PM 18047544 ER PT J AU Evans, J Palmer, B Eyler, L Kaschow, J AF Evans, Jovier Palmer, Barton Eyler, Lisa Kaschow, John TI LATE LIFE SCHIZOPHRENIA RESEARCH: CLINICAL, ETHICAL, AND TRANSLATIONAL APPROACHES SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Evans, Jovier] NIMH, NIH, Bethesda, MD 20892 USA. [Palmer, Barton; Eyler, Lisa] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kaschow, John] Western Psychiat Inst & Clin, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A15 EP A15 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800011 ER PT J AU Faison, W Martinez, M Nathaniel, V McGahee, S Resendez, C AF Faison, Warachal Martinez, Moises Nathaniel, Vernon McGahee, Shunda Resendez, Cynthia TI HOW TO TEACH CULTURAL COMPETENCE IN GERIATRIC PSYCHIATRY: ADDRESSING UNMET PATIENT NEEDS SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Faison, Warachal] Med Univ S Carolina, N Charleston, SC USA. [Martinez, Moises] Columbia Univ, Harlem Hosp Ctr, Ft Lee, NJ USA. [Nathaniel, Vernon] Howard Univ, Washington, DC 20059 USA. [McGahee, Shunda] Massachusetts Gen Hosp, Somerville, MA USA. [Resendez, Cynthia] Family Serv Agcy San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A26 EP A26 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800038 ER PT J AU Kyomen, H Nelson, R Trinh, NH Whitfield, T Lebowitz, B AF Kyomen, Helen Nelson, Randy Trinh, Nhi-Ha Whitfield, Theodore Lebowitz, Barry TI UNDERSTANDING AND MANAGING AGGRESSIVE BEHAVIORS IN GEROPSYCHIATRIC PATIENTS SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Kyomen, Helen] McLean Hosp, Belmont, MA 02178 USA. [Nelson, Randy] Ohio State Univ, Columbus, OH 43210 USA. [Trinh, Nhi-Ha; Whitfield, Theodore] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lebowitz, Barry] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A14 EP A14 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800009 ER PT J AU Kyomen, HH Whitfield, TH AF Kyomen, Helen H. Whitfield, Theodore H. TI Neuropsychiatric Conditions Associated with Aggression in Geropsychiatric Inpatients: Potential Targets for Intervention SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Kyomen, Helen H.] McLean Hosp, Belmont, MA 02178 USA. [Whitfield, Theodore H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A103 EP A103 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800166 ER PT J AU Lebowitz, B Sultzer, D Grossberg, G Segal-Gidan, F AF Lebowitz, Barry Sultzer, David Grossberg, George Segal-Gidan, Freddi TI CLINICAL RESEARCHERS DEBATE: THE COMPREHENSIVE TREATMENT OF ALZHEIMER'S DISEASE SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Lebowitz, Barry] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sultzer, David] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Grossberg, George] St Louis Univ, Sch Med, St Louis, MO USA. [Segal-Gidan, Freddi] Univ So Calif, Keck Sch Med, Downey, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A25 EP A25 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800034 ER PT J AU Martinez, J Davidson, J Allgulander, C Pollack, M Hartford, J Robinson, M Russell, J Perahia, D Wohlreich, M Raskin, J AF Martinez, James Davidson, Jonathan Allgulander, Christer Pollack, Mark Hartford, James Robinson, Michael Russell, James Perahia, David Wohlreich, Madelaine Raskin, Joel TI Efficacy and Tolerability of Duloxetine in Elderly Patients with Generalized Anxiety Disorder SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Martinez, James; Robinson, Michael; Russell, James; Wohlreich, Madelaine; Raskin, Joel] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Davidson, Jonathan] Duke Univ, Durham, NC USA. [Allgulander, Christer] Karolinska Inst, Huddinge, Sweden. [Pollack, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hartford, James] Hartford Res Grp, Cincinnati, OH USA. [Perahia, David] Gordon Hosp, Westminister, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A89 EP A89 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800140 ER PT J AU Nyer, M Fellows, I Kasckow, J Lawrence, EC Golshan, S Solorzano, E Zisook, S AF Nyer, Maren Fellows, Ian Kasckow, John Lawrence, Edith C. Golshan, Shah Solorzano, Ellen Zisook, Sidney TI The Relationship of Marital Status and Clinical Characteristics in Middle-Aged and Older Patients with Schizophrenia and Depressive Symptoms SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Nyer, Maren; Lawrence, Edith C.] Univ Virginia, Charlottesville, VA USA. [Fellows, Ian; Golshan, Shah; Solorzano, Ellen; Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John] Western Psychiat Inst Clin, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A84 EP A85 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800132 ER PT J AU Spira, AP Ensrud, K Covinsky, K Yaffe, K AF Spira, Adam P. Ensrud, Kristine Covinsky, Kenneth Yaffe, Kristine TI Anxiety Symptoms And Functional Impairment In Very Old Community-Dwelling Women SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Spira, Adam P.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ensrud, Kristine; Covinsky, Kenneth] Minneapolis VAMC, Minneapolis, MN USA. [Ensrud, Kristine; Covinsky, Kenneth] Univ Minnesota, Minneapolis, MN USA. [Spira, Adam P.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A51 EP A51 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800068 ER PT J AU Woo, BKP Harwood, DG Mandelkern, MM Walston, A Melrose, RJ Campa, O Sultzer, DL AF Woo, Benjamin K. P. Harwood, Dylan G. Mandelkern, Mark M. Walston, Amy Melrose, Rebecca J. Campa, Olivia Sultzer, David L. TI Executive Deficits in Alzheimer's Disease: An FDG-PET Imaging Study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Woo, Benjamin K. P.; Mandelkern, Mark M.] Univ Calif Los Angeles, Bakersfield, CA USA. [Harwood, Dylan G.; Walston, Amy; Melrose, Rebecca J.; Campa, Olivia; Sultzer, David L.] Univ Calif Los Angeles, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2008 VL 16 IS 3 SU 1 BP A98 EP A99 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YV UT WOS:000207905800157 ER PT J AU Roehrl, MHA Dzik, WS AF Roehrl, Michael H. A. Dzik, W. Sunny TI Weisses Blut - Leukapheresis in acute leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material C1 [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Roehrl, MHA (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2008 VL 83 IS 3 BP 254 EP 255 DI 10.1002/ajh.21064 PG 2 WC Hematology SC Hematology GA 268DV UT WOS:000253559700020 PM 17914717 ER PT J AU Higgins, AW Alkuraya, FS Bosco, AE Brown, KK Bruns, GAP Donovan, DJ Eisenman, R Fan, Y Farra, CG Ferguson, HL Gusella, JF Harris, DJ Herrick, SR Kelly, C Kim, HG Kishikawa, S Korf, BR Kulkarni, S Lally, E Leach, NT Lemyre, E Lewis, J Ligon, AH Lu, WN Maas, RL MacDonald, ME Moore, SDP Peters, RE Quade, BJ Quintero-Rivera, F Saadi, I Shen, Y Shendure, J Williamson, RE Morton, CC AF Higgins, Anne W. Alkuraya, Fowzan S. Bosco, Amy E. Brown, Kerry K. Bruns, Gail A. P. Donovan, Diana J. Eisenman, Robert Fan, Yanli Farra, Chantal G. Ferguson, Heather L. Gusella, James F. Harris, David J. Herrick, Steven R. Kelly, Chantal Kim, Hyung-Goo Kishikawa, Shotaro Korf, Bruce R. Kulkarni, Shashikant Lally, Eric Leach, Natalia T. Lemyre, Emma Lewis, Janine Ligon, Azra H. Lu, Weining Maas, Richard L. MacDonald, Marcy E. Moore, Steven D. P. Peters, Roxanna E. Quade, Bradley J. Quintero-Rivera, Fabiola Saadi, Irfan Shen, Yiping Shendure, Jay Williamson, Robin E. Morton, Cynthia C. TI Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTIPLE CONGENITAL-ANOMALIES; ZIMMERMANN-LABAND-SYNDROME; MENTAL-RETARDATION; CLEFT-LIP; TRANSLOCATION; DISRUPTION; REPAIR; GENE; DNA; HAPLOINSUFFICIENCY AB Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes, Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation. C1 [Higgins, Anne W.; Donovan, Diana J.; Farra, Chantal G.; Lally, Eric; Ligon, Azra H.; Peters, Roxanna E.; Quade, Bradley J.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Brown, Kerry K.; Gusella, James F.; Herrick, Steven R.; Shendure, Jay; Williamson, Robin E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Alkuraya, Fowzan S.; Fan, Yanli; Maas, Richard L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bosco, Amy E.; Ferguson, Heather L.; Kelly, Chantal; Leach, Natalia T.; Moore, Steven D. P.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Bruns, Gail A. P.; Eisenman, Robert] Childrens Hosp Boston, Dept Pediat, Div Genet, Boston, MA 02115 USA. [Gusella, James F.; Kim, Hyung-Goo; Kishikawa, Shotaro; Lewis, Janine; MacDonald, Marcy E.; Quintero-Rivera, Fabiola; Shen, Yiping] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Gusella, James F.; Kim, Hyung-Goo; Kishikawa, Shotaro; Lewis, Janine; MacDonald, Marcy E.; Quintero-Rivera, Fabiola; Shen, Yiping] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Korf, Bruce R.] Univ Alabama, Dept Genet, Birmingham, AL 35294 USA. [Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol, Div Lab & Genom Med, St Louis, MO 63110 USA. [Lemyre, Emma] Univ Montreal, Hop St Justine, Div Med Genet, Montreal, PQ H3T 1C5, Canada. [Lu, Weining] Boston Univ, Med Ctr, Dept Med, Renal Sect, Boston, MA 02118 USA. [MacDonald, Marcy E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM cmorton@partners.org RI Donovan, Diana/A-1256-2010; Alkuraya, Fowzan/A-1542-2009; OI Saadi, Irfan/0000-0002-6250-6651; Alkuraya, Fowzan/0000-0003-4158-341X; Shendure, Jay/0000-0002-1516-1865; Lu, Weining/0000-0002-6570-3044 FU NCI NIH HHS [P30CA06516, P30 CA006516]; NICHD NIH HHS [F32 HD043627]; NIDCD NIH HHS [F31 DC005712, F31 DC007540]; NIGMS NIH HHS [P01 GM061354, T32 GM007748] NR 36 TC 56 Z9 56 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 2008 VL 82 IS 3 BP 712 EP 722 DI 10.1016/j.ajhg.2008.01.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 275JN UT WOS:000254067800015 PM 18319076 ER PT J AU Lemaitre, RN Heckbert, SR Sotoodehnia, N Bis, JC Smith, NL Marciante, KD Hindorff, LA Lange, LA Lumley, TS Rice, KM Wiggins, KL Psaty, BM AF Lemaitre, Rozenn N. Heckbert, Susan R. Sotoodehnia, Nona Bis, Joshua C. Smith, Nicholas L. Marciante, Kristin D. Hindorff, Lucia A. Lange, Leslie A. Lumley, Thomas S. Rice, Kenneth M. Wiggins, Kerri L. Psaty, Bruce M. TI beta 1- and beta 2-adrenergic receptor gene beta-blocker use and risk of myocardial infarction and stroke SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID ESSENTIAL-HYPERTENSION; POLYMORPHISMS; METAANALYSIS; THERAPIES; HEALTH; METOPROLOL; AGENTS; HEART AB BACKGROUND The benefits of beta-blocker therapy may depend on underlying genetic susceptibility. METHODS We investigated the interaction of common variation in beta 1 and beta 2 adrenergic receptor (AR) genes with beta-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case-control study. Participants were treated pharmacologically for hypertension, aged 30-79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. RESULTS We observed an interaction of beta-blocker use with beta 1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other anti hypertensive medications, beta-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66,95% confidence interval (Cl); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88,95% Cl: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. P-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24,95% Cl: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70,95% Cl: 0.51-0.94). P-blocker use did not interact with beta 2-AR gene variation on the risks of MI and ischemic stroke. CONCLUSIONS These results, which require replication, suggest genetic variants in the beta 1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease. C1 [Lemaitre, Rozenn N.; Sotoodehnia, Nona; Bis, Joshua C.; Marciante, Kristin D.; Hindorff, Lucia A.; Wiggins, Kerri L.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Lumley, Thomas S.; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Lemaitre, RN (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM rozenl@u.washington.edu RI Rice, Kenneth/A-4150-2013 OI Rice, Kenneth/0000-0001-5779-4495 FU NHLBI NIH HHS [HL74745, HL43201, HL60739, HL68639, HL68986, HL73410]; NIA NIH HHS [AG09556] NR 24 TC 19 Z9 21 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2008 VL 21 IS 3 BP 290 EP 296 DI 10.1038/ajh.2007.71 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 264XF UT WOS:000253323000014 PM 18219297 ER PT J AU Ulloa, EW Silberbogen, AK Brown, K AF Ulloa, Erin Winters Silberbogen, Amy K. Brown, Kirstin TI Preoperative Psychosocial Evaluation of Penile Prosthesis Candidates SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE erectile dysfunction; sexual dysfunction; male; penile prosthesis; preoperative care ID ERECTILE DYSFUNCTION; MECHANICAL RELIABILITY; SEX THERAPY; PSYCHOSEXUAL ADJUSTMENT; GLYCOSYLATED HEMOGLOBIN; PATIENT SATISFACTION; FOLLOW-UP; SURGERY; IMPLANTATION; IMPOTENCE AB Penile prosthesis surgery is a recommended treatment option for a subset of patients who present with erectile dysfunction (ED). Although treatment outcome research indicates that patients are generally satisfied with this intervention, it remains an invasive procedure with risk for complications. A review of the literature reveals general agreement for the importance of a thorough preoperative evaluation to determine appropriateness for a penile implant; however, there are no known descriptions of such an evaluation in the literature. This article provides an introduction to the domains that are most relevant to assess in a patient who is considering penile implant surgery: sexual history (including organic and psychogenic causes of ED), success and utilization of other treatment interventions, relationship functioning, and patient expectations for and knowledge of the procedure. The advantages to this approach are presented, particularly in enhancing patient satisfaction with treatment outcomes. C1 [Ulloa, Erin Winters] VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. [Ulloa, Erin Winters; Silberbogen, Amy K.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Ulloa, EW (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM erin.ulloa2@va.gov FU NIDDK NIH HHS [5 R03 DK 71778-02] NR 52 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 J9 AM J MENS HEALTH JI Am. J. Mens Health PD MAR PY 2008 VL 2 IS 1 BP 68 EP 75 DI 10.1177/1557988307313439 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386FN UT WOS:000261867800008 PM 19477771 ER PT J AU Henson, JW Ulmer, S Harris, GJ AF Henson, J. W. Ulmer, S. Harris, G. J. TI Brain tumor imaging in clinical trials SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID HIGH-GRADE GLIOMAS; PHASE-II; RESPONSE CRITERIA; MALIGNANT GLIOMA; VOLUME; CHEMOTHERAPY; GLIOBLASTOMA; SURVIVAL AB There are substantial challenges in the radiologic evaluation of tumor size during clinical trials, and it is important for neuroradiologists to have a firm understanding of these issues. This review will examine measurement approaches, response criteria, selection of lesions for measurement, technical imaging considerations, interval between tumor measurements and response confirmation, and validity of imaging as a measure of efficacy. C1 [Henson, J. W.; Ulmer, S.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Brain Tumor Imaging, Boston, MA 02114 USA. [Henson, J. W.] Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. [Henson, J. W.; Harris, G. J.] Massachusetts Gen Hosp, Imaging Serv 3D, Boston, MA 02114 USA. [Henson, J. W.; Harris, G. J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Henson, J. W.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Henson, J. W.; Harris, G. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Brain Tumor Imaging, 55 Fruit St,Yawkey Nine E, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 20 TC 89 Z9 90 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2008 VL 29 IS 3 BP 419 EP 424 DI 10.3174/ajnr.A0963 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 275JC UT WOS:000254066700003 PM 18272557 ER PT J AU Gerten, KA Richter, HE Wheeler, TL Pair, LS Burgio, KL Redden, DT Varner, RE Hibner, M AF Gerten, Kimberly A. Richter, Holly E. Wheeler, Thomas L., II Pair, Lisa S. Burgio, Kathryn L. Redden, David T. Varner, R. Edward Hibner, Michael TI Intraabdominal pressure changes associated with lifting: implications for postoperative activity restrictions SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE intraabdominal pressure; pelvic floor disorders; postoperative instructions; weight lifting ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; FLOOR DISORDERS; RISK-FACTORS; OLDER WOMEN; PREVALENCE AB OBJECTIVE: The purpose of this study was to describe the effect of the lifting maneuver and the quantity of weight lifted on the generation of intraabdominal pressure. STUDY DESIGN: Forty-one women who underwent urodynamic evaluation performed 4 lifting maneuvers, each while lifting 0, 2.5, 5, 10, and 15 kg. The lifting maneuvers were routine activities that included squatting with and without assistance, lifting from a counter, and receiving weight. Pressure was recorded with a rectal microtip catheter. Each lift was performed twice, and the average pressure change was analyzed. RESULTS: When controlled for potential confounding variables, repeated-measures analysis of variance revealed a significant interaction between lift weight and lift maneuver (P = .001). Squatting was associated with generation of higher intraabdominal pressure than lifting from a counter or receiving weights into outstretched arms (P = .001). Lifting >= 2.5 kg resulted in significant changes in intraabdominal pressure, regardless of lift maneuver ( P < .001). CONCLUSION: Both the lifting maneuver and the quantity of weight should be considered when counseling patients regarding postoperative lifting. C1 [Gerten, Kimberly A.; Richter, Holly E.; Wheeler, Thomas L., II; Pair, Lisa S.; Varner, R. Edward] Univ Alabama, Sch Med, Dept Obstet & Gynecol, Div Womens Pelv Med & Reconstruct Surg, Birmingham, AL USA. [Burgio, Kathryn L.] Univ Alabama, Sch Med, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Redden, David T.] Univ Alabama, Sch Med, Dept Biostat, Birmingham, AL USA. [Burgio, Kathryn L.; Redden, David T.] Birmingham VA Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Hibner, Michael] St Josephs Hosp, Dept Obstet & Gynecol, Div Gynecol Surg, Phoenix, AZ USA. RP Gerten, KA (reprint author), 618 20th St S NHB 219, Birmingham, AL 35233 USA. EM gerten@uab.edu NR 22 TC 0 Z9 0 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2008 VL 198 IS 3 AR 306.e1 DI 10.1016/j.ajog.2007.09.004 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 270OL UT WOS:000253730000025 ER PT J AU Holland, GN AF Holland, Gary N. TI AIDS and ophthalmology: The first quarter century SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE RECOVERY UVEITIS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; CYTOMEGALOVIRUS CMV RETINITIS; OCULAR COMPLICATIONS; MAINTENANCE THERAPY; DEFICIENCY-SYNDROME; ERA; VIRUS AB PURPOSE: To describe changes in the acquired immunodeficiency syndrome (AIDS) epidemic that are important to ophthalmologists, to provide an overview of issues relevant to current evaluation and treatment of human immunodeficiency virus (HIV)-related eye disease, and to identify problems related to the eye and vision that require continued study. DESIGN: Literature review and commentary. METHODS: Selected articles from the medical literature and the author's clinical and research experiences over 25 years were reviewed critically. RESULTS: The AIDS epidemic has had a profound impact on ophthalmology since the ophthalmic manifestations of AIDS were first described in 1982. The introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of cytomegalovirus (CMV) retinitis, but has not eliminated, new cases altogether. Treatment strategies for CMV retinitis have evolved over the past decade. Current issues of importance include choice of initial anti,CMV drugs; time at which anti-CMV drug treatment is discontinued in patients who achieve immune recovery; strategies for monitoring patients at risk for disease reactivation; and management of complications (retinal detachment, immune recovery uveitis). Attention also is being directed to the problem of visual disturbances (reduced contrast sensitivity, altered color vision, visual field abnormalities) that can occur in HIV,infected individuals without infectious retinopathies. CONCLUSIONS: Ocular disorders associated with HIV disease remain important problems in the United States, despite. HAART, and increasingly are important worldwide. The approach to management of CMV retinitis has evolved from short-term treatment of a preterminal infection to the long-term management of what has become a chronic disease. Many challenges remain to be addressed. C1 [Holland, Gary N.] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Dept Ophthalmol,Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA. [Holland, Gary N.] Greater Los Angeles Vet Affairs Healthcare Serv, Los Angeles, CA USA. RP Holland, GN (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Dept Ophthalmol,Ocular Inflammatory Dis Ctr, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM uveitis@jsei.ucla.edu FU NEI NIH HHS [EY08057] NR 58 TC 54 Z9 63 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2008 VL 145 IS 3 BP 397 EP 408 DI 10.1016/j.ajo.2007.12.001 PG 12 WC Ophthalmology SC Ophthalmology GA 272EE UT WOS:000253841900003 PM 18282490 ER PT J AU Sayegh, RR Ang, LPK Foster, CS Dohlman, CH AF Sayegh, Rony R. Ang, Leonard P. K. Foster, C. Stephen Dohlman, Claes H. TI The Boston keratoprosthesis in Stevens-Johnson syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PENETRATING KERATOPLASTY; RISK-FACTORS AB PURPOSE: To evaluate the use of the Boston keratoprosthesis (KPro) in patients with Stevens-Johnson syndrome (SJS). DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Sixteen eyes of 15 patients with SJS under, went KPro surgery at the Massachusetts Eye and Ear Infirmary from January 2000 through December 2005. The preoperative, operative, and postoperative findings were recorded. All patients underwent either the type I or type II Boston KPro surgery by one surgeon (C.H.D.). Retention of the prosthesis, best-corrected visual acuity, the need for surgical revision, and postoperative complications were recorded. The outcomes were compared with those of an earlier group of patients from the 1990s. RESULTS: The mean age of patients was 50 +/- 18 years (range, 23 to 74 years), and the mean duration of their disease was 10 +/- 6.6 years. The mean follow,up period was 3.6 +/- 1.5 years (range, 10.2 months to 5.6 years). Ten eyes underwent type II KPro surgery, whereas six eyes underwent type I KPro surgery. Twelve eyes (75%) achieved a visual acuity of 20/200 or better after surgery, with eight eyes (50%) achieving excellent vision. of 20/40 or better. Visual acuity was maintained at 20/200 or better over a mean period of 2.5 +/- 2.0 years. Preexisting glaucoma was found to be a significant risk factor for visual loss. There were no cases of KPro extrusion or endophthalmitis. CONCLUSIONS: KPro in SJS has improved, largely because of the introduction of vancomycin prophylaxis and better glaucoma treatment. It seems to be superior to standard penetrating keratoplasty, with or without allografted stem cell transplantation, as judged from the literature. However, the outcome of the KPro in SJS is still substantially less favorable than in nonautoimmune diseases. C1 [Sayegh, Rony R.; Ang, Leonard P. K.; Foster, C. Stephen; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Ang, Leonard P. K.] Singapore Natl Eye Ctr, Singapore, Singapore. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 NR 16 TC 78 Z9 81 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2008 VL 145 IS 3 BP 438 EP 444 DI 10.1016/j.ajo.2007.11.002 PG 7 WC Ophthalmology SC Ophthalmology GA 272EE UT WOS:000253841900009 PM 18207122 ER PT J AU Mehta, RP Deschler, DG AF Mehta, Ritvik P. Deschler, Daniel G. TI Intraoperative diagnosis of facial nerve schwannoma at parotidectomy SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID NEURILEMOMA; NEUROMAS; MASS AB Objective: Our objective was to provide a diagnostic algorithm for facial nerve schwannomas presenting as a parotid mass. Study design: The study is a case report and literature review. Methods: A clinical case of a patient with an asymptomatic parotid mass diagnosed as a facial nerve schwannoma intraoperatively is presented. The patient's presentation and the diagnostic algorithm and surgical rationale are discussed. A review of the literature on facial nerve schwannomas is presented. Conclusions: Intraparotid facial nerve schwannomas are an extremely rare entity and are rarely diagnosed preoperatively. Most of these benign lesions can be managed conservatively with the goal of preserving facial nerve function. Intraoperatively, fine-needle aspiration and/or conservative biopsy in a nonstimulating portion of the lesion can be used to make the diagnosis. (c) 2008 Elsevier Inc. All rights reserved. C1 [Mehta, Ritvik P.; Deschler, Daniel G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM Danie_deschler@meei.harvard.edu NR 12 TC 10 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAR-APR PY 2008 VL 29 IS 2 BP 126 EP 129 DI 10.1016/j.amjoto.2007.03.001 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 274SU UT WOS:000254022100010 PM 18314025 ER PT J AU Mumy, KL Chen, XH Kelly, CP McCormick, BA AF Mumy, Karen L. Chen, Xinhua Kelly, Ciaran P. McCormick, Beth A. TI Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE probiotic; inflammation; neutrophil; barrier function ID NF-KAPPA-B; INTESTINAL EPITHELIAL MONOLAYERS; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; BACTERIAL DISSEMINATION; NEUTROPHIL MIGRATION; IMMUNE-RESPONSES; GNOTOBIOTIC MICE; BARRIER FUNCTION; XENOGRAFT MODEL AB Saccharomyces boulardii is gaining in popularity as a treatment for a variety of diarrheal diseases as well as inflammatory bowel disease. This study was designed to examine the effect of this yeast on infection by Shigella flexneri, a highly infectious and human host-adapted enteric pathogen. We investigated key interactions between the bacteria and host cells in the presence of the yeast in addition to a number of host responses including proinflammatory events and markers. Although the presence of the yeast during infection did not alter the number of bacteria that was able to attach or invade human colon cancer-derived T-84 cells, it did positively impact the tight junction protein zonula occluden-2 and significantly increase the barrier integrity of model epithelia. The yeast also decreased ERK, JNK, and NF-kappa B activation in response to S. flexneri, events likely responsible for the observed reductions in IL-8 secretion and the transepithelial migration of polymorphonuclear leukocytes across T-84 monolayers. These results, suggesting that the yeast allowed for a dampened inflammatory response, were confirmed in vivo utilizing a highly relevant model of human fetal colonic tissue transplanted into scid mice. Furthermore, a cell-free S. boulardii culture supernatant was also capable of reducing IL-8 secretion by infected T-84 cells. These data suggest that although the use of S. boulardii during infection with S. flexneri may alleviate symptoms associated with the inflammatory response of the host, it would not prevent infection. C1 [Mumy, Karen L.; Chen, Xinhua; McCormick, Beth A.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. [Mumy, Karen L.; McCormick, Beth A.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Chen, Xinhua; Kelly, Ciaran P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, 114 16th St,Rm 3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-33506, P01 DK033506, P30 DK040561, P30 DK040561-12] NR 53 TC 24 Z9 25 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2008 VL 294 IS 3 BP G599 EP G609 DI 10.1152/ajpgi.00391.2007 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 274HK UT WOS:000253992200002 PM 18032477 ER PT J AU Kang, L Sanders, NM Dunn-Meynell, AA Gaspers, LD Routh, VH Thomas, AP Levin, BE AF Kang, Ling Sanders, Nicole M. Dunn-Meynell, Ambrose A. Gaspers, Larry D. Routh, Vanessa H. Thomas, Andrew P. Levin, Barry E. TI Prior hypoglycemia enhances glucose responsiveness in some ventromedial hypothalamic glucosensing neurons SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE glucokinase; counterregulatory response; hypoglycemia-associated autonomic failure; calcium imaging; arcuate nucleus; ventromedial nucleus; ventromedial hypothalamus ID COUNTERREGULATORY HORMONE RESPONSES; SENSITIVE K+ CHANNELS; ACTIVATED PROTEIN-KINASE; ARCUATE NUCLEUS; RECURRENT HYPOGLYCEMIA; EXTRACELLULAR GLUCOSE; ENERGY HOMEOSTASIS; INHIBITED NEURONS; NEUROPEPTIDE-Y; FOOD-INTAKE AB Antecedent insulin-induced hypoglycemia (IIH) reduces adrenomedullary responses (AMR) to subsequent bouts of hypoglycemia. The ventromedial hypothalamus [VMH: arcuate (ARC) + ventromedial nuclei] contains glucosensing neurons, which are thought to be mediators of these AMR. Since type 1 diabetes mellitus often begins in childhood, we used juvenile (4- to 5-wk-old) rats to demonstrate that a single bout of IIH (5 U/kg sc) reduced plasma glucose by 24% and peak epinephrine by 59% 1 day later. This dampened AMR was associated with 46% higher mRNA for VMH glucokinase, a key mediator of neuronal glucosensing. Compared with neurons from saline-injected rats, ventromedial nucleus glucose-excited neurons from insulin-injected rats demonstrated a leftward shift in their glucose responsiveness (EC50 = 0.45 and 0.10 mmol/l for saline and insulin, respectively, P = 0.05) and a 31% higher maximal activation by glucose (P = 0.05), although this maximum occurred at a higher glucose concentration (saline, 0.7 vs. insulin, 1.5 mmol/l). Although EC50 values did not differ, ARC glucose-excited neurons had 19% higher maximal activation, which occurred at a lower glucose concentration in insulin-than saline-injected rats (saline, 2.5 vs. insulin, 1.5 mmol/l). In addition, ARC glucose-inhibited neurons from insulin-injected rats were maximally inhibited at a fivefold lower glucose concentration (saline, 2.5 vs. insulin, 0.5 mmol/l), although this inhibition declined at > 0.5 mmol/l glucose. These data suggest that the increased VMH glucokinase after IIH may contribute to the increased responsiveness of VMH glucosensing neurons to glucose and the associated blunting of the AMR. C1 [Kang, Ling; Dunn-Meynell, Ambrose A.; Levin, Barry E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Gaspers, Larry D.; Routh, Vanessa H.; Thomas, Andrew P.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ 07103 USA. [Dunn-Meynell, Ambrose A.; Levin, Barry E.] Vet Affairs Med Ctr, Neurol Serv, E Orange, NJ 07018 USA. [Sanders, Nicole M.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Sanders, Nicole M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Levin, BE (reprint author), VA Med Ctr, Neurol Serv 127C, 385 Tremont Ave, E Orange, NJ 07018 USA. EM levin@umdnj.edu RI Thomas, Andrew/C-6755-2013 FU NIDDK NIH HHS [DK-38422, DK-53182, DK-55619, DK-64566] NR 60 TC 21 Z9 22 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2008 VL 294 IS 3 BP R784 EP R792 DI 10.1152/ajpregu.00645.2007 PG 9 WC Physiology SC Physiology GA 271HE UT WOS:000253778700013 PM 18094065 ER PT J AU Mahon, MJ AF Mahon, Matthew J. TI Ezrin promotes functional expression and parathyroid hormone-mediated regulation of the sodium-phosphate cotransporter 2a in LLC-PK1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proximal tubule; hormonal regulation ID OPOSSUM KIDNEY-CELLS; TRANSMEMBRANE CONDUCTANCE REGULATOR; PROTEIN-COUPLED RECEPTOR; I COTRANSPORTERS; PLASMA-MEMBRANE; OK CELLS; INTRACELLULAR CALCIUM; ACTIN CYTOSKELETON; PHOSPHOLIPASE-C; DOWN-REGULATION AB The sodium-phosphate cotransporter 2a (NPT2a) is the principal phosphate transporter expressed in the brush border of renal proximal tubules and is downregulated by parathyroid hormone (PTH) through an endocytic mechanism. Apical membrane expression of NPT2a is dependent on interactions with the sodium-hydrogen exchanger regulatory factor 1 (NHERF-1). An LLC-PK1 renal cell line stably expressing the PTH receptor (PTH1R) and NHERF-1, termed B28-N1, fails to functionally express NPT2a. In B28-N1 cells, NHERF-1 and NPT2a are inappropriately localized to the cytoplasm. Ezrin, in the activated state, is capable at linking NHERF-1-assembled complexes to the actin cytoskeleton. Early-passage LLC-PK1 cells stably transfected with either empty vector or wild-type ezrin express a comparable level of the active, T567 phosphorylated form of ezrin and are capable of functionally expressing NPT2a. Colocalization of the PTH1R, NPT2a, and ezrin exists and is prominently associated with actin-containing microvilli in apical domains of these cells. Upon PTH treatment, the PTH1R, NPT2a, NHERF-1, and ezrin colocalize to endocytic vesicles and NPT2a-dependent phosphate uptake is markedly inhibited. LLC-PK1 cells expressing the constitutively active ezrin (T567D) display enhanced NPT2a functional expression and PTH-mediated regulation of phosphate. Expression of a dominant-negative ezrin, consisting of the NH(2)-terminal half of the protein, markedly disrupts NPT2a-dependent phosphate uptake. PTH does not appear to alter ezrin phosphorylation at T567. Instead, PTH perhaps initiates NPT2a endocytosis by inducing reorganization of the actin-containing microvilli in a process that is blocked by the actin-stabilizing compound jasplakinolide. C1 [Mahon, Matthew J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Mahon, Matthew J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Mahon, MJ (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. EM mahon@helix.mgh.harvard.edu FU NIDDK NIH HHS [P01-DK-11794] NR 47 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2008 VL 294 IS 3 BP F667 EP F675 DI 10.1152/ajprenal.00276.2007 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 268IW UT WOS:000253574500025 PM 18184743 ER PT J AU Wilhelm, S Buhlmann, U Tolin, DF Meunier, SA Pearlson, GD Reese, HE Cannistraro, P Jenike, MA Rauch, SL AF Wilhelm, Sabine Buhlmann, Ulrike Tolin, David F. Meunier, Suzanne A. Pearlson, Godfrey D. Reese, Hannah E. Cannistraro, Paul Jenike, Michael A. Rauch, Scott L. TI Augmentation of behavior therapy with D-cycloserine for obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th World Congress of Behavioural and Cognitive Therapies CY JUL 11-14, 2007 CL Barcelona, SPAIN ID ANTAGONIST MK-801 BLOCKS; PLACEBO-CONTROLLED TRIAL; LONG-TERM POTENTIATION; EXPOSURE THERAPY; CONDITIONED FEAR; CLINICAL IMPLICATIONS; RESPONSE PREVENTION; EXTINCTION; AMYGDALA; SCHIZOPHRENIA AB Objective: This study examined whether D-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). Method: A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/ treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. Results: Relative to the placebo group, the D-cycloserine group's OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine group's depressive symptoms were significantly more improved at posttreatment. Conclusions: These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of longterm potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist. C1 Massachusetts Gen Hosp, Obsess Compuls Disorders Clin, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, McLean Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Inst Living, Hartford, CT USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Obsess Compuls Disorders Clin, Dept Psychiat, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 33 TC 199 Z9 201 U1 4 U2 18 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2008 VL 165 IS 3 BP 335 EP 341 DI 10.1176/appi.ajp.2007.07050776 PG 7 WC Psychiatry SC Psychiatry GA 271HL UT WOS:000253779400013 PM 18245177 ER PT J AU Fava, M Rush, AJ Alpert, JE Balasubramani, GK Wisniewski, SR Carmin, CN Biggs, MM Zisook, S Leuchter, A Howland, R Warden, D Trivedi, MH AF Fava, Maurizio Rush, A. John Alpert, Jonathan E. Balasubramani, G. K. Wisniewski, Stephen R. Carmin, Cheryl N. Biggs, Melanie M. Zisook, Sidney Leuchter, Andrew Howland, Robert Warden, Diane Trivedi, Madhukar H. TI Difference in treatment outcome in outpatients with anxious versus nonanxious depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; ILLNESS RATING-SCALE; REPORT QIDS-SR; MAJOR DEPRESSION; RELIEVE DEPRESSION; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; ANXIETY; SYMPTOMATOLOGY AB Objective: About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. Method: A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/ somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression. Results: In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options. Conclusions: Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. San Diego VA Med Ctr, San Diego, CA USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM mfava@partners.org RI Biggs, Dr. Melanie/C-1468-2010; Carmin, Cheryl/F-8004-2014; Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [R01 MH080015, N01 MH 90003, R01 MH080015-01] NR 44 TC 326 Z9 340 U1 3 U2 25 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2008 VL 165 IS 3 BP 342 EP 351 DI 10.1176/appi.ajp.2007.06111868 PG 10 WC Psychiatry SC Psychiatry GA 271HL UT WOS:000253779400014 PM 18172020 ER PT J AU Chae, DH Takeuchi, DT Barbeau, EM Bennett, GG Lindsey, J Krieger, N AF Chae, David H. Takeuchi, David T. Barbeau, Elizabeth M. Bennett, Gary G. Lindsey, Jane Krieger, Nancy TI Unfair treatment, racial/ethnic discrimination, ethnic identification, and smoking among Asian Americans in the National Latino and Asian American study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PERCEIVED RACIAL-DISCRIMINATION; AFRICAN-AMERICANS; MENTAL-HEALTH; TOBACCO USE; PSYCHIATRIC EPIDEMIOLOGY; PACIFIC-ISLANDERS; BLOOD-PRESSURE; YOUNG-ADULTS; SELF-ESTEEM; IDENTITY AB Objectives. We examined the relations of self-report of general unfair treatment and self-report of race/ethnicity-specific discrimination with current smoking among Asian Americans. We investigated whether ethnic identification moderated either association. Methods. Weighted logistic regressions were performed among 1977 Asian Americans recruited to the National Latino and Asian American Study (2002-2003). Results. In weighted multivariate logistic regression models including both general unfair treatment and racial/ethnic discrimination, odds of current smoking were higher among Asian Americans who reported high levels of unfair treatment (odds ratio [OR] = 2.80; 95% confidence interval [01 = 1.13, 6.95) and high levels of racial/ethnic discrimination (OR=2.40; 95% CI=0.94, 6.12) compared with those who reported no unfair treatment and discrimination, respectively. High levels of ethnic identification moderated racial/ethnic discrimination (F-3 = 3.25; P= .03). High levels of ethnic identification were associated with lower probability of current smoking among participants reporting high levels of racial/ethnic discrimination. Conclusions. Our findings suggest that experiences of unfair treatment and racial/ethnic discrimination are risk factors for smoking among Asian Americans. Efforts to promote ethnic identification may be effective in mitigating the influence of racial/ethnic discrimination on smoking in this population. C1 [Chae, David H.; Barbeau, Elizabeth M.; Bennett, Gary G.; Krieger, Nancy] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Chae, David H.; Takeuchi, David T.] Univ Washington, Sch Social Work, Seattle, WA 98105 USA. [Barbeau, Elizabeth M.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Lindsey, Jane] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Chae, DH (reprint author), Univ Washington, Sch Social Work, Box 354900,4101 15th Ave NE, Seattle, WA 98105 USA. EM dhchae@post.harvard.edu; dt5@u.washington.edu RI Chae, David/F-6956-2015 FU NICHD NIH HHS [R24 HD042828-10, R24 HD042828]; NIMH NIH HHS [P01 MH059876, P01-MH059876, U01 MH062207, U01 MH062209, U01-MH062207, U01-MH062209] NR 64 TC 85 Z9 85 U1 4 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2008 VL 98 IS 3 BP 485 EP 492 DI 10.2105/AJPH.2006.102012 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270TG UT WOS:000253742500020 PM 18235073 ER PT J AU Ackerson, LK Kawachi, I Barbeau, EM Subramanian, SV AF Ackerson, Leland K. Kawachi, Ichiro Barbeau, Elizabeth M. Subramanian, S. V. TI Effects of individual and proximate educational context on intimate partner violence: A population-based study of women in India SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RURAL SOUTH-INDIA; DOMESTIC VIOLENCE; MARITAL VIOLENCE; NORTHERN INDIA; HEALTH; MULTILEVEL; ASSOCIATIONS; PREVALENCE; BEHAVIOR; STATES AB Objectives. We examined the role of women's education and proximate educational context on intimate partner violence (IPV). Methods. We examined a sample of 83 627 married women aged 15 to 49 years from the 1998 to 1999 Indian National Family Health Survey. We used multilevel multiple logistic regression modeling to estimate the relative effect of women's and their husband's levels of education, spousal education differential, and community-level literacy on women's risk of recent and lifetime IPV. Results. In adjusted models, odds of recent IPV among women without any education were 5.61 times (95% confidence interval [CI] = 3.53, 8.92) those of college-educated women, and odds among wives of uneducated men were 1.84 times (95% CI = 1.44, 2.35) those of wives of college-educated men. Women with more education than their husbands were more likely than those with educational parity to report recent IPV (odds ratio [OR] = 1.18; 95% CI = 1.05, 1.33). The results were similar for lifetime IPV. After we controlled for individual factors, as community male and female literacy levels increased, likelihood of IPV declined. Conclusions. Although increasing women's levels of education is crucial to reducing IPV for women, proximate educational context is also an important factor in reducing this public health burden. C1 [Ackerson, Leland K.; Kawachi, Ichiro; Barbeau, Elizabeth M.; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Barbeau, Elizabeth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Subramanian, SV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge Bldg,7th Flr, Boston, MA 02115 USA. EM svsuhram@hsph.harvard.edu FU NHLBI NIH HHS [1-K25-HL081275, K25 HL081275] NR 54 TC 66 Z9 66 U1 4 U2 18 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2008 VL 98 IS 3 BP 507 EP 514 DI 10.2105/AJPH.2007.113738 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270TG UT WOS:000253742500023 PM 18235066 ER PT J AU Slatore, CG Littman, AJ Au, DH Satia, JA White, E AF Slatore, Christopher G. Littman, Alyson J. Au, David H. Satia, Jessie A. White, Emily TI Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE bronchial neoplasm; diet; dietary supplements; public health ID FOOD FREQUENCY QUESTIONNAIRE; THE-SCIENCE CONFERENCE; BETA-CAROTENE; WOMENS-HEALTH; VEGETABLE CONSUMPTION; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; CONTROLLED-TRIAL; POOLED ANALYSIS; UNITED-STATES AB Rationale: Lung cancer is the leading cause of cancer-related mortality in the United States. Although supplements are used by half the population, limited information is available about their specific effect on lung cancer risk. Objectives: To explore the association of supplemental multivitamins, vitamin C, vitamin E, and folate with incident lung cancer. Methods: Prospective cohort of 77,721 men and women aged 50-76 years from Washington State in the VITAL (VITamins And Lifestyle) study. Cases were identified through the Seattle-Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. Measurements and Main Results: Hazard ratios (HRs) for incident lung cancer according to 10-year average daily use of supplemental multivitamins, vitamin C, vitamin E, and folate. A total of 521 cases of lung cancer were identified. Adjusting for smoking, age, and sex, there was no inverse association with any supplement. Supplemental vitamin E was associated with a small increased risk of lung cancer (HR, 1.05 for every 100-mg/d increase in dose; 95% confidence interval [CI], 1.00-1.09; P = 0.033).This risk of supplemental vitamin E was largely confined to current smokers (HR, 1.11 for every 100-mg/d increase; 95% CI, 1.03-1.19; P < 0.01) and was greatest for non-small cell lung cancer (HR, 1.07 for every 1 00-mg/d increase; 95% CI, 1.02-1.12; P = 0.004). Conclusions- Supplemental multivitamins, vitamin C, vitamin E, and folate were not associated with a decreased risk of lung cancer. Supplemental vitamin E was associated with a small increased risk. Patients should be counseled against using these supplements to prevent lung cancer. C1 [Slatore, Christopher G.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Littman, Alyson J.; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Littman, Alyson J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Slatore, CG (reprint author), Univ Washington, Div Pulm & Crit Care Med, 1959 NE Pacific St,Box 356522, Seattle, WA 98195 USA. EM cslatore@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 FU NCI NIH HHS [CA74846] NR 56 TC 57 Z9 63 U1 2 U2 19 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2008 VL 177 IS 5 BP 524 EP 530 DI 10.1164/rccm.200709-1398OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268EH UT WOS:000253561000011 PM 17989343 ER PT J AU Torriani, M Thomas, BJ Bredella, MA Ouellette, H AF Torriani, Martin Thomas, Bijoy J. Bredella, Miriam A. Ouellette, Hugue TI MRI of metatarsal head subchondral fractures in patients with forefoot pain SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE foot; Freiberg's infraction; metatarsal; MRI; stress fracture ID FREIBERGS INFRACTION; STRESS-FRACTURES; DISEASE; VARIANT AB OBJECTIVE. The purpose of our study was to determine the MRI features of metatarsal head subchondral fractures in symptomatic adults. MATERIALS AND METHODS. A retrospective review of foot MRI procedures was performed to detect cases of metatarsal head subchondral fractures over a 6-year period. MR images of selected cases were analyzed by two reviewers for the presence of subchondral fracture, marrow edema-like pattern, metatarsal head flattening, and subchondral sclerosis. Patients with a history of foot surgery, infection, or inflammatory arthritis were excluded. Assessment for coexisting osseous and soft-tissue abnormalities was also performed. RESULTS. Subchondral fractures of the metatarsal heads were seen in 14 patients. All patients were women. The metatarsal head most commonly affected was the second (71%, 10/14) and the dorsal third of the metatarsal articular surface was involved in 79% (11/14). MRI findings of subchondral fracture of the metatarsal head with severe marrow edema-like pattern were seen in 71% (10/14), suggesting early stage changes. Metatarsal head collapse with subchondral sclerosis and mild or absent marrow edema-like pattern were seen in 29% (4/14) indicating late-stage changes. Concurrent abnormalities included three patients (21%) with metatarsal shaft fractures and one patient (7%) with an interdigital neuroma. One subject was treated surgically. CONCLUSION. Subchondral fractures of the-metatarsal heads can be detected on MR examinations of adults with forefoot pain. A subchondral fracture with associated marrow edema-like pattern is the most common presentation and likely reflects early stages of metatarsal head infraction. C1 [Torriani, Martin; Thomas, Bijoy J.; Bredella, Miriam A.; Ouellette, Hugue] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St, YAW 6E, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu NR 14 TC 12 Z9 12 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2008 VL 190 IS 3 BP 570 EP 575 DI 10.2214/AJR.07.2847 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266GD UT WOS:000253421600007 PM 18287423 ER PT J AU Stewart, BG Gervais, DA O'Neill, MJ Boland, GW Hahn, PF Mueller, PR AF Stewart, Bruce G. Gervais, Debra A. O'Neill, Mary J. Boland, Giles W. Hahn, Peter F. Mueller, Peter R. TI Imaging and percutaneous treatment of secondarily infected hepatic infarctions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abscess drainage; hepatic infarction; hepatic transplantation; polymicrobial infections; superinfection; Whipple procedure ID CT FINDINGS; LIVER-ABSCESS; ARTERIAL INSUFFICIENCY; DRAINAGE; TRANSPLANTATION; COMPLICATIONS; EXPERIENCE; SPECTRUM; DISEASE AB OBJECTIVE. The objective of our study was to describe the imaging features and success rate of percutaneously treated infected hepatic infarctions. MATERIALS AND METHODS. Three hundred ninety-two patients had percutaneous liver abscess aspiration and drainage or aspiration and intraoperative debridement at our institution between 1990 and 2003. One hundred fifty-one of these patients underwent CT at least 2 days before the drainage procedure and immediately before the procedure. Retrospective review of the imaging and medical records identified 13 patients with microbiologically documented liver abscesses who had liver lesions consistent with hepatic infarction on the baseline CT. RESULTS. Twenty-one hepatic infarctions in 13 patients were documented on baseline CT, 15 of which became secondarily infected. Ten of 15 patients with infected infarctions had undergone either hepatic transplantation or the Whipple procedure. Although the left lobe was slightly more commonly infarcted than the right lobe (54% vs 46%, respectively), right lobe infarctions were more commonly superinfected than left lobe infarctions (61% vs 39%); however, neither of these distinctions was statistically significant. Twelve of 13 patients underwent percutaneous drainage. The duration of catheter drainage was significantly longer in patients in whom catheter drainage was complicated by biliary communication than those without biliary communication (61 vs 19 days, respectively). Eleven of 12 patients (92%) responded to drainage such that they survived to discharge from the hospital. CONCLUSION. Patients with hepatic infarctions are at risk for secondary infection, particularly those patients having undergone surgery involving the porta hepatis. Percutaneous abscess drainage can be performed safely with excellent technical and clinical outcomes in this complex patient population. C1 [Stewart, Bruce G.; Gervais, Debra A.; O'Neill, Mary J.; Boland, Giles W.; Hahn, Peter F.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, White 270, Boston, MA 02114 USA. EM pmueller@partners.org NR 24 TC 7 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2008 VL 190 IS 3 BP 601 EP 607 DI 10.2214/AJR.07.2005 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266GD UT WOS:000253421600014 PM 18287428 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B AF Benacerraf, Beryl R. Shipp, Thomas D. Bromley, Bryann TI Which patients benefit from a 3D reconstructed coronal view of the uterus added to standard routine 2D pelvic sonography? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE 3D sonography; infertility; obstetrics and gynecology; pelvic sonography; women's imaging ID 3-DIMENSIONAL ULTRASOUND; GYNECOLOGY; ANOMALIES AB OBJECTIVE. The objective of our study was to evaluate whether a 3D reconstructed coronal view of the uterus provides added benefit to standard gynecologic sonography. MATERIALS AND METHODS. Sixty-six consecutive patients underwent standard 2D pelvic sonography followed by 3D sonography. The physician determined whether the reconstructed coronal view of the uterus was helpful to make a diagnosis not possible with the 2D scan, helpful to be more confident of a diagnosis suspected on the basis of the 2D scan, or not helpful. Comparison of the demographic information, sonographic findings, and endometrial thickness was made between the patient groups. RESULTS. The 3D coronal views of the uterus added value to the 2D scan in 16 (24%) of the 66 patients. In five of these 16 patients, the coronal view added information about findings not seen using 2D imaging. In the other 11 patients, the diagnostic findings were more confidently seen using the coronal view. The coronal view added no information in 50 patients. The coronal view was helpful in four (12.5%) of 32 patients with an endometrium < 5 mm, one of six patients whose endometrium was incompletely seen with 2D sonography, and 11 (39%) of 28 patients whose endometrium measured >= 5 mm. The coronal view did not provide benefit in patients who had normal findings on 2D scanning. In three patients referred because of infertility, uterine shape anomalies were diagnosed using the coronal view. CONCLUSION. The 3D coronal view of the uterus is a valuable adjunct to a 2D pelvic scan, particularly in patients presenting with infertility or suspected endometrial lesions. In addition, the coronal view is helpful in patients with an endometrium >= 5 mm. C1 [Benacerraf, Beryl R.] Diagnost Ultrasound Assoc, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Benacerraf, Beryl R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Benacerraf, Beryl R.; Shipp, Thomas D.; Bromley, Bryann] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Benacerraf, Beryl R.; Shipp, Thomas D.; Bromley, Bryann] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Assoc, 333 Longwood Ave, Boston, MA 02115 USA. NR 7 TC 13 Z9 13 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2008 VL 190 IS 3 BP 626 EP 629 DI 10.2214/AJR.07.2632 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266GD UT WOS:000253421600018 PM 18287431 ER PT J AU Singh, AK Hahn, PF Gervais, D Vijayraghavan, G Mueller, PR AF Singh, Ajay K. Hahn, Peter F. Gervais, Debra Vijayraghavan, Gopal Mueller, Peter R. TI Dropped appendicolith: CT findings and implications for management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abscess; appendectomy; dropped appendicolith ID LAPAROSCOPIC APPENDECTOMY; RETAINED FECALITH; ABSCESSES; REMOVAL AB OBJECTIVE. The aim of this study was to discern the CT features of appendicoliths retained after appendectomy and evaluate the management options. CONCLUSION. Retained, or dropped, appendicolith most often presents as an area of high attenuation less than I cm in diameter with an associated abscess close to the cecum or Morison's pouch. CT-guided drainage can be used to manage abscesses associated with dropped appendicolith in selected cases. C1 [Singh, Ajay K.; Vijayraghavan, Gopal] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Singh, Ajay K.; Hahn, Peter F.; Gervais, Debra; Mueller, Peter R.] Univ Massachusetts, Mem Med Ctr, Dept Radiol, Worcester, MA 01605 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 13 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2008 VL 190 IS 3 BP 707 EP 711 DI 10.2214/AJR.07.2917 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266GD UT WOS:000253421600032 PM 18287442 ER PT J AU Prabhakar, HB Rabinowitz, CB Gibbons, FK O'Donnell, WJ Shepard, JAO Aquino, SL AF Prabhakar, Hirna B. Rabinowitz, Chad B. Gibbons, Fiona K. O'Donnell, Walter J. Shepard, Jo-Anne O. Aquino, Suzanne L. TI Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; FDG PET; MOCT; PET/CT; sarcoidosis ID POSITRON-EMISSION-TOMOGRAPHY; LYMPHOMA; MANIFESTATIONS; SCINTIGRAPHY AB Objective The objectives of this article are to discuss the epidemiology and natural history of sarcoidosis; to review the classic imaging features of sarcoidosis on radiography, CT, and Ga-67 nuclear medicine scans; and to present clinical examples of sarcoidosis as seen on PET and PET/CT in the chest, abdomen and pelvis, and bones. Conclusion The imaging features of sarcoidosis are diverse and can be seen on a variety of imaging techniques. It is important for radiologists and nuclear medicine physicians to recognize the common imaging features and patterns of sarcoidosis in order to raise the possibility in the appropriate clinical setting. C1 [Prabhakar, Hirna B.; Rabinowitz, Chad B.; Shepard, Jo-Anne O.; Aquino, Suzanne L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gibbons, Fiona K.; O'Donnell, Walter J.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. RP Prabhakar, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM himaprab@gmail.com NR 16 TC 41 Z9 43 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2008 VL 190 IS 3 SU S BP S1 EP S6 DI 10.2214/AJR.07.7001 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266EP UT WOS:000253417600001 PM 18287458 ER PT J AU Li, G Papannagari, R Li, M Bingham, J Nha, KW Allred, D Gill, T AF Li, Guoan Papannagari, Ramprasad Li, Meng Bingham, Jeffrey Nha, Kyung W. Allred, Dain Gill, Thomas TI Effect of posterior cruciate ligament deficiency on in vivo translation and rotation of the knee during weightbearing flexion SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE posterior cruciate ligament (PCL); PCL injury; in vivo knee kinematics; PCL reconstruction ID SIMULATED MUSCLE LOADS; TERM-FOLLOW-UP; NATURAL-HISTORY; RECONSTRUCTED KNEE; JOINT KINEMATICS; SURGICAL REPAIR; SITU FORCES; ACUTE TEARS; INJURIES; GRAFT AB Background: The effect of posterior cruciate ligament (PCL) deficiency on 6 degrees of freedom in vivo knee-joint kinematics is unclear. Hypothesis: In addition to constraining anterior-posterior translation, the PCL also functions to constrain the medial-lateral translation and rotation of the knee during weightbearing flexion of the knee. Study Design: Controlled laboratory study. Methods: Eight patients with a PCL injury in 1 knee and the other intact were scanned with magnetic resonance imaging, and 3-dimensional models of the femur and tibia were created for both knees. Each knee was imaged during quasistatic weightbearing flexion (from 00 to 105 degrees) using a dual-orthogonal fluoroscopic system. The translation and rotation of the PCL-deficient knee were compared with the intact contralateral control. Results: Posterior cruciate ligament deficiency caused an increase in posterior tibial translation beyond 301 of flexion compared with the intact contralateral knees. At 901 of flexion, PCL deficiency increased posterior tibial translation by 3.5 mm (P < .05). In the medial-lateral direction, PCL deficiency resulted in a 1.1 mm increase in lateral tibial translation at 901 of flexion (P < .05). With regard to rotation, PCL deficiency caused a significantly lower varus rotation (on average, 0.6 degrees lower) at 90 degrees of flexion. Posterior cruciate ligament deficiency caused a decreased internal tibial rotation throughout the range of flexion, but no significant difference was detected. Conclusions: This study quantitatively describes the effect of PCL injury on 6 degrees of freedom kinematics of the knee during quasistatic weightbearing flexion. Using the intact contralateral side as a control, we found that PCL injuries not only affect anterior-posterior tibial translation but also medial-lateral translation and rotation of the knee. Clinical Relevance: These data provide baseline knowledge of the in vivo kinematics of the knee after PCL injury. Surgical reconstruction of the injured PCL, either using single-bundle or double-bundle technique, should not only focus on restoration of posterior stability of the knee but also the medial-lateral stability as well as the rotational stability. These findings may help to explain the long-term degenerative changes seen in PCL-deficient knees. C1 [Li, Guoan; Papannagari, Ramprasad; Li, Meng; Bingham, Jeffrey; Nha, Kyung W.; Allred, Dain; Gill, Thomas] Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Li, Guoan; Papannagari, Ramprasad; Li, Meng; Bingham, Jeffrey; Nha, Kyung W.; Allred, Dain; Gill, Thomas] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Li, Meng] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Bingham, Jeffrey] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Nha, Kyung W.] Inge Univ, Dept Orthopaed Surg, Ilsan, South Korea. [Nha, Kyung W.] Ilsanpaik Hosp, Ilsan, South Korea. RP Li, G (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org RI Bingham, Jeffrey/I-6901-2012 OI Bingham, Jeffrey/0000-0002-9590-8526 FU NIAMS NIH HHS [AR052408] NR 41 TC 36 Z9 46 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAR PY 2008 VL 36 IS 3 BP 474 EP 479 DI 10.1177/0363546507310075 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 265PS UT WOS:000253374000005 PM 18057390 ER PT J AU Reinold, MM Wilk, KE Macrina, LC Sheheane, C Dun, S Fleisig, GS Crenshaw, K Andrews, JR AF Reinold, Michael M. Wilk, Kevin E. Macrina, Leonard C. Sheheane, Chris Dun, Shouchen Fleisig, Glenn S. Crenshaw, Ken Andrews, James R. TI Changes in shoulder and elbow passive range of motion after pitching in professional baseball players SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE overhead throwing athlete; glenohumeral joint; capsule; internal impingement ID ROTATOR CUFF MUSCLES; ECCENTRIC EXERCISE; ELECTROMYOGRAPHIC ANALYSIS; GLENOHUMERAL JOINT; THROWING SHOULDER; PITCHERS; STIFFNESS; BIOMECHANICS; SORENESS; DAMAGE AB Background: The overhead throwing athlete has unique range of motion characteristics of the shoulder and elbow. Numerous theories exist to explain these characteristics; however, the precise cause is not known. Although it is accepted that range of motion is altered, the acute effect of baseball pitching on shoulder and elbow range of motion has not been established. Hypothesis: There will be a reduction in passive range of motion immediately after baseball pitching. Study Design: Controlled laboratory study. Methods: Sixty-seven asymptomatic male professional baseball pitchers participated in the study. Passive range of motion measurements were recorded using a customized bubble goniometer for shoulder external rotation, shoulder internal rotation, total shoulder rotational motion, elbow flexion, and elbow extension on the dominant and nondominant arms. Testing was performed on the first day of spring training. Measurements were taken before, immediately after, and 24 hours after pitching. Results: A significant decrease in shoulder internal rotation (-9.5 degrees), total motion (-10.7 degrees), and elbow extension (-3.2 degrees) occurred immediately after baseball pitching in the dominant shoulder (P < .001). These changes continued to exist 24 hours after pitching. No differences were noted on the nondominant side. Conclusion: Passive range of motion is significantly decreased immediately after baseball pitching. This decrease in range of motion continues to be present 24 hours after throwing. High levels of eccentric muscle activity have previously been observed in the shoulder external rotators and elbow flexors during pitching. These eccentric muscle contractions may contribute to acute musculotendinous adaptations and altered range of motion. The results of this study may suggest a newly defined mechanism to range of motion adaptations in the overhead throwing athlete resulting from acute musculoskeletal adaptations, in addition to potential osseous and capsular adaptations. C1 [Reinold, Michael M.] Boston Red Sox Basebell Club, Boston, MA USA. [Reinold, Michael M.] Massachusetts Gen Hosp, Dept Orthoped, Sports Med Div, Boston, MA 02114 USA. [Wilk, Kevin E.; Macrina, Leonard C.; Sheheane, Chris] Champ Sports Med, Birmingham, AL USA. [Wilk, Kevin E.; Dun, Shouchen; Fleisig, Glenn S.; Andrews, James R.] Amer Sports Med Inst, Birmingham, AL USA. [Crenshaw, Ken] Arizona Diamondbacks Baseball Club, Phoenix, AZ USA. [Andrews, James R.] Alabama Sports Med & Orthoped Ctr, Birmingham, AL USA. RP Reinold, MM (reprint author), MGH Sports Med Ctr, Fenway Pk 4,Yawkey Way, Boston, MA 02215 USA. EM mreinold@redsox.com NR 34 TC 66 Z9 66 U1 3 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAR PY 2008 VL 36 IS 3 BP 523 EP 527 DI 10.1177/0363546507308935 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 265PS UT WOS:000253374000012 PM 17991783 ER PT J AU Provenza, C Young, RH Prat, J AF Provenza, Claudia Young, Robert H. Prat, Jaime TI Anaplastic carcinoma in mucinous ovarian tumors - A clinicopathologic study of 34 cases emphasizing the crucial impact of stage on prognosis, their histologic spectrum, and overlap with sarcomalike mural nodules SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovarian mucinous tumor; anaplastic carcinoma; sarcomalike mural nodules; stage; prognosis ID CYSTADENOCARCINOMA AB Several types of mural nodules may develop in the wall of mucinous tumors of the ovary. The histopathologic features and prognosis of foci/nodules of anaplastic carcinoma are not well known. Although they were first thought to carry an invariably unfavorable prognosis, recent data indicate that this does not necessarily apply to stage la tumors. Slides from 34 consultation cases of mucinous ovarian tumors with foci/ nodules of anaplastic carcinoma were reviewed and classified on the basis of their morphologic features. Cytokeratin stains were done in selected cases. Staging, treatment, and follow-up information were obtained. The foci/nodules of anaplastic carcinoma were classified histologically into 3 groups: (a) rhabdoid (n = 12) having a diffuse arrangement of cells with large, bright, eosinophilic cytoplasms, eccentric nuclei, and one or more prominent nucleoli; (b) sarcomatoid (n = 10) characterized by a spindle cell proliferation, with atypical and vesicular nuclei often with herringbone pattern; and (c) pleomorphic (n 12) exhibiting overlapping features of the first 2 categories. International Federation of Gynecology and Obstetrics (FIGO) stage was available in 31 cases: 15 were stage la, 6 stage Ic, 2 stage II, 7 stage III, and I stage IV. Follow-up was obtained in 21 cases. Seven patients died of the disease after a median time of 8 months: 3 stage IC, I stage II, I stage III, I stage IV, and the other was unstaged. Ten patients were alive and clinically free of disease after a median follow-up of 5 years: they were all stage Ia. Three patients (2 stages III and I stage IV) were alive with disease at 3 years, 9 months, and 7 months. The other patient (stage Ia) died of an unrelated cause. Thus, only I patient with stage Ia disease died, and she died of causes other than ovarian cancer. The presence of foci/nodules of anaplastic carcinoma in unruptured stage I mucinous tumors of the ovary does not necessarily carry an adverse prognosis. These foci/ nodules may exhibit rhabdoid, sarcomatoid (spindle cell), or pleomorphic features. C1 [Provenza, Claudia; Prat, Jaime] Autonomous Univ Barcelona, Hosp Santa Creu & San Pau, Dept Pathol, Barcelona 08025, Spain. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Prat, J (reprint author), Autonomous Univ Barcelona, Hosp Santa Creu & San Pau, Dept Pathol, St Antoni Ma Claret 167, Barcelona 08025, Spain. EM jprat@santpau.es RI Prat, Jaime/G-4679-2011 NR 25 TC 34 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2008 VL 32 IS 3 BP 383 EP 389 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 270TH UT WOS:000253742600005 PM 18300813 ER PT J AU Thiagalingam, S Johnson, MM Colby, KA Zenibowicz, A AF Thiagalingam, Sureka Johnson, Matthew M. Colby, Kathryn A. Zenibowicz, Artur TI Juvenile conjunctival nevus - Clinicopothologic analysis of 33 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE conjunctiva; nevus; melanoma ID PRIMARY ACQUIRED MELANOSIS; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; FEATURES; TUMORS AB Conjunctival nevi in children and adolescents often have histologic features that can be difficult to differentiate from malignancy. We have identified a subset of childhood nevi displaying a confluent growth pattern and a lack of maturation that we have defined as juvenile conjunctival nevi (JCN), with the aim of further describing the clinicopathologic features of these lesions. Lesions identified as conjunctival nevus in a tertiary referral hospital were reviewed and the subset of lesions identified as JCN were further evaluated. Clinical details including follow-up data were also gathered. Of the 40 conjunctival nevi identified, 33 fit the criteria for JCN. The mean age at time of excision was 10.9 years (range: 4 to 19 y). Thirty-two lesions were of the compound type; one was a junctional nevus. All showed a nested junctional growth pattern. In 17 lesions (61 %), the junctional component extended beyond the subepithelial component (shoulder phenomenon). Maturation was absent in 21 of the compound nevi (66%, average age 10.3 y), and incomplete in the remaining 11 lesions (34%, average age 12.1 y). The nuclei of the subepithelial nevus cells were larger than the epithelial nevus cells in 19 nevi (59%) and the same size in 13 (41 %). A lymphocytic host response was present in 17 lesions (52%). Mitotic figures were rarely seen. None of the lesions had recurred over an average follow-up period of 34 months. Recognition of JCN as a distinct morphologic variant of a conjunctival nevus with characteristic histologic features may help to distinguish this benign lesion from melanoma. C1 [Thiagalingam, Sureka; Colby, Kathryn A.; Zenibowicz, Artur] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Thiagalingam, Sureka; Johnson, Matthew M.; Colby, Kathryn A.; Zenibowicz, Artur] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Johnson, Matthew M.; Zenibowicz, Artur] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Zenibowicz, A (reprint author), Lahey Clin Fdn, Dept Pathol, Burlington, MA 01805 USA. EM dr.z@DermatopathologyConsultations.com NR 29 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2008 VL 32 IS 3 BP 399 EP 406 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 270TH UT WOS:000253742600007 PM 18300811 ER PT J AU Coston, WMP Loera, S Lau, SK Ishizawa, S Jiang, Z Wu, CL Yen, Y Weiss, LM Chu, PG AF Coston, Wanda M. P. Loera, Sofia Lau, Sean K. Ishizawa, Shin Jiang, Zhong Wu, Chin-Lee Yen, Yun Weiss, Lawrence M. Chu, Peiguo G. TI Distinction of hepatocellular carcinoma from benign hepatic mimickers using glypican-3 and CD34 immunohistochemistry SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE hepatocellular carcinoma; hepatic adenoma; focal nodular hyperplasia; Glypican-3; CD34; immunohistochemistry ID GOLABI-BEHMEL-SYNDROME; ENDOTHELIAL-CELLS; DIAGNOSTIC-VALUE; DYSPLASTIC NODULES; TUMOR-MARKER; WILMS-TUMOR; EXPRESSION; LIVER; PROTEOGLYCANS; OVERGROWTH AB Distinguishing a well-differentiated hepatocellular carcinoma (HCC) from normal and cirrhotic liver tissue or benign liver nodules, such as hepatic adenoma (HA) and focal nodular hyperplasia (FNH), may be very difficult in some cases, particularly in small needle core biopsies. We studied the expression of Glypican-3 (GPC3) and CD34 in 107 cases of HCC, 19 cases of HA, and 16 cases of focal nodular hyperplasia (FNH). In addition, we studied GPC3 expression in 225 cases of nonhepatic human tumors with epithelial differentiation. Ninety-four of 107 cases (88%) of HCC showed focal or diffuse cytoplasmic GPO staining, whereas all HA and FNH cases were GPC3-negative, and only 7 of 225 cases (3%) of nonhepatic tumors with epithelial differentiation expressed GPC3. The sensitivity and specificity of GPC3 for HCC was 88% and 97%, respectively. There were three CD34 staining patterns observed in hepatic tissue: negative, incomplete positive, and complete positive. In negative staining pattern, only blood vessels in portal triads or rare sinusoidal spaces immediately adjacent to portal tracts were positive. The negative staining pattern was seen in normal or cirrhotic liver tissue only. The complete CD34 staining pattern showed virtually all sinusoidal spaces with CD34-positive staining throughout the lesion. The complete CD34 staining pattern was seen in virtually all cases of HCC and in only some cases of HA and FNH. The incomplete CD34 staining pattern was characterized by either CD34 positivity in virtually all sinusoidal spaces in some but not all nodules or CD34 positivity in the peripheral sinusoidal spaces adjacent to portal triads. The incomplete CD34 staining pattern was seen in rare cases of HCC and in most cases of HA and FNH. We conclude that GPC3 is a very specific marker not only for differentiating HCC from nonhepatic tumors with epithelial differentiation, but also for differentiating HCC from HA and FNH. GPC3 immunoreactivity, in combination with a complete CD34 immunostaining pattern, greatly facilitates the accuracy of distinguishing between malignant hepatic lesions and benign mimickers. C1 [Coston, Wanda M. P.; Loera, Sofia; Lau, Sean K.; Weiss, Lawrence M.; Chu, Peiguo G.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Yen, Yun] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. [Ishizawa, Shin] Toyama Med Pharmaceut Univ Hosp, Dept Pathol, Toyama, Japan. [Jiang, Zhong] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Chu, PG (reprint author), City Hope Natl Med Ctr, Div Pathol, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM pchu@coh.org NR 34 TC 70 Z9 79 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2008 VL 32 IS 3 BP 433 EP 444 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 270TH UT WOS:000253742600012 PM 18300806 ER PT J AU Buell, JF Daily, P McBride, MA Chapman, JR Delmonico, F AF Buell, J. F. Daily, P. McBride, M. A. Chapman, J. R. Delmonico, F. TI H. Myron Kaufman (1933-2007) medical director and senior scientist of UNOS: Transplant surgeon and friend SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Biographical-Item C1 [Buell, J. F.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA. [Daily, P.; McBride, M. A.] UNOS, Richmond, KY USA. [Chapman, J. R.] Univ Sydney, Dept Intervent Med, Sydney, NSW 2006, Australia. [Delmonico, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Buell, JF (reprint author), Univ Louisville, Dept Surg, Louisville, KY 40292 USA. EM joseph.buell@louisville.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2008 VL 8 IS 3 BP 719 EP 720 DI 10.1111/j.1600-6143.2007.02102.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 267IV UT WOS:000253503600036 ER PT J AU Fiellin, DA Moore, BA Sullivan, LE Becker, WC Pantalon, MV Chawarski, MC Barry, DT O'Connor, PG Schottenfeld, RS AF Fiellin, David A. Moore, Brent A. Sullivan, Lynn E. Becker, William C. Pantalon, Michael V. Chawarski, Marek C. Barry, Declan T. O'Connor, Patrick G. Schottenfeld, Richard S. TI Long-term treatment with buprenorphine/naloxone in primary care: Results at 2-5 years SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID OPIOID DEPENDENCE; METHADONE-MAINTENANCE; FOLLOW-UP; HEROIN DEPENDENCE; RANDOMIZED-TRIAL; ADDICTION; RETENTION; OUTCOMES; HEPATITIS; NALOXONE AB To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases. and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment. C1 [Fiellin, David A.; Sullivan, Lynn E.; O'Connor, Patrick G.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Moore, Brent A.; Pantalon, Michael V.; Chawarski, Marek C.; Barry, Declan T.; Schottenfeld, Richard S.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Becker, William C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Fiellin, DA (reprint author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St,POB 208025, New Haven, CT 06520 USA. EM david.fiellin@yale.edu RI barry, declan/G-4462-2011; Moore, Brent/O-4867-2015; OI Moore, Brent/0000-0003-0123-6616; Becker, William/0000-0002-0788-1467; Fiellin, David/0000-0002-4006-010X FU NIDA NIH HHS [K24 DA000445-03, K23 DA15144, R01 DA009803-07] NR 31 TC 65 Z9 66 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2008 VL 17 IS 2 BP 116 EP 120 DI 10.1080/10550490701860971 PG 5 WC Substance Abuse SC Substance Abuse GA 301MT UT WOS:000255901000005 PM 18393054 ER PT J AU Schwartzman, A Dougherty, RF Taylor, JE AF Schwartzman, Armin Dougherty, Robert F. Taylor, Jonathan E. TI FALSE DISCOVERY RATE ANALYSIS OF BRAIN DIFFUSION DIRECTION MAPS SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Diffusion tensor imaging; directional statistics; multiple testing; empirical null; spatial smoothing ID WHITE-MATTER AB Diffusion tensor imaging (DTI) is a novel modality of magnetic resonance imaging that allows noninvasive mapping, of the brain's white matter. A particular map derived from DTI measurements is a map of water principal diffusion directions, which are proxies for neural fiber directions. We consider a study in which diffusion direction maps were acquired for two groups of subjects. The objective of the analysis is to find regions of the brain in which the corresponding diffusion directions differ between the groups. This is attained by first computing, a test statistic for the difference in direction at every brain location using a Watson model for directional data. Interesting locations are Subsequently selected with control of the false discovery rate. More accurate modeling of the null distribution is obtained using all empirical null density based on the empirical distribution of the test statistics across the brain. Further, substantial improvements in power are achieved by local spatial averaging of the test statistic map. Although the focus is on one particular study and imaging technology, the proposed inference methods can be applied to other large scale simultaneous hypothesis testing problems with a continuous underlying spatial structure. C1 [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Dougherty, Robert F.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Taylor, Jonathan E.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM armins@hsph.harvard.edu; jonathan.taylor@stanford.edu; bobd@stanford.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU William R. and Sara Hart Kimball Stanford Graduate Fellowship; Schwab Foundation for Learning; NIH [EY-01-5000]; NSF [DMS-04-05970] FX Supported in part by a William R. and Sara Hart Kimball Stanford Graduate Fellowship.; Supported by the Schwab Foundation for Learning and NIH Grant EY-01-5000.; Supported by NSF Grant DMS-04-05970. NR 21 TC 34 Z9 34 U1 1 U2 2 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD MAR PY 2008 VL 2 IS 1 BP 153 EP 175 DI 10.1214/07-AOAS133 PG 23 WC Statistics & Probability SC Mathematics GA 374QB UT WOS:000261057700013 ER PT J AU Albers, AB Siegel, M Cheng, DM Biener, L Rigotti, NA AF Albers, Alison B. Siegel, Michael Cheng, Debbie M. Biener, Lois Rigotti, Nancy A. TI Household smoking bans and adolescent anti-smoking attitudes and smoking initiation: A longitudinal study SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Biener, Lois] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. EM aalbers@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S190 EP S190 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500740 ER PT J AU Berg, CJ Park, ER Chang, Y Rigotti, NA AF Berg, Carla J. Park, Elyse R. Chang, Yuchiao Rigotti, Nancy A. TI Is concern about post-cessation weight gain a barrier to smoking cessation among pregnant women? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Berg, Carla J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Berg, Carla J.; Park, Elyse R.; Chang, Yuchiao; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. EM cjberg@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S99 EP S99 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500381 ER PT J AU Cully, JA Phillips, LL Stanley, M Kunik, ME AF Cully, Jeffrey A. Phillips, Laura L. Stanley, Melinda Kunik, Mark E. TI Depression, anxiety, and quality of life in congestive heart failure SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cully, Jeffrey A.; Stanley, Melinda; Kunik, Mark E.] Baylor Coll Med, Houston, TX 77030 USA. [Cully, Jeffrey A.; Phillips, Laura L.; Kunik, Mark E.] Michael DeBakey Med Ctr, Houston, TX USA. EM jcully@bcm.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S165 EP S165 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500644 ER PT J AU Emmons, KM AF Emmons, Karen M. TI Long-term smoking cessation outcomes among childhood cancer survivors in the partnership for health study SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S10 EP S10 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500035 ER PT J AU Gonzalez, JS Safren, S Cagliero, E Wexler, D Meigs, J Grant, R AF Gonzalez, Jeffrey S. Safren, Steven Cagliero, Enrico Wexler, Deborah Meigs, James Grant, Richard TI Symptoms of depression prospectively predict poorer self-care and adherence in patients with type 2 diabetes SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gonzalez, Jeffrey S.; Safren, Steven] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gonzalez, Jeffrey S.; Safren, Steven; Cagliero, Enrico; Wexler, Deborah; Meigs, James; Grant, Richard] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Cagliero, Enrico; Wexler, Deborah] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Meigs, James; Grant, Richard] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. EM jsgonzalez@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S43 EP S43 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500160 ER PT J AU Greer, J Temel, J Pirl, W AF Greer, Joseph Temel, Jennifer Pirl, William TI Psychological determinants of aggressive care at the end of life in patients with advanced non-small-cell lung cancer SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Temel, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. EM jgreer2@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S73 EP S73 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500283 ER PT J AU Harper, F Levy, AG Gleason, M Coyne, J Armstrong, K AF Harper, Felicity Levy, Andrea Gurmankin Gleason, Marci Coyne, James Armstrong, Katrina TI Role of spouse supportive coping in treatment decision-making for prostate cancer patients SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Harper, Felicity; Gleason, Marci] Karmanos Canc Inst, Detroit, MI USA. [Levy, Andrea Gurmankin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Coyne, James; Armstrong, Katrina] Abramson Canc Ctr, Philadelphia, PA USA. EM harperf@karmanos.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S172 EP S172 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500669 ER PT J AU Merritt, M Roethel, A Roche, K Edwards, CL Bennett, GG Koenig, HG Abdullah, M AF Merritt, Marcellus Roethel, Angela Roche, Kelly Edwards, Christopher L. Bennett, Gary G. Koenig, Harold G. Abdullah, Muneebah TI A non-linear role of religiosity in cardiovascular reactivity to personally-relevant stress? The moderating role of educational attainment SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Merritt, Marcellus; Roethel, Angela; Roche, Kelly; Abdullah, Muneebah] U Wisconsin Milwaukee, Milwaukee, WI USA. [Edwards, Christopher L.; Koenig, Harold G.] Duke Univ, Med Ctr, Durham, NC USA. [Bennett, Gary G.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM merrittm@uwm.edu RI Koenig, Harold/F-7379-2011 NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S127 EP S127 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500492 ER PT J AU Mimiaga, M Reisner, S Bertrand, T Cranston, K VanDerwarker, R Novak, D Mayer, K AF Mimiaga, Matthew Reisner, Sari Bertrand, Tom Cranston, Kevin VanDerwarker, Rodney Novak, David Mayer, Kenneth TI Crystal methamphetamine use and HIV/STI risk behavior among massachusetts MSM: Implications for intervention development SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mimiaga, Matthew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Bertrand, Tom; Cranston, Kevin; Novak, David] MDPH, Boston, MA USA. [Mayer, Kenneth] Brown Univ, Providence, RI 02912 USA. EM mmimiaga@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S136 EP S136 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500529 ER PT J AU Myaskovsky, L Dew, MA Switzer, GE Hritz, V Ramkumar, M Shapiro, R AF Myaskovsky, Larissa Dew, Mary Amanda Switzer, Galen E. Hritz, Victoria Ramkumar, Mohan Shapiro, Ron TI Cultural factors and transplant knowledge related to race disparities in living donor kidney transplantation SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Myaskovsky, Larissa; Dew, Mary Amanda; Switzer, Galen E.; Shapiro, Ron] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. EM myaskovskyl@upmc.edu NR 0 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S56 EP S56 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500214 ER PT J AU Psaros, C Rigotti, N Park, E AF Psaros, Christina Rigotti, Nancy Park, Elyse TI Exploring how negative mood contributes to postpartum relapse to smoking SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Psaros, Christina; Rigotti, Nancy; Park, Elyse] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cpsaros@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S99 EP S99 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500382 ER PT J AU Quintiliani, LM Allen, JD Marino, M Li, Y AF Quintiliani, Lisa M. Allen, Jennfier D. Marino, Miguel Li, Yi TI Multiple cancer-related health risk behaviors among female college students SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Quintiliani, Lisa M.; Marino, Miguel; Li, Yi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Allen, Jennfier D.; Marino, Miguel; Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennfier D.] William Connell Sch Nursing, Boston, MA USA. EM lisa_quintilianI@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500246 ER PT J AU Yi, JP Smith, R Vitaliano, P Yi, J Mai, S Hillman, M Weinger, K AF Yi, Joyce P. Smith, Ronald Vitaliano, Peter Yi, Jean Mai, Scarlett Hillman, Matthew Weinger, Katie TI A person-focused analysis of resilience resources and coping in diabetes patients SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Yi, Joyce P.] Childrens Hosp & Reg Med Ctr, Seattle, WA 98105 USA. [Smith, Ronald; Vitaliano, Peter; Yi, Jean; Mai, Scarlett; Hillman, Matthew] Univ Washington, Seattle, WA 98195 USA. [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM joyce.yi@seattlechildrens.org NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2008 VL 35 SU 1 BP S82 EP S82 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 348YH UT WOS:000259245500319 ER PT J AU Sun, BC Hoffman, JR Mower, WR Shiamovitz, GZ Gabayan, GZ Mangione, CM AF Sun, Benjamin C. Hoffman, Jerome R. Mower, William R. Shiamovitz, Gil Z. Gabayan, Gelarah Z. Mangione, Carol M. TI Low diagnostic yield of electrocardiogram testing in younger patients with syncope SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENTS; OUTCOMES; RULE; CARE AB Study objective: Routine ECG testing is recommended in the evaluation of syncope, although the value of such testing in young patients is unclear. For ECG testing, we assess the diagnostic yield (frequency that ECG identified the reason for syncope) and predictive accuracy for 14-day cardiac events after an episode of syncope as a function of age. Methods: Adult patients with syncope or near-syncope were prospectively enrolled for 1 year at a single academic emergency department (ED). A 3-physician panel reviewed ED charts, hospital records, and telephone interview forms to identify predefined cardiac events. The primary outcome included all 14-day, predefined cardiac events including arrhythmia, myocardial ischemia, and structural heart disease. Results: Of 592 eligible patients, 477 (81%) provided informed consent. Direct telephone contact or admission/outpatient records were successfully obtained for 461 (97%) patients, who comprised the analytic cohort. There were 44 (10%) patients who experienced a 14-day cardiac event. Overall diagnostic yield of ECG testing was 4% (95% confidence interval 2% to 6%). For patients younger than 40 years, ECG testing had a diagnostic yield of 0% (95% confidence interval 0% to 3%) and was associated with a 10% frequency of abnormal findings. Conclusion: ECG testing in patients younger than 40 years did not reveal a cardiac cause of syncope and was associated with a significant frequency of abnormal ECG findings unrelated to syncope. Although our findings should be verified in larger studies, it may be reasonable to defer ECG testing in younger patients who have a presentation consistent with a benign cause of syncope. C1 [Sun, Benjamin C.] W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. [Sun, Benjamin C.; Mangione, Carol M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Hoffman, Jerome R.; Mower, William R.; Shiamovitz, Gil Z.; Gabayan, Gelarah Z.] Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. [Mangione, Carol M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Sun, BC (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Off 3214A,Mail Stop 111,Bldg 500,Wing 3E,11301 Wi, Los Angeles, CA 90073 USA. EM bsun@post.harvard.edu FU NIA NIH HHS [AG 02-004, K12AG001004] NR 11 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2008 VL 51 IS 3 BP 240 EP 246 DI 10.1016/j.annemergmed.2007.04.006 PG 7 WC Emergency Medicine SC Emergency Medicine GA 270SA UT WOS:000253739300004 PM 17559972 ER PT J AU Pallin, DJ Egan, DJ Pelletier, AJ Espinola, JA Hooper, DC Camargo, CA AF Pallin, Daniel J. Egan, Daniel J. Pelletier, Andrea J. Espinola, Janice A. Hooper, David C. Camargo, Carlos A., Jr. TI Increased US emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EPIDEMIOLOGY; POPULATION; CELLULITIS AB Study objective: Test the hypotheses that emergency department (ED) visits for skin and soft tissue infections became more frequent during the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), and that antibiotics typically active against community-associated MRSA were chosen increasingly. Methods: From merged National Hospital Ambulatory Medical Care Survey data for 1993-2005, we identified ED visits with diagnosis of cellulitis, abscess, felon, impetigo, hidradenitis, folliculitis, infective mastitis, nonpurulent mastitis, breast abscess, or carbuncle and furuncle. Main outcomes were change over time in rate of ED visits with such a diagnosis and proportion of antibiotic regimens including an agent typically active against community-associated MRSA. We report national estimates derived from sample weights. We tested trends with least squares linear regression. Results: In 1993, infections of interest were diagnosed at 1.2 million visits (95% confidence interval [CI] 0.96 to 1.5 million) versus 3.4 million in 2005 (95% Cl 2.8 to 4.1 million; P for trend <.001). As a proportion of all ED visits, such infections were diagnosed at 1.35% in 1993 (95% Cl 1.07% to 1.64%) versus 2.98% in 2005 (95% Cl 2.40% to 3.56%; P for trend <.001). When antibiotics were prescribed at such visits, an antibiotic typically active against community-associated MRSA was chosen rarely from 1993 to 2001 but increasingly thereafter, reaching 38% in 2005 (95% Cl 30% to 45%; P for trend <.001). In 2005, trimethoprim-sulfamethoxazole was used in 51% of regimens Conclusion: US ED visits for skin and soft tissue infections increased markedly from 1993 to 2005, contemporaneously with the emergence of community-associated MRSA. ED clinicians prescribed more antibiotics typically active against community-associated MRSA, especially trimethoprim-sulfamethoxazole. Possible confounders are discussed, such as increasing diabetes or shifts in locus of care. C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Egan, Daniel J.] St Vincent Hosp Manhattan, Dept Emergency Med, New York, NY USA. [Egan, Daniel J.] St Vincent Hosp Manhattan, Sect Comprehens HIV Med, Dept Med, New York, NY USA. [Pelletier, Andrea J.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 14 TC 198 Z9 199 U1 0 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2008 VL 51 IS 3 BP 291 EP 298 DI 10.1016/j.annemergmed.2007.12.004 PG 8 WC Emergency Medicine SC Emergency Medicine GA 270SA UT WOS:000253739300012 PM 18222564 ER PT J AU Colleoni, M Viale, G Zahrieh, D Bottiglieri, L Gelber, RD Veronesi, P Balduzzi, A Torrisi, R Luini, A Intra, M Dellapasqua, S Cardillo, A Ghisini, R Peruzzotti, G Goldhirsch, A AF Colleoni, M. Viale, G. Zahrieh, D. Bottiglieri, L. Gelber, R. D. Veronesi, P. Balduzzi, A. Torrisi, R. Luini, A. Intra, M. Dellapasqua, S. Cardillo, A. Ghisini, R. Peruzzotti, G. Goldhirsch, A. TI Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; predictive factors; prognostic factors; primary chemotherapy ID EPIDERMAL-GROWTH-FACTOR; OPERABLE BREAST-CANCER; PATHOLOGICAL COMPLETE RESPONSE; FACTOR RECEPTOR EXPRESSION; STEROID-HORMONE RECEPTORS; ESTROGEN-RECEPTOR; NEOADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTOR; PRIMARY TUMOR; THERAPY AB Purpose: To identify the role of estrogen (ER), progesterone (PgR), epidermal growth factor 1 (HER1), and HER2 receptors in predicting response to preoperative chemotherapy. Materials and methods: We reviewed the pretreatment biopsies of 485 patients with locally advanced breast cancer (cT2-T4, N0-2, M0) treated with preoperative chemotherapy. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to clinical and pathological findings including ER/PgR status (absent versus expressed), HER1 (absent versus expressed) and HER2 (overexpressed versus none) expression. Results: Patients with ER/PgR-absent tumors were 12.0 times [95% confidence interval (CI) 4.93-29.28] more likely to achieve a pCR (P < 0.0001). Predictors of disease-free survival (DFS) at the univariate analysis included HER1 [hazards ratio (HR) 1.6, 95% CI 1.04-2.32, P = 0.03] and HER2 (HR 1.6, 95% CI 1.08-2.38, P = 0.02) expression. A statistically significant difference in DFS was confirmed at the multivariate analysis for patients with ER/PgR-absent disease (HR 2.1, 95% CI 1.41-2.99, P = 0.0002). Conclusions: The pCR rate is higher and outcome worse for patients with ER/PgR-absent tumors. HER1 and HER2 expression may have a prognostic role in locally advanced breast cancer and warrant further studies. C1 [Colleoni, M.; Balduzzi, A.; Torrisi, R.; Dellapasqua, S.; Cardillo, A.; Ghisini, R.] European Inst Oncol, Dept Med, Div Med Oncol, Unit Res Med Senol, I-20141 Milan, Italy. [Viale, G.; Veronesi, P.; Luini, A.] Univ Milan, Sch Med, Milan, Italy. [Viale, G.; Bottiglieri, L.] European Inst Oncol, Div Pathol, Milan, Italy. [Zahrieh, D.; Bottiglieri, L.] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. [Zahrieh, D.; Gelber, R. D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Peruzzotti, G.; Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Veronesi, P.; Luini, A.; Intra, M.] European Inst Oncol, Div Senol, Milan, Italy. RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Div Med Oncol, Unit Res Med Senol, Via Riparnonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it FU NCI NIH HHS [CA-75362] NR 30 TC 64 Z9 72 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2008 VL 19 IS 3 BP 465 EP 472 DI 10.1093/annonc/mdm509 PG 8 WC Oncology SC Oncology GA 270UR UT WOS:000253746200010 PM 17986623 ER PT J AU Hoffman, WD Czyz, Y McCollum, DA Hursting, MJ AF Hoffman, William D. Czyz, Yvonne McCollum, David A. Hursting, Marcie J. TI Reduced argatroban doses after coronary artery bypass graft surgery SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 41st Midyear Clinical Meeting of the American-Society-of-Health-System-Pharmacists CY DEC 03-07, 2006 CL Anaheim, CA SP Amer Soc Hlth Syst Pharmacists DE argatroban; coronary artery bypass graft; heparin-induced thrombocytopenia ID HEPARIN-INDUCED THROMBOCYTOPENIA; CARDIOPULMONARY BYPASS; CARDIOVASCULAR-SURGERY; RENAL-FUNCTION; ANTICOAGULATION; THERAPY; DYSFUNCTION; PHARMACODYNAMICS; ANTIBODIES; CLEARANCE AB BACKGROUND: The Food and Drug Administration-approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 mu g/kg/min (0.5 mu g/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5-3 times baseline. Recent data suggest that reduced doses are required after cardiovascular surgery. OBJECTIVE: To characterize dosing requirements, aPTTs, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft (CABG) surgery. METHODS: Charts of 39 patients who underwent CABG surgery and were administered argatroban postoperatively for laboratory-confirmed HIT (n = 25), antibody-negative suspected HIT (n = 10), or previous HIT requiring anticoagulation (n = 4) were retrospectively reviewed. Patient characteristics, argatroban dosing information, aPTTs (target range 45-90 sec), and outcomes were summarized. Regression analyses explored potential effectors of dosage. RESULTS: Patient features, argatroban dosing patterns, and aPTTs were similar among groups. Many patients had laboratory evidence of some hepatic and/or renal dysfunction (median [range] bilirubin 1.0 [0.3-8.0] mg/dL, creatinine clearance 47 [18-287] mL/min). Overall, median argatroban doses were 0.5 mu g/kg/min initially and 0.6 mu g/kg/min during therapy (median duration 5.3 days). After argatroban initiation, aPTTs were greater than 90 seconds at first assessment in 4 patients (3 with abnormal hepatic function test results) initially administered 0.5, 1, 2, and 2 mu g/kg/min, respectively. Within approximately 16 hours of therapy, 33 (85%) patients achieved consecutive therapeutic aPTTs. No association was detected between mean dose during therapy and preoperative ejection fraction, routine hepatic or renal function test results (other than blood urea nitrogen [BUN]), or surgery type. A clinically insignificant association existed between dose and BUN: there was an approximately 0.15 mu g/kg/min dose decrease for each 10 mg/dL BUN increase. One patient developed thrombosis, 1 underwent finger amputation, 7 died (5 after argatroban cessation), and 4 had significant bleeding. CONCLUSIONS: These findings suggest: that reduced initial argatroban doses (eg, 0.5 mu g/kg/min), adjusted to achieve therapeutic aPTTs, provide rapid, adequate anticoagulation in postoperative CABG patients with presumed or previous HIT Prospective study of reduced initial dosing in this setting is warranted. C1 [Hursting, Marcie J.] Clin Sci Consulting, Austin, TX 78746 USA. [Hoffman, William D.] Massachusetts Gen Hosp, Div Cardiac Surg, Cardiac Surg Intens Care Unit, Boston, MA 02114 USA. [Czyz, Yvonne] Johns Hopkins Univ Hosp, Dept Pharm, Baltimore, MD 21287 USA. [Czyz, Yvonne] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [McCollum, David A.] CTI Clin Trial & Consulting Serv, Cincinnati, OH USA. RP Hursting, MJ (reprint author), Clin Sci Consulting, 3001 Loveland Cove, Austin, TX 78746 USA. EM mhursting@sprintmail.com NR 30 TC 22 Z9 22 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2008 VL 42 IS 3 BP 309 EP 316 DI 10.1345/aph.1K434 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274KM UT WOS:000254000200001 PM 18303137 ER PT J AU Mauldin, PD Salgado, CD Durkalski, VL Bosso, JA AF Mauldin, Patrick D. Salgado, Cassandra D. Durkalski, Valerie L. Bosso, John A. TI Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus: Relationships with antibiotic use and cost drivers SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 14-17, 2007 CL Denver, CO SP Amer Coll Clin Pharm DE antibiotic use; cost; methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococcus ID RISK-FACTORS; BACTEREMIA; FAECIUM; MORTALITY; OUTCOMES; CARE AB BACKGROUND: Increased incidence of nosocomial infections due to methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) has been associated with the use of certain antibiotics and has resulted in increased morbidity, mortality, and costs of care. OBJECTIVE: To describe relationships between vancomycin and linezolid use and incidence of these nosocomial infections over time and to determine factors associated with the increased costs of care (cost drivers) associated with affected patients. METHODS: The association between institution-wide antibiotic use and the rate of nosocomial MRSA and VRE infections was assessed using segmented regression analysis for interrupted time series. The effect that patient characteristics and procedures, as well as certain antibiotic use, had on costs and length of stay of patients with MRSA or VRE nosocomial infection was also assessed and cost drivers for the 2 types of infections were compared. RESULTS: Our analysis included 206 patients who developed MRSA (n = 187) or VRE (n = 19) nosocomial infection. Although small numbers of VRE nosocomial infection may limit generalizations from our results, we found no significant relationship between vancomycin or linezolid use and the rate of either infection. While mean hospital costs were similar, cost drivers varied somewhat between infection types. CONCLUSIONS: The incidence of MRSA or VRE infections does not appear to be related to the use of vancomycin or linezolid. Costs of care are quite high in some affected patients and, while mean total hospital costs are similar, cost drivers appear to differ between the 2 infection types. C1 [Bosso, John A.] Med Univ S Carolina, S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, S Carolina Coll Med,Div Infect Dis, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Med Univ S Carolina, Coll Pharm, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Ralph H Johnson Affairs Med Ctr, Charleston, SC USA. [Salgado, Cassandra D.] Med Univ S Carolina, Coll Med, Div Infect Dis, Charleston, SC USA. [Durkalski, Valerie L.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC USA. RP Bosso, JA (reprint author), Med Univ S Carolina, S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, S Carolina Coll Med,Div Infect Dis, 280 Calhoun St,POB 250144, Charleston, SC 29425 USA. EM bossoja@musc.edu NR 17 TC 8 Z9 8 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2008 VL 42 IS 3 BP 317 EP 326 DI 10.1345/aph.1K501 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274KM UT WOS:000254000200002 PM 18285560 ER PT J AU Bilimoria, KY Talamonti, MS Tomlinson, JS Stewart, AK Winchester, DP Ko, CY Bentrem, DJ AF Bilimoria, Karl Y. Talamonti, Mark S. Tomlinson, James S. Stewart, Andrew K. Winchester, David P. Ko, Clifford Y. Bentrem, David J. TI Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors - Analysis of 3851 patients SO ANNALS OF SURGERY LA English DT Article ID LONG-TERM SURVIVAL; ISLET-CELL-CARCINOMA; ENDOCRINE TUMORS; SURGICAL EXPERIENCE; HOSPITAL VOLUME; STAGING SYSTEM; UNITED-STATES; CANCER; SURGERY; OUTCOMES AB Background: Pancreatic neuroendocrine tumors (PNET) have a poorly defined natural history, and a staging system is not available . The objective of this study was to identify factors predicting survival after pancreatectomy for PNETs and to establish a postresection prognostic score. Patients and Methods: From the National Cancer Data Base (1985-2004), patients were identified who underwent PNET resection. Multivariable Cox proportional hazards modeling was used to assess the impact of patient, tumor, treatment, and hospital factors on survival. A prognostic score based on the predictive factors from the Cox model was developed. Results: Three thousand eight hundred fifty-one patients underwent resection for PNETs. Five-year overall survival was 59.3%, and the 10-year survival was 37.7%. On multivariable analysis, age, grade, distant metastases, tumor functionality, and type of resection were independent predictors of survival after resection of PNETs (P < 0.0001). Gender, race, socioeconomic status, tumor size, nodal status, margins, adjuvant chemotherapy, and hospital volume were not associated with survival. Age, grade, and distant metastases were the most significant predictors of survival and were incorporated into a PNET postresection prognostic score. The prognostic score correlated with outcomes and offered excellent survival discrimination by each of the 3 score subgroups: 76.7%, 50.9%, and 35.7% (P < 0.0001). The concordance index was 0.63 (95% CI 0.59-0.67), indicating reasonable agreement between actual outcomes and that predicted by the prognostic score. Conclusions: The prognostic score can be used to predict outcomes, guide adjuvant treatment, and stratify patients for clinical trials. C1 [Bilimoria, Karl Y.; Talamonti, Mark S.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. [Bilimoria, Karl Y.; Stewart, Andrew K.; Winchester, David P.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Talamonti, Mark S.; Winchester, David P.] Evanston NW Healthcare, Dept Surg, Evanston, IL USA. [Tomlinson, James S.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Tomlinson, James S.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), NW Mem Hosp, Dept Surg, 251 E Huron St,Galter 3-150, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 68 TC 123 Z9 127 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2008 VL 247 IS 3 BP 490 EP 500 DI 10.1097/SLA.0b013e31815b9cae PG 11 WC Surgery SC Surgery GA 266LH UT WOS:000253436200015 PM 18376195 ER PT J AU Kelz, RR Freeman, KM Hosokawa, PW Asch, DA Spitz, FR Moskowitz, M Henderson, WG Mitchell, ME Itani, KMF AF Kelz, Rachel R. Freeman, Kathryn M. Hosokawa, Patrick W. Asch, David A. Spitz, Francis R. Moskowitz, Miriam Henderson, William G. Mitchell, Marc E. Itani, Kamal M. F. TI Time of day is associated with, postoperative morbidity - An analysis of the National Surgical Quality Improvement Program Data SO ANNALS OF SURGERY LA English DT Article ID ADVERSE EVENTS; RISK ADJUSTMENT; MALPRACTICE CLAIMS; PATIENT SAFETY; CARE; MORTALITY; OUTCOMES; ERRORS; COLORADO; SURGERY AB Objective: To examine the association between surgical start time and morbidity and mortality for nonemergent procedures. Summary Background Data: Patients require medical services 24 hours a day. Several studies have demonstrated a difference in outcomes over the course of the day for anesthetic adverse events, death in the ICU, and dialysis care. The relationship between operation start time and patient outcomes is yet undefined. Methods: We performed a retrospective cohort study of 144,740 nonemergent general and vascular surgical procedures performed within the VA Medical System 2000-2004 and entered into the National Surgical Quality Improvement Program Database. Operation start time was the independent variable of interest. Logistic regression was used to adjust for patient and procedural characteristics and to determine the association between start time and, in 2 independent models, mortality and morbidity. Results: Unadjusted later start time was significantly associated with higher surgical morbidity and mortality. After adjustment for patient and procedure characteristics, mortality was not significantly associated with start time. However, after appropriate adjustment, operations starting between 4 Pm and 6 Pm were associated with an elevated risk of morbidity (OR = 1.25, P <= 0.005) over those starting between 7 Am and 4 Pm as were operations starting between 6 Pm and 11 Pm (OR = 1.60, P <= 0.005). Conclusions: When considering a nonemergent procedure, surgeons must bear in mind that cases that start after routine "business" hours within the VA System may face an elevated risk of complications that warrants further evaluation. C1 [Kelz, Rachel R.; Spitz, Francis R.; Moskowitz, Miriam] VA Med Ctr Philadelphia, Dept Surg, Philadelphia, PA USA. [Kelz, Rachel R.; Freeman, Kathryn M.; Spitz, Francis R.] Hosp Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Hosokawa, Patrick W.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Aurora, CO USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ REs & Promot, Philadelphia, PA USA. [Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Mitchell, Marc E.] Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA. [Itani, Kamal M. F.] Boston VAHCS, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. RP Kelz, RR (reprint author), 3400 Spruce St,4 Silverstein, Philadelphia, PA 19104 USA. EM rapaporr@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X NR 56 TC 46 Z9 47 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2008 VL 247 IS 3 BP 544 EP 552 DI 10.1097/SLA.0b013e31815d7434 PG 9 WC Surgery SC Surgery GA 266LH UT WOS:000253436200022 PM 18376202 ER PT J AU Goss, PE AF Goss, Paul E. TI Addressing the future: combination with targeted therapies, adjuvant setting and beyond SO ANTI-CANCER DRUGS LA English DT Article; Proceedings Paper CT Conference on Dark Energy In the Universe CY SEP 01-04, 2007 CL Hakone, JAPAN DE adjuvant therapy; endocrine; targeted therapies; aromastase inhibitors; endocrine resistance ID AROMATASE INHIBITOR EXEMESTANE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; PHASE-III; LETROZOLE; RECEPTOR; TAMOXIFEN; GROWTH; BONE AB The potential mechanisms of de novo and acquired resistance to endocrine therapy are increasingly being understood and potential treatment options that offer a therapeutic alternative in patients exhibiting resistance are being explored. Any efforts directed towards improving patient outcomes beyond aromatase inhibitors (Als) in the adjuvant setting are likely to be focused on blocking endocrine and other pathways simultaneously, either upfront or in sequence. In particular, targeted therapies either alone or in combination with Als may improve clinical outcomes - the results of ongoing clinical trials will shape the future treatment of breast cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 16 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD MAR PY 2008 VL 19 SU 2 BP S3 EP S5 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 297JZ UT WOS:000255614300002 PM 18337641 ER PT J AU Huyghe, A Francois, P Charbonnier, Y Tangomo-Bento, M Bonetti, EJ Paster, BJ Bolivar, I Baratti-Mayer, D Pittet, D Schrenzel, J AF Huyghe, Antoine Francois, Patrice Charbonnier, Yvan Tangomo-Bento, Manuela Bonetti, Eve-Julie Paster, Bruce J. Bolivar, Ignacio Baratti-Mayer, Denise Pittet, Didier Schrenzel, Jacques CA Geneva Study Grp Noma (GESNOMA) TI Novel Microarray design strategy to study complex bacterial communities SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA GENE; DETECTING MICROBIAL-POPULATIONS; 50-MER OLIGONUCLEOTIDE ARRAYS; CANCRUM ORIS NOMA; GUT MICROBIOME; DIVERSITY; IDENTIFICATION; ENVIRONMENT; VALIDATION; SEQUENCES AB Assessing bacterial flora composition appears to be of increasing importance to fields as diverse as physiology, development, medicine, epidemiology, the environment, and the food industry. We report here the development and validation of an original microarray strategy that allows analysis of the phylogenic composition of complex bacterial mixtures. The microarray contains similar to 9,500 feature elements targeting 16S rRNA gene-specific regions. Probe design was performed by selecting oligonucleotide sequences specific to each node of the seven levels of the bacterial phylogenetic tree (domain, phylum, class, order, family, genus, and species). This approach, based on sequence information, allows analysis of the bacterial contents of complex bacterial mixtures to detect both known and unknown microorganisms. The presence of unknown organisms can be suspected and mapped on the phylogenetic tree, indicating where to refine analysis. Initial proof-of-concept experiments were performed on oral bacterial communities. Our results show that this hierarchical approach can reveal minor changes (<= 1%) in gingival flora content when samples collected in individuals from similar geographical origins are compared. C1 [Huyghe, Antoine; Francois, Patrice; Charbonnier, Yvan; Tangomo-Bento, Manuela; Bonetti, Eve-Julie; Schrenzel, Jacques] Univ Geneva Hosp, Genom Res Lab, Infect Dis Serv, CH-1211 Geneva 14, Switzerland. [Paster, Bruce J.] Forsyth Inst, Boston, MA USA. [Bolivar, Ignacio] Inst Angewandte Immunol, Zuchwil, Switzerland. [Baratti-Mayer, Denise] Plast & Reconstruct Surg, Fac Med, Geneva, Switzerland. [Pittet, Didier] Infect Control Program, Fac Med, Geneva, Switzerland. RP Huyghe, A (reprint author), Univ Geneva Hosp, Genom Res Lab, Infect Dis Serv, Micheli Crest 24, CH-1211 Geneva 14, Switzerland. EM antoine.huyghe@genomic.ch FU NIDCR NIH HHS [DE-11443, R01 DE011443] NR 52 TC 36 Z9 40 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2008 VL 74 IS 6 BP 1876 EP 1885 DI 10.1128/AEM.01722-07 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 275IR UT WOS:000254065600024 PM 18203854 ER PT J AU Smoller, JW Paulus, MP Fagerness, JA Purcell, S Yamaki, LH Hirshfeld-Becker, D Biederman, J Rosenbaum, JF Gelernter, J Stein, MB AF Smoller, Jordan W. Paulus, Martin P. Fagerness, Jesen A. Purcell, Shaun Yamaki, Lesley H. Hirshfeld-Becker, Dina Biederman, Joseph Rosenbaum, Jerrold F. Gelernter, Joel Stein, Murray B. TI Influence of RGS2 on anxiety-related temperament, personality, and brain function SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENERALIZED SOCIAL PHOBIA; CHILDHOOD BEHAVIORAL-INHIBITION; MAJOR DEPRESSIVE-DISORDERS; QUANTITATIVE-TRAIT LOCI; AMYGDALA ACTIVATION; NERVOUS-SYSTEM; 5-FACTOR MODEL; PANIC DISORDER; FACES; ASSOCIATION AB Context: Although anxiety disorders are heritable, their genetic and phenotypic complexity has made the identification of susceptibility genes difficult. Well-validated animal models and intermediate phenotypes provide crucial tools for genetic dissection of anxiety. The gene encoding regulator of G protein signaling 2 ( Rgs2) is a quantitative trait gene that influences mouse anxiety behavior, making its human ortholog ( RGS2) a compelling candidate gene for human anxiety phenotypes. Objective: To examine whether variation in RGS2 is associated with intermediate phenotypes for human anxiety disorders. Design: Family-based and case-control association analysis of single-nucleotide polymorphisms at the RGS2 locus in 3 independent samples. Setting: Massachusetts General Hospital, University of California, San Diego, and San Diego State University. Participants: Study participants included a family-based sample ( n=119 families) of children who underwent laboratory-based assessments of temperament ( behavioral inhibition), a sample of 744 unrelated adults who completed assessments of extraversion and introversion, and 55 unrelated adults who underwent functional magnetic resonance imaging measures of response to emotional faces. Main Outcome Measures: Laboratory-based behavioral measures of childhood temperament, self-report measure of personality, and functional magnetic resonance imaging response to emotion processing. Results: Markers spanning RGS2 were associated with childhood behavioral inhibition, a temperamental precursor of social anxiety disorder ( haplotype P= 3 x 10(-5); odds ratio, 2.99 in complete trios). In independent samples, RGS2 markers, including rs4606, which has previously been associated with RGS2 expression, were also associated with introversion ( a core personality trait in social anxiety disorder) and with increased limbic activation ( insular cortex and amygdala) during emotion processing ( brain phenotypes correlated with social anxiety). The genotype at rs4606 explained 10% to 15% of the variance in amygdala and insular cortex activation to emotional faces. Conclusions: These results provide the first evidence that a gene that influences anxiety in mice is associated with intermediate phenotypes for human anxiety disorders across multiple levels of assessment, including childhood temperament, adult personality, and brain function. This translational research suggests that some genetic influences on anxiety are evolutionarily conserved and that pharmacologic modulation of RGS2 function may provide a novel therapeutic approach for anxiety disorders. C1 [Smoller, Jordan W.; Fagerness, Jesen A.; Purcell, Shaun; Yamaki, Lesley H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. [Smoller, Jordan W.; Fagerness, Jesen A.; Purcell, Shaun; Yamaki, Lesley H.; Hirshfeld-Becker, Dina; Rosenbaum, Jerrold F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Smoller, Jordan W.; Yamaki, Lesley H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Paulus, Martin P.; Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, San Diego, CA USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet Psychiat, New Haven, CT USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, Div Human Genet Psychiat, New Haven, CT 06510 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, Div Human Genet Psychiat, New Haven, CT USA. RP Smoller, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu FU NIDA NIH HHS [R01 DA012849, DA12690, DA12849, DA15105, K24 DA015105]; NIMH NIH HHS [K-08 MH01770, K24 MH64122, R01 MH65413, R01MH47077-11] NR 59 TC 80 Z9 82 U1 5 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2008 VL 65 IS 3 BP 298 EP + DI 10.1001/archgenpsychiatry.2007.48 PG 13 WC Psychiatry SC Psychiatry GA 269TC UT WOS:000253672200007 PM 18316676 ER PT J AU Freedberor, DE Dave, J Kurth, T Gaziano, JM Bludau, JHA AF Freedberor, Daniel E. Dave, Jatin Kurth, Tobias Gaziano, J. Michael Bludau, Juergen H. A. TI Cognitive impairment over the age of 85: Hospitalization and mortality SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE geriatric patient; altered mental status; diagnostic decision making ID RANDOMIZED TRIAL; OLDER PERSONS; RISK-FACTORS; FOLLOW-UP; DELIRIUM; CARE; MANAGEMENT; DEMENTIA AB The risks of cognitive impairment among hospitalized patients over age 85 are not adequately understood. We used electronically recorded ICD-9 codes of inpatients over 85 years old to identify patients age :85 who showed signs of cognitive impairment during hospitalization it our institution. We randomly selected patient records showing cognitive impairment and patient control records matched for a-e and admission date but without cognitive impairment and obtained mortality information Lip to 18 months after discharge. Records were further examined to characterize hospital stay including reason for admission. After adjustment for comorbidities and potential confounders, patients over age 85 with ICD-9-defined cognitive impairment had increased risk of death within the hospital (hazard ratio (HR) = 3.99; 95% confidence interval (0) 0.42-37.90;p = 0.229), in the first year after hospitalization (HR = 2.35; 95% CI 1.15-4.78; p = 0.019), and cumulatively (HR = 2.46; 95% CI 1.26-4.82; p=0.009). In this matched cohort of hospitalized patients >= 85 years old, cognitive impairment was associated with an increased mortality rate. Because of this additional risk of death, hospitalized geriatric patients who are cognitively impaired may merit closer monitoring. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Freedberor, Daniel E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Freedberor, Daniel E.; Dave, Jatin; Kurth, Tobias; Gaziano, J. Michael; Bludau, Juergen H. A.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA. [Kurth, Tobias; Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Kurth, Tobias] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res Ctr, Boston, MA 02130 USA. RP Freedberor, DE (reprint author), 13 Symphony Rd,Apartment 8, Boston, MA 02115 USA. EM daniel_freedberg@hms.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 19 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD MAR-APR PY 2008 VL 46 IS 2 BP 137 EP 145 DI 10.1016/j.archger.2007.03.006 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 277JJ UT WOS:000254208200003 PM 17498822 ER PT J AU Jayadev, S Steinbart, EJ Chi, YY Kukull, WA Schellenberg, GD Bird, TD AF Jayadev, Suman Steinbart, Ellen J. Chi, Yueh-Yun Kukull, Walter A. Schellenberg, Gerard D. Bird, Thomas D. TI Conjugal Alzheimer disease - Risk in children when both parents have Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID GENE POLYMORPHISMS; OLDER PERSONS; ONSET; POPULATION; PREVALENCE; DEMENTIA; ASSOCIATION; PROJECTIONS AB Background: There is limited information regarding children's risk of Alzheimer disease (AD) if both parents are affected. Objective: To determine the risk of AD in families in which both parents have AD. Design: Retrospective study. Setting: University research center. Participants: A total of 111 families in which both parents had a clinical diagnosis of AD. Main Outcome Measure: Frequency of AD in the children of spouses with AD. Results: The 111 couples with AD had 297 children surviving to adulthood; 22.6% of these adult children have developed AD. The risk of AD in these children increases with age, being 31.0% (58 of 187) in those older than 60 years and 41.8% (41 of 98) in those older than 70 years. Many children (79.0%) at risk in these families are still younger than 70 years, meaning that the occurrence of AD will increase in the coming years. A family history of AD beyond the parents did not change the risk of AD in the children but did reduce the median age at onset in affected children. The apolipoprotein E epsilon 4 allele played an important part in this phenomenon but did not explain all cases of AD in the children. Conclusions: When both parents have AD, there is an increased risk of AD in their children beyond that of the general population. The role of family history and the specific genes involved in this phenomenon require a better definition. C1 [Schellenberg, Gerard D.; Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Jayadev, Suman; Steinbart, Ellen J.; Schellenberg, Gerard D.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Chi, Yueh-Yun; Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chi, Yueh-Yun; Kukull, Walter A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chi, Yueh-Yun] Univ Florida, Dept Epidemiol, Gainesville, FL USA. [Chi, Yueh-Yun] Univ Florida, Dept Hlth Policy Res, Gainesville, FL USA. RP Bird, TD (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu OI Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [AG17586, P50 AG 005136-22] NR 26 TC 23 Z9 24 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2008 VL 65 IS 3 BP 373 EP 378 DI 10.1001/archneurol.2007.61 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 272TD UT WOS:000253881900012 PM 18332250 ER PT J AU Mata, IF Samii, A Schneer, SH Roberts, JW Griffith, A Leis, BC Schellenberg, GD Sidransky, E Bird, TD Leverenz, JB Tsuang, D Zabetian, CP AF Mata, Ignacio F. Samii, Ali Schneer, Seth H. Roberts, John W. Griffith, Alida Leis, Berta C. Schellenberg, Gerard D. Sidransky, Ellen Bird, Thomas D. Leverenz, James B. Tsuang, Debby Zabetian, Cyrus P. TI Glucocerebrosidase gene mutations - A risk factor for Lewy body disorders SO ARCHIVES OF NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; GAUCHER-DISEASE; ASHKENAZI-JEWS; ASSOCIATION AB Background: Mutations in the glucocerebrosidase (GBA) gene have been reported to modify risk for Parkinson disease (PD) and dementia with Lewy bodies (DLB). However, these findings have not been consistently replicated, and most studies have had substantial methodological shortcomings. Objective: To better assess the role of GBA variants in altering risk for Lewy body disorders. Design: Case-control study. Setting: Four movement disorder clinics in the Seattle, Washington, area. Participants: Seven hundred twenty-one patients with PD, 554 healthy control subjects, and 57 patients with DLB. Main Outcome Measures: Disease status and presence or absence of the 2 most common GBA mutations (N370S and L444P). Results: We observed a significantly higher heterozygote frequency for the 2 mutations in patients with PD (2.9%; P<.001) and those with DLB (3.5%; P=.045) compared with control subjects (0.4%). Conclusion: Our findings suggest that GBA mutations exert a large effect on susceptibility for Lewy body disorders at the individual level but are associated with a modest (approximately 3%) population-attributable risk in individuals of European ancestry. C1 [Mata, Ignacio F.; Schellenberg, Gerard D.; Bird, Thomas D.; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Leverenz, James B.; Tsuang, Debby; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Samii, Ali; Leverenz, James B.; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Mata, Ignacio F.; Samii, Ali; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Schellenberg, Gerard D.; Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Schellenberg, Gerard D.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Leverenz, James B.; Tsuang, Debby] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Schneer, Seth H.] Oberlin Coll, Dept Biol, Oberlin, OH 44074 USA. [Griffith, Alida; Leis, Berta C.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [U01 AG016976]; NINDS NIH HHS [K08 NS044138-05, K08 NS044138] NR 20 TC 98 Z9 101 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2008 VL 65 IS 3 BP 379 EP 382 DI 10.1001/archneurol.2007.68 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 272TD UT WOS:000253881900013 PM 18332251 ER PT J AU Wiggs, JL AF Wiggs, Janey L. TI Association between LOXL1 and pseudoexfoliation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID GLAUCOMA; DEPOSITION; PROTEIN RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 13 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2008 VL 126 IS 3 BP 420 EP 421 DI 10.1001/archopht.126.3.420 PG 2 WC Ophthalmology SC Ophthalmology GA 272TE UT WOS:000253882000017 PM 18332326 ER PT J AU Wiggs, JL AF Wiggs, Janey L. TI Genomic promise - Personalized medicine for ophthalmology SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID MACULAR DEGENERATION; POLYMORPHISMS; GLAUCOMA; MODEL RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 18 TC 9 Z9 9 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2008 VL 126 IS 3 BP 422 EP 423 DI 10.1001/archopht.126.3.422 PG 2 WC Ophthalmology SC Ophthalmology GA 272TE UT WOS:000253882000018 PM 18332327 ER PT J AU Rapuano, BE Boursiquot, R Tomin, E MacDonald, DE Maddula, S Raghavan, D Lane, JM Helfet, DL AF Rapuano, Bruce E. Boursiquot, Roosevelt Tomin, Emre MacDonald, Daniel E. Maddula, Surekha Raghavan, Deepak Lane, Joseph M. Helfet, David L. TI The effects of COX-1 and COX-2 inhibitors on prostaglandin synthesis and the formation of heterotopic bone in a rat model SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE heterotopic; ossification; prostaglandins; cyclooxygenase-1; cyclooxygenase-2 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACETABULAR FRACTURE SURGERY; TOTAL HIP-ARTHROPLASTY; LOW-DOSE IRRADIATION; CYCLOOXYGENASE-2 INHIBITORS; MORPHOGENETIC PROTEIN-2; INDUCIBLE CYCLOOXYGENASE; RHEUMATOID-ARTHRITIS; ANIMAL-MODELS; OSSIFICATION AB Introduction Traumatic heterotopic ossification (HO) is a common clinical condition associated with various orthopedic procedures that involve injury to soft tissues near bone. In this study, we tested the hypothesis that the prophylactic effects of NSAID's in the treatment of HO are mediated via inhibition of the COX-2 enzyme. Here we describe a rat model that simulates HO in the human that was used to test the above hypothesis. Materials and methods Heterotopic ossification was surgically induced in the quadriceps by injury to the muscle and femoral periosteum and transplantation of donor bone marrow cells containing osteoprogenitors into the site of injury. HO was imaged and quantified by micro-CT scanning of femurs removed from sacrificed animals at 6 weeks post-injury, three-dimensional computer reconstructions of the scanned bones and computer-assisted morphometric analysis. Prostaglandin E-2 (PGE(2)) synthesis was quantified using an enzyme immunoassay system. The effects of a nonselective COX inhibitor or specific inhibitors of COX-1 or COX-2 following oral administration on the content of ectopic bone and PGE(2) were also measured. Results Micro-CT and histological analyses demonstrated that all of the femurs in operated limbs developed HO in the vastus lateralis muscle belly of the quadriceps close to the anterior femur. Only the COX-1,2 nonselective and COX-2 inhibitors significantly decreased HO formation (by about one-third in each case; P < 0.05). PGE(2) synthesis at the site of injury was increased 50- and 100-fold (to 25 ng/g tissue) within 1 and 7 days, respectively, post-injury with the levels declining to near baseline within 2 weeks of surgery. Both the COX-1,2 nonselective and COX-2 inhibitors significantly decreased PGE(2) levels to 25% of control HO levels within 24 h of the first administration, even at low dosages. The COX-1 inhibitor only produced the same effect after 1 week of administration. Conclusion These findings suggest that although inhibitors of COX-2 or COX-1 reduced PGE(2) synthesis, only the COX-2 enzyme plays a role in the mechanism of traumatic HO. C1 [Rapuano, Bruce E.; Tomin, Emre; MacDonald, Daniel E.; Lane, Joseph M.; Helfet, David L.] Hosp Special Surg, Div Res, New York, NY 10021 USA. [Boursiquot, Roosevelt] Mt Sinai Sch Med, New York, NY USA. [MacDonald, Daniel E.] Columbia Univ, New York, NY USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [Maddula, Surekha] SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. [Raghavan, Deepak] Univ Med & Dent New Jersey, New Brunswick, NJ USA. RP Rapuano, BE (reprint author), Hosp Special Surg, Div Res, 535 E 70th St, New York, NY 10021 USA. EM Rapuanob@hss.edu NR 64 TC 10 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0936-8051 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD MAR PY 2008 VL 128 IS 3 BP 333 EP 344 DI 10.1007/s00402-007-0436-2 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 259DD UT WOS:000252918400016 PM 18034350 ER PT J AU Sipp, JA Ashland, J Hartnick, CJ AF Sipp, J. Andrew Ashland, Jean Hartnick, Christopher J. TI Injection pharyngoplasty with calcium hydroxyapatite for treatment of velopalatal insufficiency SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID VELOPHARYNGEAL INSUFFICIENCY; WALL AUGMENTATION; RADIESSE; SURGERY; IMPLANT AB Objective: To evaluate the efficacy of injectable calcium hydroxylapatite for treatment of velopalatal (VP) insufficiency (VPI). Design: Observational case series of 7 patients treated with injectable calcium hydroxylapatite for VPI and followed for 10 to 24 months. Setting: Academic pediatric otolaryngology practice. Patients: Seven children aged 6 to 16 years with clinically significant VPI stemming from documented small VP gaps and who did not benefit from speech therapy were treated with calcium hydroxylapatite injection pharyngoplasty. Intervention: Posterior pharyngeal wall augmentation with calcium hydroxylapatite. Main Outcome Measures: Treatment success was defined as (1) speech improvement to the degree that parents felt no additional treatment was needed and (2) meeting postoperative nasometric measures. Treatment failure was defined as parental report of insufficient improvement in speech. Complications and additional treatments for VPI were noted. Results: There were no major complications in any of the 7 children injected with calcium hydroxylapatite. There was I minor complication: I patient was readmitted for postoperative pain and dehydration. Of the 7 patients, 4 experienced a satisfactory result for up to 17 months. Findings from postoperative nasometry were either within reference range, or less than I SD greater than the reference range, for all sounds. There were 3 treatment failures, each with preexisting craniofacial abnormality. Two patients in the group that failed treatment later underwent revision superior pharyngeal flap surgery without complication or hindrance from the calcium hydroxylapatite injection. Four children underwent subsequent magnetic resonance imaging evaluations up to I year after injection, which revealed no evidence of migration. Conclusions: The data from this small series suggest that posterior pharyngeal wall injection with calcium hydroxylapatite is safe and may be effective in treating select patients with VPI. Further longitudinal studies, with a larger series of patients, examining the safety, efficacy, and patient selection are warranted to better understand the possible use of posterior pharyngeal wall injection of calcium hydroxylapatite in children with symptomatic VPI. C1 [Sipp, J. Andrew; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Ashland, Jean] Massachusetts Gen Hosp, Dept Speech & Language Pathol, Boston, MA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Hartnick@meei.harvard.edu NR 15 TC 25 Z9 26 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAR PY 2008 VL 134 IS 3 BP 268 EP 271 DI 10.1001/archotol.134.3.268 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 272RU UT WOS:000253878200006 PM 18347251 ER PT J AU Steele, BG Belza, B Cain, KC Coppersmith, J Lakshminarayan, S Howard, J Haselkorn, JK AF Steele, Bonnie G. Belza, Basia Cain, Kevin C. Coppersmith, Jeff Lakshminarayan, Sambasiva Howard, JoEllen Haselkorn, Jodie K. TI A randomized clinical trial of an activity and exercise adherence intervention in chronic pulmonary disease SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE behavior therapy; exercise therapy; health status; patient compliance; quality of life; rehabilitation ID QUALITY-OF-LIFE; CHRONIC LUNG-DISEASE; PHYSICAL-ACTIVITY; OLDER-ADULTS; FUNCTIONAL STATUS; HOME REHABILITATION; ENERGY-EXPENDITURE; HEALTH-STATUS; SELF-REPORT; COPD AB Objectives: To evaluate the effectiveness of an exercise adherence intervention to maintain daily activity, adherence to exercise, and exercise capacity over 1 year after completion of an outpatient pulmonary rehabilitation program. Design: A 2-group, experimental design was used with randomization into intervention and usual care groups. Setting: Outpatient pulmonary rehabilitation program in a university-affiliated medical center. Participants: One hundred six subjects (98 men; 98 with chronic obstructive pulmonary disease) with a mean age of 67 years and chronic lung disease. Intervention: Twelve-week adherence intervention (weekly phone calls and home visit) including counseling on establishing, monitoring, and problem-solving in maintaining a home exercise program. Main Outcome Measures: Primary outcomes included daily activity (accelerometer), exercise adherence (exercise diary), and exercise capacity (six-minute walk test). All measures were performed at baseline, after the pulmonary rehabilitation program (8wk), after the adherence intervention (20wk), and at 1 year. Results: A rank-based analysis of covariance showed less decline at 20 weeks in exercise adherence (intervention mean, +3min: control mean, - 13min; P = .015) and exercise capacity (intervention mean. - 10.7m; control mean, -35.4m; P = .023). There were no differences in daily activity at 20 weeks or any differences in any primary variable at 1 year. Conclusions: The intervention enhanced exercise adherence and exercise capacity in the short term but produced no long-term benefit. These bindings are in part attributed to the disappointing measurement characteristics of the accelerometer used to measure daily activity. The intervention was acceptable to participants. Further study is needed to fashion interventions that have more persistent benefit. C1 [Steele, Bonnie G.; Lakshminarayan, Sambasiva] Puget Sound Hlth Care Syst, Dept Vet Affairs, Primary Care & Specialty Med Serv, Seattle, WA USA. [Belza, Basia; Cain, Kevin C.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Coppersmith, Jeff; Howard, JoEllen] VA Puget Sound Hlth Care Syst, VA Hlth Serv, Res & Dev, Seattle, WA USA. [Haselkorn, Jodie K.] Univ Washington, Dept Vet Affairs, Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Vet Affairs, Puget Sound Hlth Care Syst, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Vet Affairs, Puget Sound Hlth Care Syst, Dept Epidemiol, Seattle, WA 98195 USA. RP Steele, BG (reprint author), Puget Sound Med Ctr, S-111-B,1600 Columbian Way S, Seattle, WA 98108 USA. EM bonnie.steele@med.va.gov NR 50 TC 67 Z9 68 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2008 VL 89 IS 3 BP 404 EP 412 DI 10.1016/j.apmr.2007.11.003 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 273UU UT WOS:000253958100003 PM 18295615 ER PT J AU Kim, J Brienza, DM Lynch, RA Cooper, RA Boninger, ML AF Kim, Jongbae Brienza, David M. Lynch, Robert A. Cooper, Rory A. Boninger, Michael L. TI Effectiveness evaluation of a remote accessibility assessment system for wheelchair users using virtualized reality SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Conference of the Rehabilitation-Engineering-and-Assistive-Technology-Society-of-North-Ame rica CY JUN 22-26, 2006 CL Atlanta, GA SP Rehab Engn & Assistive Technol Soc N Amer DE disabled persons; imaging; three-dimensional; rehabilitation; wheelchairs ID TELEREHABILITATION AB Objective: To determine the value of the Remote Accessibility Assessment System (RAAS), a 3-dimensional (3D) image reconstruction technology designed to analyze accessibility of the target built environment in a virtualized reality, in assessing a built environment's accessibility by calculating the congruence level between the RAAS and conventional in-person method. Design: Repeated-measures (within-subject) design. Setting: A university research laboratory. Participants: Three homes for people who use wheeled mobility devices. Intervention: Home physical environment was divided into several potential problem areas such as entrance, hallway, bathroom, and living room. Each area was identified by several tasks that might be performed in it. All possible tasks in each area within each home were evaluated using 2 methods: RAAS and the conventional in-person assessment. The evaluations were performed by a different home modification specialist for each method. Main Outcome Measures: Conventional in-person assessments Were cross-tabulated with assessments from RAAS, with which there are 4 possible assessment combinations. A true positive (checked-checked) occurs when the RAAS method checks the target task as problematic and it is also checked as problematic by the conventional in-person method. True negative (not checked-not checked), false positive (not checked-checked), and false negative (checked-not checked) were also identified as the same way. Results: The proportion of overall agreement was high at 94.1% and the overall sensitivity and specificity was 95.6% and 90.3%. respectively. A significant K coefficient of 857 and the 95% confidence interval of the odds ratio of 104.062 to 404.921 were calculated and a high level of overall agreement rate was shown. A high P value (.868) of the McNemar test implied that there was no marginal homogeneity, that is, no tendency to identify the task incorrectly in the positive or negative direction. Conclusions: This system proved that virtualized reality and 3D reconstruction technology may provide an effective means to investigate the architectural features of a built environment without an expert visiting the site. This system could become an efficient tool for the service provider and can provide expert service to underserved clients that would otherwise be unavailable. C1 [Kim, Jongbae; Brienza, David M.; Cooper, Rory A.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Kim, Jongbae; Brienza, David M.; Cooper, Rory A.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, VA Ctr Excellence Wheelchairs & Assoc Rehabil Eng, Pittsburgh, PA 15206 USA. [Kim, Jongbae; Brienza, David M.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Lynch, Robert A.] Lynch & Assoc, Pittsburgh, PA USA. RP Kim, J (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 151R-1,7180 Highland Dr Bldg 4,2nd Fl E, Pittsburgh, PA 15206 USA. EM jbkim@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 25 TC 2 Z9 2 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2008 VL 89 IS 3 BP 470 EP 479 DI 10.1016/j.apmr.2007.08.158 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 273UU UT WOS:000253958100013 PM 18295625 ER PT J AU Gallagher, RM Rosenthal, LJ AF Gallagher, Rollin M. Rosenthal, Lisa J. TI Chronic pain and opiates: balancing pain control and risks in long-term opioid treatment SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE analgesics; opioids; pain; rehabilitation ID POSTHERPETIC NEURALGIA; NONMALIGNANT PAIN; NEUROPATHIC PAIN; CONTROLLED-TRIAL; PRIMARY-CARE; DOUBLE-BLIND; BACK-PAIN; MEDICINE; EFFICACY; POPULATION AB The risks and benefits of opioid analgesics for chronic pain conditions and diseases are discussed in the context of the concern about the public health problems of poorly managed pain and prescription drug abuse and addiction. New strategies for risk management in treating patients with chronic pain are described. Opioids for chronic pain may be used effectively in the context of clinical strategies for risk management and selectively tailored, biopsychosocial pain management. Overall Article Objective: To present the case for balanced use of opioid therapy in the treatment of chronic pain conditions. C1 [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Pain Serv, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.; Rosenthal, Lisa J.] Univ Penn, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Philadelphia VA Med Ctr, Pain Serv, Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM rgallagh@mail.med.upenn.edu NR 59 TC 26 Z9 26 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2008 VL 89 IS 3 SU 1 BP S77 EP S82 DI 10.1016/j.apmr.2007.12.003 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 276TX UT WOS:000254167100014 PM 18295655 ER PT J AU Sabatine, MS Ploughman, L Simonsen, KL Iakoubova, OA Kirchgessner, TG Ranade, K Tsuchihashi, Z Zerba, KE Long, DU Tong, CH Packard, CJ Pfeffer, MA Devlin, JJ Shepherd, J Campos, H Sacks, FM Braunwald, E AF Sabatine, Marc S. Ploughman, Lynn Simonsen, Katy L. Iakoubova, Olga A. Kirchgessner, Todd G. Ranade, Koustubh Tsuchihashi, Zenta Zerba, Kim E. Long, Diane U. Tong, Carmen H. Packard, Christopher J. Pfeffer, Marc A. Devlin, James J. Shepherd, James Campos, Hannia Sacks, Frank M. Braunwald, Eugene TI Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE genetics; coronary heart disease; matrix metalloproteinases; statins ID FACTOR PATHWAY INHIBITOR-2; ARTERY-DISEASE; ATHEROSCLEROSIS; INFLAMMATION; VERSICAN; TRIALS AB Objective-The purpose of this study was to investigate the association between the (Ala)227(Pro) polymorphism in the ADAMTS1 metalloproteinase gene and coronary heart disease and benefit from statin therapy in 2 independent cohorts. Methods and Results-The frequency of the ADAMTS1 227(Pro) minor allele was 0.24 in 2421 male subjects from CARE, a randomized trial of pravastatin versus placebo. In the placebo arm, homozygotes (6.3% of study population) had a significantly increased risk of fatal coronary disease or nonfatal myocardial infarction (D/MI) compared with noncarriers (OR 2.12, 95% CI 1.07 to 4.19, P=0.03), and in the entire study the benefit of pravastatin in reducing the risk of D/MI was greater in these subjects (OR 0.21, 95% CI 0.06 to 0.69) than in heterozygotes (OR 0.74, 95% CI 0.48 to 1.14) or noncarriers (OR 0.99, 95% CI 0.68 to 1.42; P-interaction = 0.044). Results were tested in 1565 male subjects from WOSCOPS, also a randomized trial of pravastatin versus placebo. Similar to the results in CARE, in the placebo arm subjects homozygous for the minor allele were at increased risk of D/MI (OR 1.72, P=0.052) and in the entire study the benefit of pravastatin in reducing D/MI was greater in these subjects (OR 0.24, 95% CI 0.09 to 0.68) than in heterozygotes (OR 0.73, 95% CI 0.48 to 1.11) or noncarriers (OR 0.65, 95% CI 0.20 to 2.09) (P-interaction=0.029). Conclusions-In men not on pravastatin, those homozygous for the 227Pro allele of ADAMTS1 have a nearly 2-fold increased risk of coronary heart disease events compared with noncarriers. In this high-risk group, treatment with pravastatin is highly efficacious, reducing the odds of fatal coronary disease or nonfatal MI by approximately 75%, as compared with 25% in noncarriers or heterozygotes. C1 [Sabatine, Marc S.; Pfeffer, Marc A.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. [Ploughman, Lynn; Simonsen, Katy L.; Kirchgessner, Todd G.; Ranade, Koustubh; Tsuchihashi, Zenta; Zerba, Kim E.] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA. [Simonsen, Katy L.] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. [Iakoubova, Olga A.; Long, Diane U.; Tong, Carmen H.; Devlin, James J.] Celera, Alameda, CA USA. [Campos, Hannia; Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Packard, Christopher J.; Shepherd, James] Univ Glasgow, Glasgow, Lanark, Scotland. [Packard, Christopher J.; Shepherd, James] Royal Infirm, Glasgow G31 2ER, Lanark, Scotland. RP Sabatine, MS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. EM mssabatine@partners.org RI Simonsen, Katy/A-4193-2012 FU NHLBI NIH HHS [R01 HL072879] NR 21 TC 30 Z9 34 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2008 VL 28 IS 3 BP 562 EP 567 DI 10.1161/ATVBAHA.107.156653 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 266IZ UT WOS:000253429000033 PM 18174457 ER PT J AU Bamberg, F Dannemann, N Shapiro, MD Seneviratne, SK Ferencik, M Butler, J Koenig, W Nasir, K Cury, RC Tawakol, A Achenbach, S Brady, TJ Hoffmann, U AF Bamberg, Fabian Dannemann, Nina Shapiro, Michael D. Seneviratne, Sujith K. Ferencik, Maros Butler, Javed Koenig, Wolfgang Nasir, Khurram Cury, Ricardo C. Tawakol, Ahmed Achenbach, Stephan Brady, Thomas J. Hoffmann, Udo TI Association between cardiovascular risk profiles and the presence and extent of different types of coronary atherosclerotic plaque as detected by multidetector computed tomography SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE tomography; atherosclerosis; imaging ID AMERICAN-HEART-ASSOCIATION; INTRAVASCULAR ULTRASOUND; DISEASE; LESIONS; COMMITTEE; COUNCIL; CALCIUM; CULPRIT; ADULTS; MEN AB Objective-To assess the association between cardiovascular risk factors and extent of noncalcified-(NCAP), mixed( MCAP), and calcified coronary atherosclerotic plaque (CAP). Methods and Results-In this cross-sectional study, we included consecutive subjects who presented with chest pain but had no history of coronary artery disease (CAD) and did not develop acute coronary syndrome. Contrast-enhanced 64-slice coronary MDCT was performed to determine the presence of NCAP, MCAP, and CAP for each coronary segment. Among 195 patients (91 women, mean age: 54.6 +/- 12.0) exclusively NCAP was detected in 11 patients (5.6%). The extent of NCAP decreased and the extent of MCAP and CAP increased with age (P=0.06, P=0.02, and P=0.13, respectively). Hyperlipidemia and family history of CAD were associated with the extent of NCAP after adjusting for other risk factors (P=0.02 and P=0.04, respectively) or for the extent of MCAP and CAP (P=0.02 and P=0.05, respectively). Conclusions-Our data suggest that only a small proportion of individuals have exclusively NCAP and indicate that the relation of NCAP and CAP changes with age. Among individual risk factors, hyperlipidemia and family history of CAD may be associated with the extent of NCAP. Larger observational trials are necessary to confirm our findings. C1 [Bamberg, Fabian; Dannemann, Nina; Shapiro, Michael D.; Seneviratne, Sujith K.; Ferencik, Maros; Butler, Javed; Nasir, Khurram; Cury, Ricardo C.; Tawakol, Ahmed; Achenbach, Stephan; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Dannemann, Nina; Shapiro, Michael D.; Seneviratne, Sujith K.; Ferencik, Maros; Butler, Javed; Nasir, Khurram; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Koenig, Wolfgang] Univ Ulm, Dept Cardiol, D-89069 Ulm, Germany. [Achenbach, Stephan] Univ Erlangen Nurnberg, Dept Cardiol, Erlangen, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Charles River Plaza Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU NHLBI NIH HHS [R01 HL080053] NR 19 TC 63 Z9 65 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2008 VL 28 IS 3 BP 568 EP 574 DI 10.1161/ATVBAHA.107.155010 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 266IZ UT WOS:000253429000034 PM 18174458 ER PT J AU Chu, A Ahn, H Halwan, B Kalmin, B Artifon, ELA Barkun, A Lagoudakis, MG Kumar, A AF Chu, Adrienne Ahn, Hongshik Halwan, Bhawna Kalmin, Bruce Artifon, Everson L. A. Barkun, Alan Lagoudakis, Michail G. Kumar, Atul TI A decision support system to facilitate management of patients with acute gastrointestinal bleeding SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE class prediction; cross validation; gastrointestinal bleeding; machine learning ID ARTIFICIAL NEURAL-NETWORK; CLINICAL GUIDELINE; HOSPITAL LENGTH; HEMORRHAGE; RISK; PREDICTORS; MORTALITY; DIAGNOSIS; ENDOSCOPY; MODELS AB Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved. C1 [Kumar, Atul] SUNY Stony Brook, US Dept Vet Affairs, Stony Brook, NY 11794 USA. [Chu, Adrienne; Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Halwan, Bhawna] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Kalmin, Bruce] Med Univ S Carolina, Div Gastroenterol, Charleston, SC 29425 USA. [Artifon, Everson L. A.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Barkun, Alan] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Lagoudakis, Michail G.] Tech Univ Crete, Intelligent Syst Lab, Dept Elect & Comp Engn, Kounoupidiana 73100, Chania Hellas, Greece. RP Kumar, A (reprint author), SUNY Stony Brook, US Dept Vet Affairs, Stony Brook, NY 11794 USA. EM atul.kumar2@va.gov RI Lagoudakis, Michail/C-5145-2008 NR 41 TC 28 Z9 28 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD MAR PY 2008 VL 42 IS 3 BP 247 EP 259 DI 10.1016/j.artmed.2007.10.003 PG 13 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 279UD UT WOS:000254379400006 PM 18063351 ER PT J AU Maemura, T Shin, M Kinoshita, M Majima, T Ishihara, M Saitoh, D Ichikura, T AF Maemura, Tomoyuki Shin, Michael Kinoshita, Manabu Majima, Takashi Ishihara, Masayuki Saitoh, Daizoh Ichikura, Takashi TI A tissue-engineered stomach shows presence of proton pump and G-cells in a rat model, resulting in improved anemia following total gastrectomy SO ARTIFICIAL ORGANS LA English DT Article DE yissue-engineered stomach; total gastrectomy; pernicious anemia ID QUALITY-OF-LIFE; JEJUNAL POUCH; GASTRIC-CANCER; RECONSTRUCTION AB Despite advances in surgical reconstruction, total gastrectomy still is accompanied by various complications, especially chronic ones, such as pernicious anemia, resulting in refractory malnutrition. As an alternative approach, we have proposed a tissue-engineered stomach as a replacement of the native stomach. This study aimed to assess the secretory functions of a tissue-engineered stomach in a rat model and the nutritional status of the recipients over an extended time period. Stomach epithelial organoid units were isolated from neonatal rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of adult recipient rats. After 3 weeks, cyst-like structures had formed, henceforth referred to as tissue-engineered stomachs. The recipient stomachs were resected and replaced by their tissue-engineered counterparts. At 24 weeks after implantation, the secretory function of the tissue-engineered stomach was evaluated using immunohistochemical staining. The hemoglobin levels and nutritional status of the recipients were compared with a control group that had undergone a simple Roux-en-Y reconstruction following total gastrectomy. Recipient rats tolerated the tissue-engineered stomachs well. X-ray examination using barium as contrast showed no bowel stenosis. Staining for proton pump alpha-subunit and gastrin demonstrated the existence of parietal cells and G-cells in the neogastric mucosa, respectively, suggesting secretory functions. The treatment group showed significantly higher hemoglobin levels than the control group, although no differences in the body weight change, total protein, or cholesterol levels were observed between the two groups. A tissue-engineered stomach has the potential to function as a food reservoir following total gastrectomy. It is conjectured that replacement with a tissue-engineered stomach might restore the proton pump parietal cells and G-cells, and thereby improve anemia after a total gastrectomy in a rat model. C1 [Maemura, Tomoyuki; Kinoshita, Manabu; Saitoh, Daizoh] Natl Def Med Coll, Res Inst, Div Traumatol, Tokorozawa, Saitama 3598513, Japan. [Maemura, Tomoyuki; Majima, Takashi; Ichikura, Takashi] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 3598513, Japan. [Shin, Michael] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shin, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ishihara, Masayuki] Natl Def Med Coll, Res Inst, Div Biomed Engn, Tokorozawa, Saitama 3598513, Japan. RP Maemura, T (reprint author), Natl Def Med Coll, Res Inst, Div Traumatol, Namiki 3-2, Tokorozawa, Saitama 3598513, Japan. EM manabu@ndmc.ac.jp NR 11 TC 8 Z9 8 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD MAR PY 2008 VL 32 IS 3 BP 234 EP 239 DI 10.1111/j.1525-1594.2007.00528.x PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 268UN UT WOS:000253605300010 PM 18201286 ER PT J AU Schmid, M Pflederer, T Jang, IK Ropers, D Sei, K Daniel, WG Achenbach, S AF Schmid, Michael Pflederer, Tobias Jang, Ik-Kyung Ropers, Dieter Sei, Komatsu Daniel, Werner G. Achenbach, Stephan TI Relationship between degree of remodeling and CT attenuation of plaque in coronary atherosclerotic lesions: An in-vivo analysis by multi-detector computed tomography SO ATHEROSCLEROSIS LA English DT Article DE multi-detector computed tomography; coronary atherosclerotic plaque; remodeling; plaque attenuation; coronary arteries; vulnerable plaque ID INTRAVASCULAR ULTRASOUND; COMPENSATORY ENLARGEMENT; ARTERY-DISEASE; NONINVASIVE ASSESSMENT; STABLE ANGINA; ROW CT; CLINICAL PRESENTATION; HELICAL CT; ANGIOGRAPHY; MORPHOLOGY AB Multi-detector CT (MDCT) permits non-invasive visualization of the coronary arteries. Coronary plaque can be visualized, and earlier studies have indicated that the CT attenuation measured in atherosclerotic plaques is influenced by plaque composition. Also, MDCT has been shown to permit assessment of remodeling of coronary atherosclerotic lesions. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion. We thus evaluated the relationship between remodeling and CT attenuation of coronary atherosclerotic plaque by MDCT. Methods: Seventy-six patients were investigated by contrast-enhanced 64-slice CT. One-hundred twelve atherosclerotic lesions without substantial calcification and visualized with high image quality were selected. Multiplanar reconstructions orthogonal to the coronary artery were rendered at the lesion and the proximal reference site. Cross-sectional vessel areas were measured to determine the remodeling index (RI: lesion vessel area/reference vessel area) and the CT attenuation of plaque was measured by fitting a region of interest to the plaque area. CT attenuation of plaque was correlated to the presence of positive remodeling index (RI > 1.05). Results: The mean cross-sectional vessel area in the lesion was 0.25 +/- 0.08 cm(2), the mean reference vessel area was 0.22 +/- 0.09 cm(2). The mean CT attenuation of the atherosclerotic plaque in the lesions was 71 26 HU. CT attenuation of plaque was significantly lower in 72 lesions that displayed positive remodeling (59 +/- 22 HU) than in 40 lesions with no or with negative remodeling (91 +/- 20 HU, p < 0.001). Conclusions: Positive remodeling of coronary atherosclerotic lesions correlates to lower CT attenuation of plaque, which has been demonstrated to be associated with lipid-rich plaque. Both characteristics indicate increased risk for plaque rupture and subsequent events and could thus prove useful when the use of CT imaging for the detection of "vulnerable plaque" is considered. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Schmid, Michael; Pflederer, Tobias; Ropers, Dieter; Sei, Komatsu; Daniel, Werner G.; Achenbach, Stephan] Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, Erlangen, Germany. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schmid, M (reprint author), Univ Klinikum Erlangen, Med Klin Kardiol 2, Ulmenweg 18, D-91504 Erlangen, Germany. EM Schmid1208@gmx.de NR 48 TC 50 Z9 52 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 2008 VL 197 IS 1 BP 457 EP 464 DI 10.1016/j.atherosclerosis.2007.07.003 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 282LS UT WOS:000254569900063 PM 17727859 ER PT J AU Nahrendorf, M Sosnovik, DE Weissleder, R AF Nahrendorf, Matthias Sosnovik, David E. Weissleder, Ralph TI MR-optical imaging of cardiovascular molecular targets SO BASIC RESEARCH IN CARDIOLOGY LA English DT Review DE atherosclerosis; molecular imaging; fluorescence; MRI ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; CELL-ADHESION MOLECULE-1; MACROPHAGES IN-VIVO; OXIDE-ENHANCED MRI; ATHEROSCLEROTIC PLAQUES; IRON-OXIDE; HYPERLIPIDEMIC RABBITS; E-SELECTIN; NANOPARTICLES; INFLAMMATION AB Our understanding of the intricate inflammation biology underlying atherosclerosis is rapidly progressing. Molecular imaging strategies, harnessing this body of knowledge, have been developed to visualize some key cellular and molecular events in plaque evolution and vulnerability. Here, we discuss recent advances in magnetic resonance and fluorescence imaging of key biomarkers including adhesion molecules, inflammatory cells, and enzyme activity. We discuss strengths and limitations of respective imaging technologies, and comment on the potential of multi-modality imaging approaches. C1 [Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL078641-03, R01-HL078641, R01 HL078641, U01 HL080731-03, U01 HL080731, K08 HL079984, U01-HL080731] NR 46 TC 20 Z9 20 U1 1 U2 4 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAR PY 2008 VL 103 IS 2 BP 87 EP 94 DI 10.1007/s00395-008-0707-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 270YO UT WOS:000253756300003 PM 18324364 ER PT J AU Sosnovik, DE Nahrendorf, M Weissleder, R AF Sosnovik, David E. Nahrendorf, Matthias Weissleder, Ralph TI Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications SO BASIC RESEARCH IN CARDIOLOGY LA English DT Review DE molecular; imaging; MRI; nanoparticles; iron oxide; cardiovascular ID SUPERPARAMAGNETIC IRON-OXIDE; MESENCHYMAL STEM-CELLS; IN-VIVO; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL INFARCT; CONTRAST AGENT; PARTICLES; CANCER; ACCUMULATION; ANGIOGENESIS AB Magnetic nanoparticles (MNP) are playing an increasingly important role in cardiovascular molecular imaging. These agents are superparamagnetic and consist of a central core of iron-oxide surrounded by a carbohydrate or polymer coat. The size, physical properties and pharmacokinetics of MNP make them highly suited to cellular and molecular imaging of atherosclerotic plaque and myocardial injury. MNP have a sensitivity in the nanomolar range and can be detected with T1, T2, T2*, off resonance and steady state free precession sequences. Targeted imaging with MNP is being actively explored and can be achieved through either surface modification or through the attachment of an affinity ligand to the nanoparticle. First generation MNP are already in clinical use and second generation agents, with longer blood half lives, are likely to be approved for routine clinical use in the near future. C1 [Sosnovik, David E.; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU NCI NIH HHS [P01CA117969-015904, R24 CA092782, R24-CA92782]; NHLBI NIH HHS [T32 HL007864, K08 HL079984, K08 HL079984-03, R01HL07864, U01 HL080731, U01HL080731]; NIBIB NIH HHS [R01 EB004626, R01EB004626] NR 46 TC 133 Z9 139 U1 4 U2 47 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAR PY 2008 VL 103 IS 2 BP 122 EP 130 DI 10.1007/s00395-008-0710-7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 270YO UT WOS:000253756300007 PM 18324368 ER PT J AU Clarke, SB Rizvi, SL Resick, PA AF Clarke, Stephanie B. Rizvi, Shireen L. Resick, Patricia A. TI Borderline personality characteristics and treatment outcome in cognitive-behavioral treatments for PTSD in female rape victims SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL-ABUSE; CHILDHOOD; THERAPY; WOMEN; COMORBIDITY; DEPRESSION; IMPAIRMENT; DIAGNOSES; INVENTORY AB Many studies report that comorbid borderline personality pathology is associated with poorer outcomes in the treatment of Axis I disorders. Given the high rates of comorbidity between borderline personality pathology and posttraumatic stress disorder (PTSD), it is essential to determine whether borderline symptomatology affects PTSD treatment outcome. This study examined the effects of borderline personality characteristics (BPC) on 131 female rape victims receiving cognitive-behavioral treatment for PTSD. Higher BPC scores were associated with greater pretreatment PTSD severity; however, individuals with higher levels of BPC were just as likely to complete treatment and also as likely to show significant treatment response on several outcome measures. There were no significant interactions between type of treatment and BPC on the outcome variables. Findings suggest that women with borderline pathology may be able to benefit significantly from cognitive-behavioral treatment for PTSD. C1 [Rizvi, Shireen L.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Rizvi, Shireen L.; Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Rizvi, SL (reprint author), New Sch Social Res, 65 5th Ave,Room 334, New York, NY 10003 USA. EM RizviS@newschool.edu FU NIMH NIH HHS [R01 MH051509, R01 MH051509-10] NR 33 TC 33 Z9 33 U1 3 U2 10 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2008 VL 39 IS 1 BP 72 EP 78 DI 10.1016/j.beth.2007.05.002 PG 7 WC Psychology, Clinical SC Psychology GA 323BM UT WOS:000257419000008 PM 18328872 ER PT J AU Flessner, CA Conelea, CA Woods, DW Franklin, ME Keuthen, NJ Cashin, SE AF Flessner, Christopher A. Conelea, Christine A. Woods, Douglas W. Franklin, Martin E. Keuthen, Nancy J. Cashin, Susan E. TI Styles of pulling in trichotillomania: Exploring differences in symptom severity, phenomenology, and functional impact SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE focused; automatic; pulling; trichotillomania ID MGH HAIRPULLING SCALE; EXPERIENTIAL AVOIDANCE; PSYCHOMETRIC PROPERTIES; HABIT-REVERSAL; NERVOUS HABITS; DEPRESSION AB Previous research has examined possible phenomenological differences between "focused" (i.e., with a compulsive quality) and "automatic" (i.e., with decreased awareness) pulling associated with trichotillomania (TTM), but these constructs have not been assessed using psychometrically sound measures. In the current study, differences in TTM severity, phenomenology, comorbid psychiatric symptoms, and functional impact were examined across individuals with varying combinations of "focused" and "automatic" pulling styles. Participants aged 18 and older were recruited via an internet-based survey. Those meeting inclusion criteria and completing the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A; n = 1545) were classified as either high- or low-focused and either high- or low-automatic based on scores obtained from the focused and automatic scales of the MIST-A using a median split procedure. Results showed some significant differences between pulling styles. For example, "high-automatic" pullers reported more severe TTM and greater stress than "low-automatic" pullers, and "high-focused" pullers reported more severe TTM, greater stress and depression, and greater functional impact than "low-focused" pullers. Subsequent analyses suggest that, in comparison to individuals experiencing low levels of both automatic and focused pulling, those experiencing high levels of each pulling style reported greater severity, psychological impact, and functional impact. Clinical and research implications, study limitations, and future areas of research are discussed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Flessner, Christopher A.; Conelea, Christine A.; Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53211 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cashin, Susan E.] Univ Wisconsin, Dept Human Movement Sci, Milwaukee, WI 53201 USA. RP Woods, DW (reprint author), Univ Wisconsin, Dept Psychol, POB 413, Milwaukee, WI 53211 USA. EM dwoods@uwm.edu RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; OI Conelea, Christine/0000-0003-2791-9802 NR 27 TC 54 Z9 54 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD MAR PY 2008 VL 46 IS 3 BP 345 EP 357 DI 10.1016/j.brat.2007.12.009 PG 13 WC Psychology, Clinical SC Psychology GA 285NV UT WOS:000254784400005 PM 18249363 ER PT J AU Tam, WF Gilliland, G AF Tam, Winnie F. Gilliland, Gary TI Can FLT3 inhibitors overcome resistance in AML? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article; Proceedings Paper CT 12th Acute Leukemia Forum CY MAR 23, 2007 CL San Francisco, CA DE FLT3 inhibitors; resistance; staurosporine; midostaurin; PKC412; tandutinib; MLN 518; lestaurtinib; CEP701; SU11248; AML ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; INTERNAL TANDEM DUPLICATION; ADULT PATIENTS; IN-VITRO; CHEMOTHERAPY; PKC412; MUTATIONS; MLN518; INDUCTION AB The identification of FLT3 mutations across a range of the cytogenetic subgroups of AML has opened up the possibility of a targeted therapeutic approach with broad applicability. Four agents are currently in clinical trials, at least 3 of which have both sufficient activity against AML and sufficiently acceptable toxicity profiles to support continued efforts to refine their inclusion into therapeutic regimens for AML. Better understanding of the genetics of inherent and acquired resistance is needed to guide development of second-generation agents. Optimizing the integration of FLT3 inhibitor therapy with chemotherapy has the potential both to decrease toxicity and improve response. C1 [Gilliland, Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, 1 Blackfan Circle,Room 5-0210, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu FU Howard Hughes Medical Institute NR 24 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2008 VL 21 IS 1 BP 13 EP 20 DI 10.1016/j.beha.2007.11.003 PG 8 WC Hematology SC Hematology GA 284ZX UT WOS:000254748200003 PM 18342808 ER PT J AU Bowie, CR Leung, WW Reichenberg, A McClure, MM Patterson, TL Heaton, RK Harvey, PD AF Bowie, Christopher R. Leung, Winnie W. Reichenberg, Abraham McClure, Margaret M. Patterson, Thomas L. Heaton, Robert K. Harvey, Philip D. TI Predicting schizophrenia patients' real-world behavior with specific neuropsychological and functional capacity measures SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cognition; disability; functional outcome; neuropsychology; schizophrenia ID NEUROCOGNITIVE DEFICITS; CLINICAL SYMPTOMS; SOCIAL COGNITION; OLDER PATIENTS; MENTALLY-ILL; PERFORMANCE; SKILLS; OUTPATIENTS; OUTCOMES; TASKS AB Background: Significant neuropsychological (NP) and functional deficits are found in most schizophrenia patients. Previous studies have left questions as to whether global NP impairment or discrete domains affect functional outcomes, and none have addressed distinctions within and between ability and performance domains. This study examined the different predictive relationships between NP domains, functional competence, social competence, symptoms, and real-world behavior in domains of work skills, interpersonal relationships, and community activities. Methods: Two hundred twenty-two schizophrenic outpatients were tested with an NP battery and performance-based measures of functional and social competence and rated for positive, negative, and depressive symptoms. Case managers generated ratings of three functional disability domains. Results: Four cognitive factors were derived from factor analysis. Path analyses revealed both direct and mediated effects of NP on real-world outcomes. All NP domains predicted functional competence, but only processing speed and attention/working memory predicted social competence. Both competence measures mediated the effects of NP on community activities and work skills, but only social competence predicted interpersonal behaviors. The attention/working memory domain was directly related to work skills, executive functions had a direct effect on interpersonal behaviors, and processing speed had direct effects on all three real-world behaviors. Symptoms were directly related to outcomes, with fewer relationships with competence. Conclusions: Differential predictors of functional competence and performance were found from discrete NP domains. Separating competence and performance provides a more precise perspective on correlates of disability. Changes in specific NP or functional skills might improve specific outcomes, rather than promoting global functional improvement. C1 [Bowie, Christopher R.; Leung, Winnie W.; Reichenberg, Abraham; McClure, Margaret M.; Harvey, Philip D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Bowie, Christopher R.; Leung, Winnie W.; McClure, Margaret M.] James J Peters Bronx Vet Affairs Med Ctr, Bronx, NY USA. [Leung, Winnie W.; McClure, Margaret M.] Univ Calif San Diego, Educ Clin Ctr, Vet Affairs Vet Integrat Serv Network 3 Mental Il, San Diego, CA USA. [Patterson, Thomas L.; Heaton, Robert K.] Univ Calif San Diego, San Diego Med Ctr, Dept Psychiat, San Diego, CA USA. RP Bowie, CR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,4th Floor,Box 1230, New York, NY 10029 USA. EM christopher.bowie@mssm.edu FU NIMH NIH HHS [R01 MH063116-05, MH 36692, MH 63116, R01 MH063116, R01 MH078737, R01 MH078775] NR 40 TC 270 Z9 275 U1 5 U2 19 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 MAR 1 PY 2008 VL 63 IS 5 BP 505 EP 511 DI 10.1016/j.biopsych.2007.05.022 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263ZZ UT WOS:000253256300010 PM 17662256 ER PT J AU Ballen, KK Barker, JN Stewart, SK Greene, MF Lane, TA AF Ballen, Karen K. Barker, Juliet N. Stewart, Susan K. Greene, Michael F. Lane, Thomas A. TI Collection and preservation of cord blood for personal use SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE cord blood; personal storage ID BONE-MARROW; UNRELATED DONORS; ACUTE-LEUKEMIA; STEM-CELLS; TRANSPLANTATION; ADULTS; OUTCOMES; BANKING; THALASSEMIA; DISEASE AB Unrelated-donor umbilical cord blood (CB) is a useful alternative hematopoietic stem cell source for patients without suitably matched and readily available related or unrelated stem cell donors. Expectant parents today may have the option of either donating the CB to a public CB bank or keeping and storing the CB in a private bank for potential use in the future. The alternatives are often referred to as public banking and private banking. On behalf of the American Society of Blood and Marrow Transplantation (ASBMT), we have reviewed the currently available data and opinions and offer the following recommendations: 1. Public donation of CB is encouraged where possible. 2. The probability of using one's own CB is very small-difficult to quantify but probably as low as 0.04% (1:2500) to 0.0005% (1:200,000) in the first 20 years of life-and therefore, storage of CB for personal use is not recommended. 3. Family member banking (collecting and storing CB for a family member) is recommended when there is a sibling with a disease that may be treated successfully with allogeneic transplant. Family member banking on behalf of a parent with a disease that may be treated successfully with allogeneic transplant is only recommended when there are shared HLA-antigens between the parents. The committee acknowledges the expanding potential of indications for CB in the future, and suggests review of these recommendations at regular intervals. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Ballen, Karen K.; Greene, Michael F.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Barker, Juliet N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Stewart, Susan K.] BMT InfoNet, Highland Pk, IL USA. [Lane, Thomas A.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson Pl,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org NR 36 TC 60 Z9 62 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2008 VL 14 IS 3 BP 356 EP 363 DI 10.1016/j.bbmt.2007.11.005 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 265FC UT WOS:000253343500013 PM 18275904 ER PT J AU Kim, S Kim, SS Lee, SH Ahn, SE Gwak, SJ Song, JH Kim, BS Chung, HM AF Kim, Sinae Kim, Sang-Soo Lee, Soo-Hong Ahn, Seong Eun Gwak, So-Jung Song, Joon-Ho Kim, Byung-Soo Chung, Hyung-Min TI In vivo bone formation from human embryonic stem cell-derived osteogenic cells in poly(D,L-lactic-co-glycolic acid)/hydroxyapatite composite scaffolds SO BIOMATERIALS LA English DT Article DE human embryonic stem cells; osteogenic differentiation; scaffold; bone regeneration; BMP-2; tissue engineering ID DIFFERENTIATION; VITRO; CULTURE; GROWTH AB We have previously reported the efficient osteogenic differentiation of human embryonic stem cells (hESCs) by co-culture with primary human bone-derived cells (hPBDs) without the use of exogenous factors. In the present study, we explored whether osteogenic cells derived from hESCs (OC-hESCs) using the previously reported method would be capable of regenerating bone tissue in vivo. A three-dimensional porous poly(D,L-lactic-co-glycolic acid)/hydroxyapatite composite scaffold was used as a cell delivery vehicle. In vivo implantation of OC-hESC-seeded scaffolds showed significant bone formation in the subcutaneous sites of immunodeficient mice at 4 and 8 weeks after implantation (n = 5 for each time point). Meanwhile, implantation of the control no cell-seeded scaffolds or human dermal fibroblast-seeded scaffolds did not show any new bone formation. In addition, the presence of BMP-2 (1 mu g/scaffold) enhanced new bone tissue formation in terms of mineralization and the expression of bone-specific genetic markers. According to FISH analysis, implanted OC-hESCs remained in the regeneration sites, which suggested that the implanted cells participated in the formation of new bone. In conclusion, OC-hESCs successfully regenerated bone tissue upon in vivo implantation, and this regeneration can be further enhanced by the administration of BMP-2. These results suggest the clinical feasibility of OC-hESCs as a good alternative source of cells for bone regeneration. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Kim, Sinae; Lee, Soo-Hong; Ahn, Seong Eun; Chung, Hyung-Min] Pochan CHA Univ, Grad Sch Life Sci, CHA Stem Cell Inst, Seoul 135081, South Korea. [Kim, Sang-Soo; Kim, Byung-Soo] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. [Kim, Sang-Soo] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. [Gwak, So-Jung] Hanyang Univ, Dept Chem Engn, Seoul 133791, South Korea. [Song, Joon-Ho] Hallym Univ, Cared Heart Hosp, Dept Neurosurg, Kyonggi Do, South Korea. RP Chung, HM (reprint author), Pochan CHA Univ, Grad Sch Life Sci, CHA Stem Cell Inst, 606-16 Yoeksam 1-Dong, Seoul 135081, South Korea. EM bskim@hanyang.ac.kr; safe33msh@gmail.com RI kim, sang-soo/C-6573-2009; Kim, Byung-Soo/O-2352-2013 NR 25 TC 98 Z9 104 U1 0 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR PY 2008 VL 29 IS 8 BP 1043 EP 1053 DI 10.1016/j.biomaterials.2007.11.005 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 260MM UT WOS:000253014400009 PM 18023477 ER PT J AU Salvatore, P Ghidini, S Zita, G De Panfilis, C Lambertino, S Maggini, C Baldessarini, RJ AF Salvatore, Paola Ghidini, Stefano Zita, Gianmaria De Panfilis, Chiara Lambertino, Samuele Maggini, Carlo Baldessarini, Ross J. TI Circadian activity rhythm abnormalities in ill and recovered bipolar I disorder patients SO BIPOLAR DISORDERS LA English DT Article DE acrophase; actigraphy; bipolar disorder; depression; mania; mixed state; phase advance; trait marker ID SEASONAL AFFECTIVE-DISORDER; REST-ACTIVITY DISTURBANCES; DEPRESSED-PATIENTS; MOTOR-ACTIVITY; PSYCHOMOTOR ACTIVITY; MANIC-DEPRESSIVES; AFFECTIVE-ILLNESS; PHASE-ADVANCE; WRIST ACTIVITY; SLEEP AB Objectives: Most physiological indicators of bipolar disorder (BPD) reflect current acute illness, and rarely have proved to be state-independent. Activity rhythms are highly abnormal in acute phases of BPD; we compared circadian activity rhythms in BPD I patients during ill and recovered states to those of normal controls to test the hypothesis that some abnormalities may persist. Methods: We compared 36 adult DSM-IV BPD I patients during acute mania or mixed states, and during full and sustained clinical recovery, to 32 healthy controls of similar age and sex distribution, using wrist-worn, piezoelectric actigraphic monitoring for 72 h and computed cosinor analysis of circadian activity rhythms. Results: We verified expected major differences between manic or mixed-state BPD I patients and matched normal controls, including phase advances averaging 2.1 h in ill BPD I patients and 1.8 h in recovered patients. Moreover, recovered BPD patients differed highly significantly from controls in several measures, including acrophase advance, higher percentage of nocturnal sleep, and lower average daily activity (mesor). Actigraphic measures among recovered BPD patients were independent of ratings of mania (on the Young Mania Rating Scale), depression (on the Hamilton Depression Rating Scale), or rating-scale scored subjective distress, as well as the type and dose of concurrent psychotropic medication. Conclusions: These findings suggest that abnormal activity rhythms, including sustained phase advances, may represent enduring (trait) characteristics of BPD patients even during clinical recovery. If verified, such indices may be useful in supporting diagnoses and as an objective phenotype for genetic or other biological studies. C1 [Salvatore, Paola; Baldessarini, Ross J.] McLean Div Massachusetts Gen Hosp, Mailman Res Ctr, Int Consort Bipolar Disorder Res, Schizophrenia & Bipolar Disorder Program, Belmont, MA USA. [Salvatore, Paola; De Panfilis, Chiara; Maggini, Carlo] Univ Parma, Inst Psychiat, Dept Neurosci, Parma, Italy. [Ghidini, Stefano; Zita, Gianmaria; Lambertino, Samuele; Maggini, Carlo] Univ Parma, Sch Psychiat, Parma, Italy. RP Salvatore, P (reprint author), McLean Hosp, Int Consort Bipolar Disorder Res, Ctr Bldg GO7B,115 Mill St, Belmont, MA 02478 USA. EM psalvatore@mclean.harvard.edu NR 97 TC 64 Z9 65 U1 8 U2 22 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2008 VL 10 IS 2 BP 256 EP 265 DI 10.1111/j.1399-5618.2007.00505.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 260AN UT WOS:000252982300004 PM 18271904 ER PT J AU Matthews, AM Huckans, MS Blackwell, AD Hauser, P AF Matthews, Annette M. Huckans, Marilyn S. Blackwell, Aaron D. Hauser, Peter TI Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; comorbidity; epidemiology; hepatitis C; interferon; mental health; mood disorders; substance use disorders; United States Department of Veterans Affairs ID UNITED-STATES; VIRUS-INFECTION; PREVALENCE; ILLNESS; VETERANS AB Objectives: To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group. Methods: Data were retrospectively collected on 325,410 patients seen between 1998 and 2004 within facilities and clinics of the Veterans Integrated Service Network (VISN) 20 Northwest Veterans Health Care Administration from electronic medical records. HCV screening and prevalence rates were compared between the BD, SUD, DD, and control groups. Odds ratios and relative risks were determined and compared between groups. Results: Patients in the BD, SUD, and DD groups had been tested at a higher rate than controls and were at increased risk for HCV infection compared with controls. These high-risk groups had a 1.31-fold, 4.86-fold, and 5.46-fold increase in the relative risk of HCV infection, respectively. Overall, compared to the control group, the relative risk of a patient having HCV if he or she had BD (with or without an SUD) was 3.6. Conclusions: Patients with BD and comorbid SUD had an over fourfold increase in relative risk for HCV than our control group and a similar risk as patients in our SUD group. Furthermore, even if bipolar patients did not have a comorbid SUD (the BD group), their relative risk of HCV was significantly higher than that of the control group. This suggests that patients with BD, particularly those with a comorbid SUD, should be screened and tested for HCV. C1 [Matthews, Annette M.; Huckans, Marilyn S.; Hauser, Peter] Oregon Hlth & Sci Univ, NW Hepatatis C Resource Ctr, Portland, OR USA. [Matthews, Annette M.; Huckans, Marilyn S.; Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Matthews, Annette M.; Huckans, Marilyn S.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. [Blackwell, Aaron D.] Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Jens Lab, Portland, OR USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Div Gastroenterol, Portland, OR USA. RP Matthews, AM (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,PO Box 1035 V3MHC, Portland, OR 97202 USA. EM annette.matthews@med.va.gov; peter.hauser2@med.va.gov RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 26 TC 20 Z9 20 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2008 VL 10 IS 2 BP 266 EP 270 DI 10.1111/j.1399-5618.2007.00472.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 260AN UT WOS:000252982300005 PM 18271905 ER PT J AU Misra, S Socherman, R Park, BS Hauser, P Ganzini, L AF Misra, Sahana Socherman, Robert Park, Byung S. Hauser, Peter Ganzini, Linda TI Influence of mood state on capacity to consent to research in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; clinical trials; decision-making capacity ID INFORMED-CONSENT; MENTAL-ILLNESS; SCHIZOPHRENIA; COMPETENCE; PARTICIPATION; ISSUES AB Objectives: Experts have debated the ability of patients with bipolar illness to consent to research participation when manic. We compared 25 euthymic bipolar and 26 manic bipolar patients in their understanding of three hypothetical studies of varying complexity. Methods: Hypothetical studies were presented as written informed consent forms, which were reread up to three times. Questions included assessment of hypothetical study purposes, procedures, risks and benefits, and voluntariness of participation. Results: After adjusting for educational level, subjects with mania had lower mean understanding scores for all three hypothetical studies compared to euthymic subjects on initial assessment. By the end of Trial 3 of each hypothetical study, there were no significant differences between groups. The proportion of subjects with mania who met predetermined pass criteria for sufficient understanding was lower than the proportion of euthymic subjects on initial assessment of the first hypothetical study, but not the other hypothetical studies (odds ratio = 0.24; 95% confidence interval = 0.07 - 0.8; p = 0.02). Both groups exhibited an increase in the pass proportion by the end of the third trial for each hypothetical study with no significant differences between groups. Conclusions: We conclude that subjects with mania exhibited significantly poorer levels of understanding of relevant information in hypothetical research consent forms compared to euthymic subjects when initially presented with research information. The improvement in manic patients' understanding scores with the iterative review of consent forms suggests that many manic patients may be able to consent to research protocols containing an educational intervention as a part of the informed consent process. C1 [Misra, Sahana; Socherman, Robert; Hauser, Peter; Ganzini, Linda] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR USA. [Misra, Sahana; Socherman, Robert] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. [Park, Byung S.] Oregon Hlth & Sci Univ, OHSU Canc Inst, Bioinformat & Biostat Shared Resource, Portland, OR USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Mood Disorders Res & Treatment Ctr, Portland, OR USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat Behav Neurosci & Med, Portland, OR USA. [Ganzini, Linda] Oregon Hlth & Sci Univ, Comorbid Mental & Phys Disorders, Columbia Ctr Stud Chronic, Portland, OR USA. [Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Psychiat & Med, Portland, OR USA. RP Misra, S (reprint author), Portland VAMC P3MHDC, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM misras@ohsu.edu OI /0000-0003-3516-7516 NR 16 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2008 VL 10 IS 2 BP 303 EP 309 DI 10.1111/j.1399-5618.2007.00525.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 260AN UT WOS:000252982300010 PM 18271910 ER PT J AU Sadetsky, N Lubeck, DP Pasta, DJ Latini, DM DuChane, J Carroll, PR AF Sadetsky, Natalia Lubeck, Deborah P. Pasta, David J. Latini, David M. DuChane, Janeen Carroll, Peter R. TI Insurance and quality of life in men with prostate cancer: data from the Cancer of the Prostate Strategic Urological Research Endeavor SO BJU INTERNATIONAL LA English DT Article DE insurance status; quality of life; prostatic neoplasms ID HEALTH-INSURANCE; RADICAL PROSTATECTOMY; SOCIOECONOMIC-STATUS; LOW-INCOME; COVERAGE; CARCINOMA; RISK; MORTALITY; VETERANS; OUTCOMES AB OBJECTIVE To evaluate the effect of medical insurance coverage on health-related quality of life (HRQoL) outcomes in men newly diagnosed with prostate cancer, as insurance status has been shown to be related to clinical presentation, and types of treatments received for localized prostate cancer, but the relationship of insurance and QoL has not been explored sufficiently. PATIENTS AND METHODS Data from the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE), a national longitudinal database registry of men with prostate cancer, were used for this study. Men who were newly diagnosed at entry to CaPSURE and completed one questionnaire before treatment, and one or more afterwards, were included. Insurance groups specific to age distribution of the study population were assessed, i.e. Medicare, preferred provider organizations (PPOs), health maintenance organizations (HMOs), fee for service (FFS), and the Veterans Administration (VA) for the younger group, and Medicare only, Medicare plus supplement (+S), and HMO/PPO for the older group. Associations between patients' clinical and sociodemographic characteristics and insurance status were evaluated by chi-square and analysis of variance. Relationships between insurance status and HRQoL outcomes over time were evaluated by multivariate mixed model. RESULTS Of 2258 men who met the study criteria, 1259 were younger and 999 were older than 65 years. More than half of the younger patients belonged to an HMO or PPO (42.2% and 32.5%, respectively), with the remainder distributed between Medicare, FFS and VA. In the older group most men belonged to Medicare only and the Medicare +S groups (22.4% and 58.8%, respectively). There was greater variation in clinical risk categories at presentation by insurance groups in the younger group. In the multivariate analysis, insurance status was significantly associated with changes in most HRQoL outcomes over time in the younger group, while in the older patients the effect of insurance diminished. Men in the VA and Medicare systems had lower scores at baseline and a steeper decline in Physical Function, Role Physical, Role Emotional, Social Function, Bodily Pain, Vitality, and General Health domains over time, controlling for type of initial treatment received, timing of HRQoL assessment, number of comorbidities, clinical risk at presentation, and income. CONCLUSION Insurance was independently related to changes in a wide range of HRQoL outcomes in men aged < 65 years treated for prostate cancer. With the latest advances in early diagnosis and treatment of prostate cancer, clinicians and researchers should be aware of the specific groups of patients who are more vulnerable to the adverse effects of treatment and subsequent decline in functioning. The present findings could provide important tools for understanding the process of recovery after treatment for prostate cancer, and identifying needs for specific services. C1 [Sadetsky, Natalia; Lubeck, Deborah P.; Pasta, David J.; Carroll, Peter R.] Univ Calif San Francisco, Ctr Comprehens Canc, Urol Outcomes Res Grp, Program Urol Oncol,Dept Urol, San Francisco, CA 94143 USA. [Latini, David M.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [DuChane, Janeen] TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Sadetsky, N (reprint author), Box 0738,1600 Divisadero St,Suite B642, San Francisco, CA 94115 USA. EM nsadetsky@urology.ucsf.edu OI Latini, David/0000-0002-6161-4861; Pasta, David/0000-0003-2637-9293 FU PHS HHS [P50 C89520] NR 34 TC 8 Z9 8 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2008 VL 101 IS 6 BP 691 EP 697 DI 10.1111/j.1464-410X.2007.07353.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 263YA UT WOS:000253251200007 PM 18291018 ER PT J AU Choueiri, TK Baz, RC McFadden, CM Khasawneh, M Karam, MA Kelly, M Hussein, MA AF Choueiri, Toni K. Baz, Rachid C. McFadden, Carolyn M. Khasawneh, Mohamad Karam, Mary Ann Kelly, Megan Hussein, Mohamad A. TI An association between renal cell carcinoma and multiple myeloma: a case series and clinical implications SO BJU INTERNATIONAL LA English DT Article DE multiple myeloma; renal cell carcinoma; renal mass; expected incidence ID TUMOR-SUPPRESSOR GENE; CANCER; SURVIVAL; THERAPY AB Objective To describe an association between renal cell carcinoma (RCC) and multiple myeloma (MM) in patients with both disorders, and suggest possible explanations for the association. Patients and Method We retrospectively reviewed the records of patients with MM and RCC at the Cleveland Clinic between 1990 and 2005, and identified 1100 with MM, 2704 with RCC and eight with concomitant MM and RCC. The medical records of these eight patients were reviewed. Results In four of the eight patients, RCC was diagnosed after the MM at 3, 8, 23 and 46 months, respectively; in the remaining four, the RCC was diagnosed before MM by 108, 35, 13 and 1 months, respectively. The number of cases of RCC expected in the present 1100 patients with MM over 15 years was lower than the four recorded (P < 0.001, Fisher's exact test). Similarly, the number of cases of MM expected in the 2704 patients with RCC was also lower than the four recorded (P < 0.001, Fisher's exact test). Conclusions RCC and MM can occur in the same patient at an incidence higher than the expected rate. Possible explanations include genetic abnormalities, environmental exposures or immune-related mechanisms predisposing to the second malignancy. These findings are particularly relevant in the management of patients with known RCC and lytic bone lesions, or those with known MM and subsequent or concomitant renal masses, especially those involving the right kidney. C1 [Hussein, Mohamad A.] H Lee Moffitt Canc & Res Inst, Div Hematol Malignancies, Tampa, FL 33612 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Baz, Rachid C.; McFadden, Carolyn M.; Khasawneh, Mohamad; Karam, Mary Ann; Kelly, Megan] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. RP Hussein, MA (reprint author), H Lee Moffitt Canc & Res Inst, Div Hematol Malignancies, 12902 Magnolis Dr,SRB-4, Tampa, FL 33612 USA. EM mohamad.hussein@moffitt.org NR 9 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2008 VL 101 IS 6 BP 712 EP 715 DI 10.1111/j.1464-410X.2007.07268.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 263YA UT WOS:000253251200013 PM 17970789 ER PT J AU Neto, BS Smith, GL Mandeville, JA Vanni, AJ Wotkowicz, C Rieger-Christ, KM Baumgart, E Jacobs, MA Cohen, MS Zeheb, R Loda, M Libertino, JA Summerhayes, IC AF Neto, Brasil Silva Smith, Gjanje L. Mandeville, Jessica A. Vanni, Alex J. Wotkowicz, Chad Rieger-Christ, Kimberly M. Baumgart, Egbert Jacobs, Micah A. Cohen, Michael S. Zeheb, Ron Loda, Massimo Libertino, John A. Summerhayes, Ian C. TI Prognostic significance of altered p120(ctn) expression in bladder cancer SO BJU INTERNATIONAL LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; P120 CATENIN; E-CADHERIN; ABNORMAL EXPRESSION; CARCINOMA CELLS; COLON-CARCINOMA; BETA-CATENIN; P120-CATENIN; LOCALIZATION; ADHESION AB To identify the frequency of change in the expression and localization of p120(ctn) in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120(ctn) in the migratory and invasive behaviour of bladder carcinoma cells. In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2-T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120(ctn) immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120(ctn) was achieved using small-interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays. The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non-membranous localization of p120(ctn) correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN-positive disease (P = 0.02). A low expression level of p120(ctn) was linked to a poor outcome in cancer-specific survival analysis. Knockdown of p120(ctn) using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells. Our findings suggest that p120(ctn) acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells. C1 [Neto, Brasil Silva; Rieger-Christ, Kimberly M.; Summerhayes, Ian C.] Lahey Clin Fdn, Cell & Mol Biol Lab, Robert E Wise MD Res & Educ Inst, Burlington, MA 01805 USA. [Zeheb, Ron] Lahey Clin Fdn, Dept Pathol, Burlington, MA 01805 USA. [Smith, Gjanje L.; Mandeville, Jessica A.; Vanni, Alex J.; Wotkowicz, Chad; Rieger-Christ, Kimberly M.; Baumgart, Egbert; Jacobs, Micah A.; Cohen, Michael S.; Libertino, John A.; Summerhayes, Ian C.] Lahey Clin Fdn, Dept Urol, Burlington, MA USA. [Loda, Massimo] Dana Farber Canc Ctr Inst, Dept Pathol, Boston, MA USA. [Loda, Massimo] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Summerhayes, IC (reprint author), Lahey Clin Fdn, Cell & Mol Biol Lab, Robert E Wise MD Res & Educ Inst, 31 Mall Rd, Burlington, MA 01805 USA. EM ian.c.summerhayes@lahey.org NR 32 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2008 VL 101 IS 6 BP 746 EP 752 DI 10.1111/j.1464-410X.2007.07264.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 263YA UT WOS:000253251200020 ER PT J AU Raponi, M Lancet, JE Fan, HT Dossey, L Lee, G Gojo, I Feldman, EJ Gotlib, J Morris, LE Greenberg, PL Wright, JJ Harousseau, JL Lowenberg, B Stone, RM De Porre, P Wang, YX Karp, JE AF Raponi, Mitch Lancet, Jeffrey E. Fan, Hongtao Dossey, Lesley Lee, Grace Gojo, Ivana Feldman, Eric J. Gotlib, Jason Morris, Lawrence E. Greenberg, Peter L. Wright, John J. Harousseau, Jean-Luc Loewenberg, Bob Stone, Richard M. De Porre, Peter Wang, Yixin Karp, Judith E. TI A 2-gene classifier for predicting response to the famesyltransferase inhibitor tipifarnib in acute myeloid leukemia SO BLOOD LA English DT Article ID ACUTE-MYELOGENOUS-LEUKEMIA; B-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; NUCLEOTIDE EXCHANGE FACTOR; BREAST-CANCER; TRANSFERASE INHIBITORS; ACTIVATING MUTATIONS; COLORECTAL-CANCER; LUNG-CANCER; IN-VITRO AB At present, there is no method available to predict response to farnesyltransferase inhibitors (FTIs). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1/APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy using a "leave one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair. The utility of this classifier for predicting response to tipifarnib was validated in an independent set of 58 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (1154 vs 56 days; P < .001), which was independent of other covariates, including a previously described prognostic gene expression classifier. Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib. C1 [Raponi, Mitch; Dossey, Lesley; Lee, Grace; Wang, Yixin] Veridex, La Jolla, CA USA. [Lancet, Jeffrey E.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Fan, Hongtao] Centocor R&D, Malvern, PA USA. [Gojo, Ivana] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Feldman, Eric J.] Cornell Univ, Weill Med Coll, New York, NY USA. [Gotlib, Jason; Greenberg, Peter L.] Stanford Canc Ctr, Stanford, CA USA. [Morris, Lawrence E.] Blood & Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Harousseau, Jean-Luc] CHU, Hotel Dieu, Serv Hematol Clin, Nantes, France. [Loewenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [De Porre, Peter] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Karp, Judith E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Raponi, M (reprint author), Johnson & Johnson Co, Veridex LLC, 3210 Merryfield Row, San Diego, CA 92121 USA. EM mraponi1@ocdus.jnj.com FU NCRR NIH HHS [M01 RR000052] NR 55 TC 73 Z9 74 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 MAR 1 PY 2008 VL 111 IS 5 BP 2589 EP 2596 DI 10.1182/blood-2007-09-112730 PG 8 WC Hematology SC Hematology GA 269SX UT WOS:000253671600023 PM 18160667 ER PT J AU Pardanani, A Fridley, BL Lasho, TL Gilliland, DG Tefferi, A AF Pardanani, Animesh Fridley, Brooke L. Lasho, Terra L. Gilliland, D. Gary Tefferi, Ayalew TI Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders SO BLOOD LA English DT Article ID JAK2 MUTATION; POLYCYTHEMIA-VERA; ASSOCIATION; JAK2V617F; EXPRESSION; HAPLOTYPE; RECEPTOR; HEMATOPOIESIS; TRAITS; TESTS AB JAK2V617F is an acquired mutation associated with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We tested the hypothesis that the paradox of a single disease allele associated with 3 distinctive clinical phenotypes could be explained in part by host-modifying influences. We screened for genetic variation within 4 candidate genes involved in JAK-STAT signaling, including receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had PV, 58 had PMF, and 37 had ET. Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, and rs-110974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF. Finally, intragene haplotypes in JAK2 were significantly associated with PV only. Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele. C1 [Pardanani, Animesh; Lasho, Terra L.; Tefferi, Ayalew] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Pardanani, Animesh; Lasho, Terra L.; Tefferi, Ayalew] Mayo Clin, Div Biostat, Rochester, MN 55905 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gilliland, D. Gary] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Pardanani, A (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM pardanani.animesh@mayo.edu RI Fridley, Brooke/D-8315-2015 OI Fridley, Brooke/0000-0001-7739-7956 NR 24 TC 83 Z9 90 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 MAR 1 PY 2008 VL 111 IS 5 BP 2785 EP 2789 DI 10.1182/blood-2007-06-095703 PG 5 WC Hematology SC Hematology GA 269SX UT WOS:000253671600046 PM 18006699 ER PT J AU Braun, SE Wong, FE Connole, M Taube, R Murakami, A Lisziewicz, J Marasco, WA Johnson, RP AF Braun, Stephen E. Wong, Fay Eng Connole, Michelle Taube, Ran Murakami, Akikazu Lisziewicz, Julianna Marasco, Wayne A. Johnson, R. Paul TI Initial evaluation of oncoretroviral vectors carrying HIV-1 inhibitor gene into rhesus CD34+cells and/or CD4+T cells: An in vivo model for the gene therapy of AIDS SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Braun, Stephen E.; Wong, Fay Eng; Connole, Michelle; Johnson, R. Paul] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. [Taube, Ran; Murakami, Akikazu; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Lisziewicz, Julianna] Res Inst Genet & Human Therpy, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 14 BP 257 EP 257 DI 10.1016/j.bcmd.2007.10.024 PG 1 WC Hematology SC Hematology GA 266YP UT WOS:000253474400033 ER PT J AU Buhlmann, U Reese, HE Renaud, S Wilhelm, S AF Buhlmann, Ulrike Reese, Hannah E. Renaud, Stefanie Wilhelm, Sabine TI Clinical considerations for the treatment of body dysmorphic disorder with cognitive-behavioral therapy SO BODY IMAGE LA English DT Review DE body dysmorphic disorder; cognitive behavior therapy; body image; depression; delusionality; motivation to change; personality; substance abuse ID OBSESSIVE-COMPULSIVE DISORDER; SUBSTANCE-USE DISORDERS; OVERVALUED IDEAS SCALE; OPEN-LABEL; IMAGINED UGLINESS; SPECTRUM DISORDER; ANOREXIA-NERVOSA; FOLLOW-UP; PREVALENCE; DYSMORPHOPHOBIA AB Although cognitive behavior therapy has been found to be very effective in the treatment of body dysmorphic disorder (BDD), there still remain a number of challenges that clinicians face in the treatment of individuals with BDD. In this article, we discuss issues related to comorbid depression, suicidality, substance use disorders, personality disorders as well as the role of early life experiences, delusional intensity of beliefs, and motivation to change. The aim of this review is to provide a treatment aid to clinicians by offering specific recommendations for improved care based on the available literature as well as our clinical experience. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Buhlmann, Ulrike; Renaud, Stefanie; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Body Dysmorph Disorder Clin, Boston, MA 02114 USA. [Reese, Hannah E.] Harvard Univ, Cambridge, MA 02138 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Body Dysmorph Disorder Clin, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 84 TC 14 Z9 14 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD MAR PY 2008 VL 5 IS 1 BP 39 EP 49 DI 10.1016/j.bodyim.2007.12.002 PG 11 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 320NN UT WOS:000257241900005 PM 18313372 ER PT J AU Maes, C Kobayashi, T Selig, MK Roth, SI Kronenberg, HM AF Maes, Christa Kobayashi, Tatsuya Selig, Martin K. Roth, Sanford I. Kronenberg, Henry M. TI Stage-specific subsets of perichondrial osteoblasts differentially relate to endothelium and bone and display different destinations in development SO BONE LA English DT Meeting Abstract CT International-Bone-and-Mineral-Society Davos Workshop on Bone Biology and Therapeutics CY MAR 09-14, 2008 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc, Alliance Better Bone Hlth, Amgen, F Hoffman La Roche LTD, Hologic Inc, Novartis Oncol, Merck, Pfizer C1 [Maes, Christa; Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Cambridge, MA 02138 USA. [Selig, Martin K.; Roth, Sanford I.] Massachusetts Gen Hosp, Dept Pathol, 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 8756-3282 J9 BONE JI Bone PD MAR PY 2008 VL 42 SU 1 MA 21 BP S25 EP S26 DI 10.1016/j.bone.2007.12.031 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271OX UT WOS:000253799600021 ER PT J AU Pozzi, S Hideshima, T Vallet, S Mukherjee, S Chhetri, S Cirstea, D Vaghela, N Thomas, C Rosa, D Rosen, E Ikeda, H Okawa, Y Breitkreutz, I Kiziltepe, T Santo, L Schoonmaker, J Schipani, E Bouxsein, ML Anderson, KC Raje, NS AF Pozzi, Samantha Hideshima, Teru Vallet, Sonia Mukherjee, Siddhartha Chhetri, Shweta Cirstea, Diana Vaghela, Nileshwari Thomas, Clare Rosa, Dilani Rosen, Eyal Ikeda, Hiroshi Okawa, Yutaka Breitkreutz, Iris Kiziltepe, Tanyel Santo, Loredana Schoonmaker, Jesse Schipani, Emestina Bouxsein, Mary L. Anderson, Kenneth C. Raje, Noopur S. TI High dose of Zoledronic acid inhibits both osteoclasts and osteoblasts in an in vivo mouse model SO BONE LA English DT Meeting Abstract CT International-Bone-and-Mineral-Society Davos Workshop on Bone Biology and Therapeutics CY MAR 09-14, 2008 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc, Alliance Better Bone Hlth, Amgen, F Hoffman La Roche LTD, Hologic Inc, Novartis Oncol, Merck, Pfizer C1 [Pozzi, Samantha; Hideshima, Teru; Vallet, Sonia; Chhetri, Shweta; Cirstea, Diana; Vaghela, Nileshwari; Ikeda, Hiroshi; Okawa, Yutaka; Breitkreutz, Iris; Kiziltepe, Tanyel; Santo, Loredana; Anderson, Kenneth C.; Raje, Noopur S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Adult O, Boston, MA 02115 USA. [Vallet, Sonia; Mukherjee, Siddhartha; Vaghela, Nileshwari; Thomas, Clare; Rosa, Dilani; Schoonmaker, Jesse; Schipani, Emestina; Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosen, Eyal; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Div Orthopaed Biomech Lab, Boston, MA 02215 USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAR PY 2008 VL 42 SU 1 MA 102 BP S63 EP S63 DI 10.1016/j.bone.2007.12.112 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271OX UT WOS:000253799600102 ER PT J AU Walkley, CR Qudsi, R Sankaran, VG Gostissa, M Roth, SI Rodda, SJ Snay, E Dunning, P Fahey, FH Alt, FW McMahon, AP Orkin, SH AF Walkley, Carl R. Qudsi, Rarneez Sankaran, Vijay G. Gostissa, Monica Roth, Stanford I. Rodda, Stephen J. Snay, Erin Dunning, Patricia Fahey, Frederic H. Alt, Frederick W. McMahon, Andrew P. Orkin, Stuart H. TI Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of rb, mimics the human disease SO BONE LA English DT Meeting Abstract CT International-Bone-and-Mineral-Society Davos Workshop on Bone Biology and Therapeutics CY MAR 09-14, 2008 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc, Alliance Better Bone Hlth, Amgen, F Hoffman La Roche LTD, Hologic Inc, Novartis Oncol, Merck, Pfizer C1 [Walkley, Carl R.; Qudsi, Rarneez; Sankaran, Vijay G.; Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. [Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. [Roth, Stanford I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, England. [Dunning, Patricia] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Orkin, Stuart H.] Brigham & Womens Hosp, Howard Hughes Med Inst, 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 8756-3282 J9 BONE JI Bone PD MAR PY 2008 VL 42 SU 1 MA 202 BP S109 EP S109 DI 10.1016/j.bone.2007.12.212 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271OX UT WOS:000253799600202 ER PT J AU Haspel, RL Kao, G Yeap, BY Cutler, C Soiffer, RJ Alyea, EP Ho, VT Koreth, J Dey, BR McAfee, SL Attar, EC Spitzer, T Antin, JH Ballen, KK AF Haspel, R. L. Kao, G. Yeap, B. Y. Cutler, C. Soiffer, R. J. Alyea, E. P. Ho, V. T. Koreth, J. Dey, B. R. McAfee, S. L. Attar, E. C. Spitzer, T. Antin, J. H. Ballen, K. K. TI Preinfusion variables predict the predominant unit in the setting of reduced-intensity double cord blood transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE double cord blood transplant; chimerism; engraftment ID HEMATOPOIETIC STEM-CELL; UNRELATED BONE-MARROW; ACUTE-LEUKEMIA; ADULTS; OUTCOMES; ENGRAFTMENT; CHILDREN; DONORS; NICHES; RISK AB Double cord blood transplantation (DCBT) may overcome the slow hematopoietic recovery and engraftment failure associated with infusion of a single cord blood unit. In DCBT, only one unit typically contributes to long-term hematopoiesis, but little is known about factors affecting cord predominance. As results from a phase I trial suggested that order of infusion may affect cord predominance, we analyzed the effect of preinfusion variables on chimerism patterns of 38 patients enrolled in the initial study and a subsequent phase II trial. All patients were treated with a reduced-intensity conditioning (RIC) regimen of fludarabine, melphalan and thymoglo-bulin followed by DCBT. By day 100, 66% of patients had hematopoiesis derived from a single cord blood unit. Higher post-thaw total nucleated cell and CD34+ cell dose were associated with cord predominance and in 68% of patients (P=0.03); the predominant cord blood unit was infused first. Only the post-thaw CD34+ cell dose of the predominant unit predicted time to both neutrophil and platelet engraftment. Although based on a small number of patients, our results identify parameters that may affect cord predominance and engraftment in the setting of DCBT following RIC and suggest possible strategies for selecting infusion order for cord blood units. C1 [Haspel, R. L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Kao, G.; Cutler, C.; Soiffer, R. J.; Alyea, E. P.; Ho, V. T.; Koreth, J.; Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Yeap, B. Y.; Dey, B. R.; McAfee, S. L.; Attar, E. C.; Spitzer, T.; Ballen, K. K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Haspel, RL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 300 Brookline Ave,Yamins 309, Boston, MA 02215 USA. EM rhaspel@bidmc.harvard.edu FU NCI NIH HHS [P01 CA142106-06A1, P01 CA142106]; NHLBI NIH HHS [P01 HL070149] NR 22 TC 33 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 IS 6 BP 523 EP 529 DI 10.1038/sj.bmt.1705933 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279DL UT WOS:000254335100003 PM 18037942 ER PT J AU Coppell, JA Richardson, PG Martin, PL Iacobelli, M Carreras, E Ruutu, T Barbui, T Soiffer, R Niederwieser, D AF Coppell, J. A. Richardson, P. G. Martin, P. L. Iacobelli, M. Carreras, E. Ruutu, T. Barbui, T. Soiffer, R. Niederwieser, D. TI Incidence of hepatic veno-occlusive disease following stem cell transplantation: systematic review of literature from 1979-2007 SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Coppell, J. A.] Imperial Coll Healthcare NHS Trust, London, England. [Richardson, P. G.; Soiffer, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, P. L.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Iacobelli, M.] Gentium SpA, Villa Guardia, Italy. [Carreras, E.] Hosp Clin Barcelona, Barcelona, Spain. [Ruutu, T.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Barbui, T.] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Niederwieser, D.] Univ Leipzig, Leipzig, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S91 EP S91 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200230 ER PT J AU Cutler, C Yeap, B Kao, G Ho, V Alyea, E Koreth, J Armand, P Dey, B Spitzer, T Soiffer, R Antin, J Ballen, K AF Cutler, C. Yeap, B. Kao, G. Ho, V. Alyea, E. Koreth, J. Armand, P. Dey, B. Spitzer, T. Soiffer, R. Antin, J. Ballen, K. TI Double umbilical cord blood transplantation using reduced-intensity conditioning: a single-centre experience SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Cutler, C.; Kao, G.; Ho, V.; Alyea, E.; Koreth, J.; Armand, P.; Soiffer, R.; Antin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yeap, B.; Dey, B.; Spitzer, T.; Ballen, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S23 EP S23 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200058 ER PT J AU Cutler, C Stevenson, K Kim, H Richardson, P Ho, V Revta, C Ebert, R Warren, D Koreth, J Armand, P Alyea, E Soiffer, R Antin, J AF Cutler, C. Stevenson, K. Kim, H. Richardson, P. Ho, V. Revta, C. Ebert, R. Warren, D. Koreth, J. Armand, P. Alyea, E. Soiffer, R. Antin, J. TI Sirolimus is associated with veno-occlusive disease of the liver after myeloablative transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Cutler, C.; Stevenson, K.; Kim, H.; Richardson, P.; Ho, V.; Revta, C.; Ebert, R.; Warren, D.; Koreth, J.; Armand, P.; Alyea, E.; Soiffer, R.; Antin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S7 EP S7 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200019 ER PT J AU Ho, V Dranoff, G Kim, H Vanneman, M Cutler, C Alyea, E Koreth, J Antin, J Ritz, J Soiffer, R AF Ho, V. Dranoff, G. Kim, H. Vanneman, M. Cutler, C. Alyea, E. Koreth, J. Antin, J. Ritz, J. Soiffer, R. TI GM-CSF secreting leukaemia cell vaccinations after allogeneic reduced-intensity peripheral blood stem cell transplantation for advanced myeloid malignancies SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Ho, V.; Dranoff, G.; Kim, H.; Vanneman, M.; Cutler, C.; Alyea, E.; Koreth, J.; Antin, J.; Ritz, J.; Soiffer, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. 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 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S408 EP S408 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359201032 ER PT J AU Lu, XS Lu, X Wang, ZCG Iglehart, JD Zhang, XG Richardson, AL AF Lu, Xuesong Lu, Xin Wang, Zhigang C. Iglehart, J. Dirk Zhang, Xuegong Richardson, Andrea L. TI Predicting features of breast cancer with gene expression patterns SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; computational molecular biology; gene expression profiling; metastasis ID LYMPH-NODE METASTASIS; OLIGONUCLEOTIDE ARRAYS; OVARIAN-CANCER; TUMOR; CLASSIFICATION; PROFILES; BIOLOGY; CARCINOMAS; SUBCLASSES; CHRONOLOGY AB Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate. C1 [Lu, Xin; Zhang, Xuegong; Richardson, Andrea L.] Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China. [Lu, Xuesong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lu, Xin] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Wang, Zhigang C.; Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wang, Zhigang C.; Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Zhang, XG (reprint author), Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China. EM lxs97@mails.tsinghua.edu.cn; zhangxg@tsinghua.edu.cn; arichardson@partners.org FU NCI NIH HHS [CA23100-22] NR 42 TC 115 Z9 118 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2008 VL 108 IS 2 BP 191 EP 201 DI 10.1007/s10549-007-9596-6 PG 11 WC Oncology SC Oncology GA 267QO UT WOS:000253524500005 PM 18297396 ER PT J AU Waldman, KL AF Waldman, Karen L. TI Treating victims of mass disaster and terrorism SO BULLETIN OF THE MENNINGER CLINIC LA English DT Book Review C1 [Waldman, Karen L.] Michael E Debakey Vet Affairs Med Ctr, Mental Hlth Care Line CMHP 116, Houston, TX 77030 USA. RP Waldman, KL (reprint author), Michael E Debakey Vet Affairs Med Ctr, Mental Hlth Care Line CMHP 116, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM waldman.Karen@med.va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SPR PY 2008 VL 72 IS 2 BP 149 EP 149 PG 1 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 330UR UT WOS:000257968800004 ER PT J AU Yabroff, KR Harlan, LC Clegg, LX Ballard-Barbash, R Stevens, J Weaver, DL AF Yabroff, K. Robin Harlan, Linda C. Clegg, Limin X. Ballard-Barbash, Rachel Stevens, Jennifer Weaver, Donald L. TI Is mode of breast cancer detection associated with cancer treatment in the united states? SO CANCER LA English DT Article DE mammography; breast cancer detection; breast cancer/detection; tamoxifen; chemotherapy; practice guidelines ID RANDOMIZED-TRIALS; ADJUVANT THERAPY; OLDER WOMEN; MAMMOGRAPHY; SURVIVAL; PATTERNS; PREDICTORS; RECURRENCE; TAMOXIFEN; INTERVAL AB BACKGROUND. The prognosis for women who have breast cancer detected by mammography is more favorable than that for women who have breast cancer detected by other methods, even after controlling for tumor characteristics. In the current study, the authors explored whether detection by mammography was associated with greater use of guideline-consistent breast cancer treatment among patients with recently diagnosed breast cancer in the United States. METHODS. The authors evaluated the association between mode of breast cancer detection (mammography vs other) and use of guideline-consistent treatment in 1006 women aged >= 40 years who were diagnosed in 2000. These patients were sampled from the Surveillance, Epidemiology, and End Results Program as part of the Patterns of Care studies. The analyses controlled for the potential confounders of clinical, demographic, and health system characteristics in multivariate logistic regression models. RESULTS. Breast cancer patients who were diagnosed by mammography were more likely to be aged >= 55 years, to have lower stage disease, and to be treated in larger hospitals than patients who were diagnosed by other methods (P <.05). Women whose breast cancer was diagnosed by a method other than mammography were more likely to receive guideline-consistent treatment than women who were diagnosed by mammography in unadjusted (odds ratio, 1.39; 95% confidence interval, 1.07-1.80) and multivariate analyses (odds ratio, 1.43; 95% confidence interval, 1.05-1.95). CONCLUSIONS. The current results indicated that women who had breast cancer detected by methods other than mammography were slightly more likely to receive guideline-consistent therapy than women who had breast cancer detected by mammography. Future research exploring mode of detection, guideline-consistent treatment, and survival among patients with recently diagnosed breast cancer may inform understanding of factors associated with breast cancer prognosis. C1 [Yabroff, K. Robin; Harlan, Linda C.; Clegg, Limin X.; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Clegg, Limin X.] US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC USA. [Stevens, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA. [Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM Yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI NIH HHS [N01 PC 67000, N01 PC 65064, N01 PC 65107, N01 PC 67001, N01 PC 67005, N01 PC 67006, N01 PC 67007, N01 PC 67008, N01 PC 67009, N01 PC 67010] NR 35 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2008 VL 112 IS 5 BP 1011 EP 1019 DI 10.1002/cncr.23260 PG 9 WC Oncology SC Oncology GA 268HA UT WOS:000253569100009 PM 18189297 ER PT J AU Wheatley-Price, P Asomaning, K Reid, A Zhai, R Su, L Zhou, W Zhu, A Ryan, DP Christiani, DC Liu, G AF Wheatley-Price, Paul Asomaning, Kofi Reid, Amy Zhai, Rihong Su, Li Zhou, Wei Zhu, Andrew Ryan, David P. Christiani, David C. Liu, Geoffrey TI Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma SO CANCER LA English DT Article DE myeloperoxidase; superoxide dismutase; polymorphism; pancreatic cancer ID LUNG-CANCER RISK; MITOCHONDRIAL TARGETING SEQUENCE; GINGIVAL CREVICULAR FLUID; GENETIC POLYMORPHISMS; ANTIOXIDANT ENZYMES; PROSTATE-CANCER; BREAST-CANCER; REDUCED RISK; MNSOD GENE; DISEASE AB BACKGROUND. Pancreatic cancer risk has been linked to chronic pancreatitis and periodontitis, suggesting a role for inflammation in disease etiology. Myeloperoxidase (MPO) and superoxide dismutase (SOD2) are enzymes that regulate reactive oxygen species and contain recognized single nucleotide polymorphisms (SNPs) that confer altered enzyme activity. METHODS. One hundred twenty-two patients with pancreatic cancer and 331 age- and sex-matched controls were analyzed for polymorphisms of the MPO guanine 463 adenine (-G463A) and the SOD2 alanine (Ala)-to-vatine (Val) polymorphism at codon 16 (Ala16Val) genes. Cases and controls were analyzed for associations between these polymorphisms, adjusting for sex, age, history of alcohol use and smoking history. RESULTS. The variant A allele of MPO - G463A was associated with a lower risk of pancreatic cancer (adjusted odds ratio [OR] for pancreatic cancer, 0.57; 95% confidence interval [95% CI], 0.4-0.9; P =.02). The SOD2 homozygous variant genotype (Val/Val was associated with a greater risk of pancreatic cancer (adjusted OR, 1.96; 95% CI, 1.0-3.8; P =.04). Compared with individuals who carried both low-risk alleles (A/- and Ala/-), significantly more cases than controls carried both high-risk genotypes (GIG and Val/Val; adjusted OR, 4.31; 95% CI, 1.8-10; P = .001), or 1 high-risk genotype (adjusted OR, 1.96; 95% CI, 1.1-3.4; P = .01). CONCLUSIONS. Polymorphisms of the inflammatory pathway genes MPO -G463A and SOD2 Ala16Val are associated with elevated pancreatic cancer risk. Oxidative stress may play an important role in pancreatic cancer carcinogenesis. C1 [Wheatley-Price, Paul; Liu, Geoffrey] Princess Margaret Hosp, Dept Med Oncol & Hematol, Dept Med, Toronto, ON M5G 2M9, Canada. [Asomaning, Kofi; Reid, Amy; Zhai, Rihong; Su, Li; Zhou, Wei; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Zhu, Andrew; Ryan, David P.; Christiani, David C.; Liu, Geoffrey] Massachusetts Gen Hosp, Dept Med, Div Hematol & Med Oncol, Boston, MA 02114 USA. [Liu, Geoffrey] Ontario Canc Inst, Dept Med Biophys, Div Appl Mol Oncol, Toronto, ON M4X 1K9, Canada. RP Liu, G (reprint author), Princess Margaret Hosp, Dept Med Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM geoffrey.liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016; OI Wheatley-Price, Paul/0000-0002-3725-9767 NR 51 TC 33 Z9 34 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2008 VL 112 IS 5 BP 1037 EP 1042 DI 10.1002/cncr.23267 PG 6 WC Oncology SC Oncology GA 268HA UT WOS:000253569100012 PM 18205184 ER PT J AU Allen, AM Mentzer, SJ Yeap, BY Soto, R Baldini, EH Rabin, MS Sugarbaker, DJ Bueno, R AF Allen, Aaron M. Mentzer, Steven J. Yeap, Beow Y. Soto, Ricardo Baldini, Elizabeth H. Rabin, Michael S. Sugarbaker, David J. Bueno, Raphael TI Pneumonectomy after chemoradiation - The Dana-Farber Cancer Institute/Brigham and Women's Hospital experience SO CANCER LA English DT Article DE nonsmall cell lung cancer; surgery; chemoradiotherapy; trimodality therapy ID CELL LUNG-CANCER; LONG-TERM SURVIVAL; SEQUENTIAL CHEMORADIOTHERAPY; CONCURRENT CHEMOTHERAPY; OPERATIVE MORTALITY; SLEEVE LOBECTOMY; RESECTION; MORBIDITY; STAGE; THERAPY AB BACKGROUND. The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS. All patients undergoing pneumonectomy after induction therapy at the Brigham and Women's Hospital were retrospectively evaluated for 30-day and 100-day mortality and treatment-related complications with Institutional Review Board approval. Multivariate and univariate analyses for clinical factors correlating with toxicity and/or survival were calculated. RESULTS. Between 1995 and 2005, 73 patients underwent pneumonectomy for NSCLC after induction therapy. All patients received radiation (median dose of 54 gray [Gy]) and 69 patients (95%) received concurrent chemotherapy The median age was 62 years and 43 patients (59%) were male; Thirty-seven patients (51%) had American Joint Committee on Cancer stage IIIA NSCLC, 27 (37%) had stage IIIB, 6 had stage IIB, and 4 had stage IV NSCLC because of a resected solitary brain metastasis. A majority (44; 60%) of patients received the combination of carboplatin and paclitaxel, whereas 15 (21%) received the combination of cisplatin and etoposide. Forty-five patients (62%) underwent left pneumonectomy. With a median follow-up of 28 months, the 1-year and 2-year overall survival rates were 70% and 49%, respectively. The 30-day and 100-day mortality rates were 6% and 10%, respectively. Only 4 of 73 patients (6%) died of acute respiratory distress syndrome. The rate of nonfatal treatment-related morbidity was 11%. On univariate analysis, right-sided pneumonectomy was associated with a higher risk of treatment-related mortality (P = .099). CONCLUSIONS. With an acceptable mortality rate, a single-institutional series demonstrated that trimodality therapy including pneumonectomy can be safely accomplished in patients with advanced NSCLC. C1 [Allen, Aaron M.; Soto, Ricardo; Baldini, Elizabeth H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mentzer, Steven J.; Sugarbaker, David J.; Bueno, Raphael] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Surg, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Rabin, Michael S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Allen, AM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Aallen@lroc.harvard.edu NR 32 TC 26 Z9 27 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2008 VL 112 IS 5 BP 1106 EP 1113 DI 10.1002/cncr.23283 PG 8 WC Oncology SC Oncology GA 268HA UT WOS:000253569100021 PM 18286507 ER PT J AU Hopkins, J Cescon, DW Tse, D Bradbury, P Xu, W Ma, C Wheatley-Price, P Waldron, J Goldstein, D Meyer, F Bairati, I Liu, G AF Hopkins, Jessica Cescon, David W. Tse, Darren Bradbury, Penelope Xu, Wei Ma, Clement Wheatley-Price, Paul Waldron, John Goldstein, David Meyer, Francois Bairati, Isabelle Liu, Geoffrey TI Genetic Polymorphisms and head and neck cancer outcomes: A review SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID SQUAMOUS-CELL CARCINOMA; NUCLEOTIDE EXCISION-REPAIR; S-TRANSFERASE POLYMORPHISMS; 2ND PRIMARY TUMORS; FGFR4 GLY388ARG POLYMORPHISM; ADVANCED COLORECTAL-CANCER; DNA-REPAIR; LUNG-CANCER; PROGNOSTIC-FACTORS; XPD POLYMORPHISMS AB Head and neck cancer (HNC) patients have variable prognoses even within the same clinical stage and while receiving similar treatments. The number of studies of genetic polymorphisms as prognostic factors of HNC outcomes is growing. Candidate polymorphisms have been evaluated in DNA repair, cell cycle, xenobiotic metabolism, and growth factor pathways. Polymorphisms of XRCC1, FGFR, and CCND1 have been consistently associated with HNC survival in at least two studies, whereas most of the other polymorphisms have either conflicting data or were from single studies. Heterogeneity and lack of description of patient populations and lack of accounting for multiple comparisons were common problems in a significant proportion of studies. Despite a large number of exploratory studies, large replication studies in well-characterized HNC populations are warranted. C1 [Hopkins, Jessica; Cescon, David W.; Tse, Darren; Bradbury, Penelope; Wheatley-Price, Paul; Liu, Geoffrey] Princess Margaret Hosp, Dept Med, Div Hematol & Med Oncol, Toronto, ON M5G 2M9, Canada. [Hopkins, Jessica; Cescon, David W.; Tse, Darren; Bradbury, Penelope; Liu, Geoffrey] Ontario Canc Inst, Dept Med Biophys, Div Appl Mol Oncol, Toronto, ON M4X 1K9, Canada. [Hopkins, Jessica] McMaster Univ, Community Med Residency Program, Hamilton, ON, Canada. [Hopkins, Jessica] McMaster Univ, Dept Family Med, Hamilton, ON L8S 4L8, Canada. [Cescon, David W.] Princess Margaret Hosp, Dept Med, Div Gen Internal Med, Toronto, ON M4X 1K9, Canada. [Xu, Wei; Ma, Clement] Princess Margaret Hosp, Biostat Unit, Toronto, ON M4X 1K9, Canada. [Waldron, John] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. [Goldstein, David] Univ Toronto, Dept Otolaryngol, Univ Hlth Network, Toronto, ON M5S 1A1, Canada. [Meyer, Francois; Bairati, Isabelle] Univ Laval, Ctr Rech Cancerol, Quebec City, PQ, Canada. [Liu, Geoffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Liu, G (reprint author), Princess Margaret Hosp, Dept Med, Div Hematol & Med Oncol, Room 7-124,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM geoffrey.liu@uhn.on.ca OI Wheatley-Price, Paul/0000-0002-3725-9767 FU NCI NIH HHS [R01-CA109193, R03-CA110822] NR 111 TC 30 Z9 30 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 490 EP 499 DI 10.1158/1055-9965.EPI-07-2714 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600006 PM 18349267 ER PT J AU Greene, MH Piedmonte, M Alberts, D Gail, M Hensley, M Miner, Z Mai, PL Loud, J Rodriguez, G Basil, J Boggess, J Schwartz, PE Kelley, JL Wakeley, KE Minasian, L Skates, S AF Greene, Mark H. Piedmonte, Marion Alberts, Dave Gail, Mitchell Hensley, Martee Miner, Zoe Mai, Phuong L. Loud, Jennifer Rodriguez, Gustavo Basil, Jack Boggess, John Schwartz, Peter E. Kelley, Joseph L. Wakeley, Katie E. Minasian, Lori Skates, Stephen TI A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: Design and baseline characteristics: A Gynecologic oncology group study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ORAL-CONTRACEPTIVE USE; BRCA2 MUTATION CARRIERS; PROPHYLACTIC OOPHORECTOMY; TUBAL-LIGATION; BREAST-CANCER; PROSPECTIVE COHORT; HEREDITARY BREAST; FALLOPIAN-TUBE; HYSTERECTOMY; CARCINOMA AB Background: Women who are genetically predisposed to ovarian cancer are at very high risk of developing this disease. Although risk-reducing salpingo-oophorectomy (RRSO) and various screening regimens are currently recommended to reduce ovarian cancer risk, the optimal management strategy has not been established nor have multiple additional issues been adequately addressed. We developed a collaboration among the Clinical Genetics Branch (National Cancer Institute's Intramural Research Program), the Gynecologic Oncology Group (GOG), and the Cancer Genetics Network to address these issues. Methods: This is a prospective, international, two-cohort, nonrandomized study of women at genetic risk of ovarian cancer, who chose either to undergo RRSO or screening, at study enrollment. Primary study objectives include quantifying and comparing ovarian and breast cancer incidence in the two study groups, assessing feasibility and selected performance characteristics of a novel ovarian cancer screening strategy (the Risk of Ovarian Cancer Algorithm), evaluating various aspects of quality of life and nononcologic morbidity related to various interventions in at-risk women, and creating a biospecimen repository for subsequent translational research. Results: Study accrual is complete as of November 2006; 2,605 participants enrolled: 1,030 (40%) into the surgical cohort and 1,575 (60%) into the screening cohort. Five years of prospective follow-up ends in November 2011. Verification of BRCA mutation carrier status is under way, either through patient-provided reports from clinical genetic testing done before enrollment or through research-based genetic testing being conducted as part of the protocol. Patient eligibility is currently under evaluation and baseline, surgical, pathology, and outcome data are still being collected. The study design and selected baseline characteristics of cohort members are summarized. Conclusion: This National Cancer Institute intramural/extramural collaboration will provide invaluable prospectively collected observational data on women at high familial ovarian cancer risk, including substantial numbers cf women carrying BRCA1/2 mutations. These data will aid in elucidating the effect of RRSO on breast/ ovarian cancer risk and the effects of two management strategies, on quality of life and other issues that may influence patient care, as well as providing preliminary estimates of test specificity and positive predictive value of a novel ovarian cancer screening strategy. C1 [Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer] NCI, Clin Genet Branch, Rockville, MD 20852 USA. [Gail, Mitchell] NCI, Biostat Branch, Rockville, MD 20852 USA. [Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Rockville, MD 20852 USA. [Piedmonte, Marion; Miner, Zoe] New York State Dept Hlth, Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Alberts, Dave] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85721 USA. [Hensley, Martee] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rodriguez, Gustavo] Evanston NW Healthcare, Evanston, IL USA. [Basil, Jack] St Elizabeth Hosp, Edgewater, KY USA. [Boggess, John] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT USA. [Kelley, Joseph L.] Univ Pittsburgh, Ctr Med, Magee Womens Hosp, Pittsburgh, PA USA. [Wakeley, Katie E.] Tufts Univ New England Med Ctr, London, England. [Skates, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, 6120 Execut Blvd,Room EPS 7032, Rockville, MD 20852 USA. EM greenem@mail.nih.gov FU Intramural NIH HHS [ZIA CP010145-11]; NCI NIH HHS [P50 CA105009, CA 27469, CA 37517, CA086381, CA105009, U01 CA086381, U10 CA027469, U10 CA037517] NR 47 TC 47 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 594 EP 604 DI 10.1158/1055-9965.EPI-07-2703 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600018 PM 18349277 ER PT J AU Feng, QH Hawes, SE Stern, JE Wiens, L Lu, H Dong, ZM Jordanj, CD Kiviatl, NB Vesselle, H AF Feng, Qinghua Hawes, Stephen E. Stern, Joshua E. Wiens, Linda Lu, Hiep Dong, Zhao Ming Jordanj, C. Diana Kiviatl, Nancy B. Vesselle, Hubert TI DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENE PROMOTER METHYLATION; POSITRON-EMISSION-TOMOGRAPHY; ABERRANT METHYLATION; CPG ISLANDS; FLUORODEOXYGLUCOSE UPTAKE; EARLY-DIAGNOSIS; MULTIPLE GENES; HYPERMETHYLATION; ADENOCARCINOMA; P16(INK4A) AB We used MethyLight assays to analyze DNA methylation status of 27 genes on 49 paired cancerous and noncancerous tissue samples from non-small cell lung cancer (NSCLC) patients who underwent surgical resection. Seven genes (RARB, BVES, CDKN2A, KCNH5, RASSF1, CDH13, and RUNX) were found to be methylated significantly more frequently in tumor tissues than in noncancerous tissues. Only methylation of CCND2 and APC was frequently detected in both cancerous and noncancerous tissues, supporting the hypothesis that the methylation of these two genes is a preneoplastic change and may be associated with tobacco smoking exposure. Methylation of any one of eight genes (RASSF1, DAPK1, BVES, CDH13, MGMT, KCNH5, RARB, or CDH1) was present in 80% of NSCLC tissues but only in 14% of noncancerous tissues. Detection of methylation of these genes in blood might have utility in monitoring and detecting tumor recurrence in early-stage NSCLC after curative surgical resection. C1 [Wiens, Linda; Vesselle, Hubert] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Feng, Qinghua; Stern, Joshua E.; Lu, Hiep; Jordanj, C. Diana; Kiviatl, Nancy B.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Hawes, Stephen E.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Dong, Zhao Ming] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Vesselle, H (reprint author), Univ Washington, Sch Med, Dept Radiol, Box 357115, Seattle, WA 98195 USA. EM vesselle@u.washington.edu FU NCI NIH HHS [CA80907, CA115559, CA107264, R01 CA080907-04, R01 CA107264, R01 CA107264-05, R01 CA115559, R01 CA115559-05, R01 CA080907] NR 42 TC 94 Z9 99 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 645 EP 654 DI 10.1158/1055-9965.EPI-07-2518 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600024 PM 18349282 ER PT J AU Mahale, AM Khan, ZAT Igarashi, M Nanjangud, GJ Qiao, RF Yao, S Lee, SW Aaronson, SA AF Mahale, Alka M. Khan, Zahid A. T. Igarashi, Makoto Nanjangud, Gouri J. Qiao, Rui Fang Yao, Shen Lee, Sam W. Aaronson, Stuart A. TI Clonal selection in malignant transformation of human fibroblasts transduced with defined cellular oncogenes SO CANCER RESEARCH LA English DT Article ID HUMAN TUMOR-CELLS; HUMAN-DIPLOID FIBROBLASTS; SMALL-T ANTIGEN; HUMAN BREAST; NEOPLASTIC TRANSFORMATION; MEDIATED TRANSFORMATION; COLORECTAL CANCERS; EPITHELIAL-CELLS; IN-VITRO; TELOMERASE AB Recent evidence has implied that disruption of a limited number of defined cellular pathways is necessary and sufficient for neoplastic conversion of a variety of normal human cell types in tissue culture. We show instead that malignancy in such models results from an iterative process of clonal selection in vitro and/or in vivo. Normal human fibroblasts underwent malignant transformation after transduction with telomerase, cyclin-dependent kinase 4, dominant-negative p53, and activated Ras or MEK. Furthermore, culture conditions favoring overgrowth resulted in clonal selection, which with added Ras or MEK oncogenes led to the emergence of tumorigenic clones. Such tumors showed variable degrees of malignancy with some even exhibiting metastasis. SV40 small t antigen (ST) has been reported to be necessary and sufficient to convert human fibroblasts with these pathway aberrations to a polyclonal tumor. However, we observed that clonal tumors emerged even with ST addition. Genomic instability was markedly increased by p53 and Rb pathway abrogation. Under the same conditions, fibroblasts with these alterations failed to induce tumors, implying that genomic instability may be necessary but not sufficient for malignant transformation. These findings indicate that the minimum number of events required for malignant transformation of human fibroblasts is greater than has been enumerated by such oneogene addition strategies and support a stochastic cancer progression model initiated by four defined cellular alterations. C1 [Mahale, Alka M.; Khan, Zahid A. T.; Igarashi, Makoto; Qiao, Rui Fang; Yao, Shen; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Nanjangud, Gouri J.] Mem Sloan Kettering Canc Ctr, Dept Cell Biol, New York, NY 10021 USA. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM stuart.aaronson@mssm.edu FU NCI NIH HHS [CA085214-08] NR 47 TC 16 Z9 17 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 MAR 1 PY 2008 VL 68 IS 5 BP 1417 EP 1426 DI 10.1158/0008-5472.CAN-07-3021 PG 10 WC Oncology SC Oncology GA 271PW UT WOS:000253802200022 PM 18316605 ER PT J AU Bai, T Luoh, SW AF Bai, Tao Luoh, Shiuh-Wen TI GRB-7 facilitates HER-2/Neu-mediated signal transduction and tumor formation SO CARCINOGENESIS LA English DT Article ID HER2-POSITIVE BREAST-CANCER; CELL-MIGRATION; ADJUVANT CHEMOTHERAPY; ADAPTER PROTEIN; GENE-EXPRESSION; TYROSINE KINASE; ERBB2 AMPLICON; OVARIAN-CANCER; RECEPTOR; AMPLIFICATION AB Growth factor receptor-bound protein-7 (GRB-7), an adaptor molecule, can interact with multiple signal transduction molecules. GRB-7 is amplified concurrently with HER-2/Neu in most, if not all, of breast cancer with chromosome 17q11-21 amplification. GRB-7 gene amplification is associated with RNA over-expression. We show GRB-7 protein is over-expressed by immunoblotting in breast cancer cell lines and primary breast tumors with HER-2/Neu protein over-expression. Over-expression of GRB-7 in MCF-7 breast cancer cells that over-express HER-2/Neu leads to activation of tyrosine phosphorylation of HER-2/Neu. Knockdown of GRB-7 expression in SKBR-3 breast cancer cells with naturally occurring HER-2/Neu gene amplification decreases tyrosine phosphorylation of HER-2/Neu. Activation of HER-2/Neu phosphorylation is associated with increase in tyrosine phosphorylation of phosphoinositide-specific lipase C-gamma-1 (PLC-gamma-1) and recruitment of PLC-gamma-1 to HER-2/Neu protein molecule. Activation of downstream protein kinase C (PKC) pathway is evidenced by increase in the phosphorylation of a common PKC substrate-myristoylated alanine-rich protein kinase C substrate (MARCKS). In addition, over-expression of GRB-7 in MCF-7 breast cancer cells that over-express HER-2/Neu leads to activation of AKT phosphorylation. Knockdown of GRB-7 expression in MB-453 and SKBR-3 breast cancer cells results in decrease in AKT phosphorylation. GRB-7 over-expression therefore facilitates activation of phosphorylation of HER-2/Neu and AKT in breast cancer cells with HER-2/Neu over-expression. GRB-7 over-expression in MCF-7 cells over-expressing HER-2/Neu leads to morphologic change of cells and promotes tumor xenograft growth in nude mice. GRB-7 over-expression therefore plays pivotal roles in activating signal transduction and promoting tumor growth in breast cancer cells with chromosome 17q11-21 amplification. C1 [Bai, Tao; Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Hematol & Med Oncol, Portland, OR 97239 USA. RP Luoh, SW (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Hematol & Med Oncol, Portland, OR 97239 USA. EM luohs@ohsu.edu FU NCI NIH HHS [P30CA069533] NR 40 TC 33 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2008 VL 29 IS 3 BP 473 EP 479 DI 10.1093/carcin/bgm221 PG 7 WC Oncology SC Oncology GA 274NP UT WOS:000254008300003 PM 17916906 ER PT J AU Zabaleta, J Lin, HY Sierra, RA Hall, MC Clark, PE Sartor, OA Hu, JJ Ochoa, AC AF Zabaleta, Jovanny Lin, Hui-Yi Sierra, Rosa A. Hall, M. Craig Clark, Peter E. Sartor, Oliver A. Hu, Jennifer J. Ochoa, Augusto C. TI Interactions of cytokine gene polymorphisms in prostate cancer risk SO CARCINOGENESIS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; INTERLEUKIN-10 PROMOTER; SUSCEPTIBILITY LOCUS; GASTRIC-CANCER; ALPHA PROMOTER; INFLAMMATION; ASSOCIATION; EXPRESSION; CARCINOMA AB Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case-control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)-logit models. African-Americans with the IL10-819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07-1.01], but subjects with the genotype combination of IL1B-511CT/TT and IL10-592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09-6.02). In Caucasians, higher CaP risk was associated with the IL10-1082AG/GG genotype (OR = 3.62, 95% CI = 1.42-9.28), the genotype combination of IL10-1082AA plus IL1B-31TT/TC (OR = 2.92, 95% CI = 1.13-7.55) and the genotype combination of TNF-238GG plus IL10-592AA (OR = 2.14, 95% CI = 1.05-4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk. C1 [Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA. [Lin, Hui-Yi] Univ Alabama, Med Stat Sect, Birmingham, AL 35294 USA. [Sierra, Rosa A.; Ochoa, Augusto C.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70112 USA. [Hall, M. Craig] Wake Forest Univ, Sch Med, Dept Urol, Winston Salem, NC 27157 USA. [Hall, M. Craig] Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. [Clark, Peter E.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA. [Clark, Peter E.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN 37232 USA. [Sartor, Oliver A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hu, Jennifer J.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Hu, Jennifer J.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. RP Zabaleta, J (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Genet, 533 Bolivar St,CSRB 455, New Orleans, LA 70112 USA. EM jzabal@lsuhsc.edu RI Clark, Peter/E-1423-2011 OI Clark, Peter/0000-0002-8006-7015 FU NCI NIH HHS [CA82689, CA107974]; NCRR NIH HHS [M01-RR07122] NR 55 TC 39 Z9 41 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2008 VL 29 IS 3 BP 573 EP 578 DI 10.1093/carcin/bgm277 PG 6 WC Oncology SC Oncology GA 274NP UT WOS:000254008300015 PM 18174250 ER PT J AU Ray, CE Prochazka, A AF Ray, Charles E., Jr. Prochazka, Allan TI The need for anticoagulation following inferior vena cava filter placement: Systematic review SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE anticoagulation; evidence-based medicine; IVC filters; venous interruption ID TECH-LGM FILTER; GREENFIELD FILTER; PULMONARY-EMBOLISM; INTERRUPTION; THROMBOSIS; DEVICES; THROMBOEMBOLISM; COMPLICATIONS; PREVENTION; EXPERIENCE AB Purpose To perform a systemic review to determine the effect of anticoagulation on the rates of venous thromboembolism (pulmonary embolus, deep venous thrombosis, inferior vena cava (IVC) filter thrombosis) following placement of an IVC filter. Methods A comprehensive computerized literature search was performed to identify relevant articles. Data were abstracted by two reviewers. Studies were included if it could be determined whether or not subjects received anticoagulation following filter placement, and if follow-up data were presented. A meta-analysis of patients from all included studies was performed. A total of 14 articles were included in the final analysis, but the data from only nine articles could be used in the meta-analysis; five studies were excluded because they did not present raw data which could be analyzed in the meta-analysis. A total of 1,369 subjects were included in the final meta-analysis. Results The summary odds ratio for the effect of anticoagulation on venous thromboembolism rates following filter deployment was 0.639 (95% CI 0.351 to 1.159, p = 0.141). There was significant heterogeneity in the results from different studies [Q statistic of 15.95 (p = 0.043)]. Following the meta-analysis, there was a trend toward decreased venous thromboembolism rates in patients with post-filter anticoagulation (12.3% vs. 15.8%), but the result failed to reach statistical significance. Conclusion Inferior vena cava filters can be placed in patients who cannot receive concomitant anticoagulation without placing them at significantly higher risk of development of venous thromboembolism. C1 [Ray, Charles E., Jr.] Univ Colorado Denver & Hlth Sci Ctr, Dept Radiol, Aurora, CO 80045 USA. [Ray, Charles E., Jr.] Univ Colorado Denver & Hlth Sci Ctr, Dept Clin Sci, Aurora, CO 80045 USA. [Prochazka, Allan] Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Aurora, CO USA. [Prochazka, Allan] Denver VA Med Ctr, Dept Ambulatory Care, Denver, CO USA. RP Ray, CE (reprint author), Univ Colorado Denver & Hlth Sci Ctr, Dept Radiol, Mail Stop C276,Leprino Off Bldg,12401 E 17th Ave, Aurora, CO 80045 USA. EM charles.ray@uchsc.edu NR 40 TC 21 Z9 24 U1 0 U2 4 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 MAR PY 2008 VL 31 IS 2 BP 316 EP 324 DI 10.1007/s00270-007-9244-x PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 275QT UT WOS:000254087400011 PM 18080710 ER PT J AU Chi, YW Jaff, MR AF Chi, Yung-Wei Jaff, Michael R. TI Optimal risk factor modification and medical management of the patient with peripheral arterial disease SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Review DE medical management; peripheral arterial occlusive disease; risk factor modification ID RANDOMIZED CONTROLLED-TRIALS; ANKLE-BRACHIAL INDEX; JOINT NATIONAL COMMITTEE; RECEPTOR PARTIAL AGONIST; PLACEBO-CONTROLLED TRIAL; PRIMARY-CARE PATIENTS; HIGH BLOOD-PRESSURE; DOUBLE-BLIND TRIAL; INTERMITTENT CLAUDICATION; VASCULAR-DISEASE AB Peripheral arterial occlusive disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. It is defined by atherosclerotic obstruction of the abdominal aorta and arteries to the legs that reduces arterial flow during exercise and/or at rest, and is a common manifestation of systemic atherosclerosis. PAD represents a marker for premature cardiovascular events, and in patients with PAD, even in the absence of a history of myocardial infarction (MI) or ischemic stroke, they have approximately the same relative risk of death from cardiovascular causes as do patients with a history of coronary or cerebrovascular disease. In addition, their death rate from all causes is approximately equal in men and women and is elevated even in asymptomatic patients. The major risk factors for PAD are the well defined atherosclerotic risks such as diabetes mellitus, cigarette smoking, advanced age, hyperlipidemia, and hypertension. Due to the presence of these risk factors, the systemic nature of atherosclerosis, and the high risk of ischemic events, patients with PAD should be candidates for aggressive secondary prevention strategies including aggressive risk factor modification, antiplatelet therapy, lipid lowering therapy and antihypertensive treatment. This article reviews the current medical treatment and risk factor modification of patients with PAD. (C) 2008 Wiley-Liss, Inc. C1 [Chi, Yung-Wei] Ochsner Clin Fdn, Ochsner Heatr & Vasc Inst, Dept Cardiol, Sect Vasc Med, New Orleans, LA USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Med, Boston, MA USA. RP Chi, YW (reprint author), Ochsner Med Ctr, Dept Cardiol, Sect Vasc Med, 2005 Vet Blvd, Metairie, LA 70002 USA. EM ychi@ochsner.org NR 136 TC 21 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAR 1 PY 2008 VL 71 IS 4 BP 475 EP 489 DI 10.1002/ccd.21401 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272SK UT WOS:000253879900003 PM 18307227 ER PT J AU Flanagan, AM Letai, A AF Flanagan, A. M. Letai, A. TI BH3 domains define selective inhibitory interactions with BHRF-1 and KSHVBCL-2 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; BCL-2; BHRF-1; KSHVBCL-2; mitochondria; BIM; BH3; cancer; Epstein-Barr virus; Kaposi's sarcoma herpesvirus ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; MULTIPLE SEQUENCE ALIGNMENT; KAPOSIS-SARCOMA; CELL-DEATH; BCL-2 HOMOLOG; VIRAL HOMOLOG; PROTEIN PROTECTS; APOPTOSIS; BAX AB The Epstein-Barr and Kaposi's sarcoma gamma-herpesviruses (KSHVs) are associated with certain cancers, and encode B-cell leukemia/lymphoma 2 (BCL-2) homologs, BHRF-1 and KSHV BCL-2, respectively. Little is known, however, about the molecular interactions allowing viral BCL-2 homologs to mediate their anti-apoptotic function. Cellular anti-apoptotic proteins, such as BCL-2 and MCL-1, prevent death via selective interactions with pro-death BH3-only proteins. To investigate whether BHRF-1 and KSHV BCL-2 function similarly, we made recombinant BHRF-1 and KSHV BCL-2 proteins. We identified the individual binding patterns for BHRF-1 and KSHV BCL-2 to BH3 domains. These studies surprisingly showed that KSHV BCL-2 is more closely related to MCL-1 than to BCL-2, a result confirmed by sequence analysis. GST-BHRF-1 and GST-KSHV BCL-2 bound BH3-only family proteins from human cells. BHRF-1 protected mammalian cells from growth factor withdrawal, etoposide and adriamycin. We found that both BCL-2 and BHRF-1 sequestered pro-death BH3-only proteins under growth factor-deficient conditions. Finally, we tested the ability of a panel of BH3 peptides to inhibit BHRF-1 and KSHV BCL-2 function in a mitochondrial model of apoptosis. We found that each could be inhibited by the select group of BH3 peptides identified in our binding assay. Our studies define the biochemical interactions underlying BHRF-1 and KSHV BCL-2 anti-apoptotic function, and identify peptides that are prototypic inhibitors of this function. C1 [Flanagan, A. M.; Letai, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530 B,44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [K08 CA102548-05, K08 CA10254, K08 CA102548] NR 43 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 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2008 VL 15 IS 3 BP 580 EP 588 DI 10.1038/sj.cdd.4402292 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 263TR UT WOS:000253239900016 PM 18084238 ER PT J AU Schmidt, PJ Toran, PT Giannetti, AM Bjorkman, PJ Andrews, NC AF Schmidt, Paul J. Toran, Paul T. Giannetti, Anthony M. Bjorkman, Pamela J. Andrews, Nancy C. TI The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression SO CELL METABOLISM LA English DT Article ID HEREDITARY HEMOCHROMATOSIS PROTEIN; IRON-METABOLISM; TRANSGENIC MICE; CRYSTAL-STRUCTURE; HEPATIC IRON; LIVER; BINDING; ABSORPTION; OVERLOAD; ANEMIA AB Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1). We developed mutant mouse strains to gain insight into the role of the Hfe/Tfr1 complex in regulating iron homeostasis. We introduced mutations into a ubiquitously expressed Tfr1 transgene or the endogenous Tfr1 locus to promote or prevent the Hfe/Tfr1 interaction. Under conditions favoring a constitutive Hfe/Tfr1 interaction, mice developed iron overload attributable to inappropriately low expression of the hormone hepcidin. In contrast, mice carrying a mutation that interferes with the Hfe/Tfr1 interaction developed iron deficiency associated with inappropriately high hepcidin expression. High-level expression of a liver-specific Hfe transgene in Hfe(-/-) mice was also associated with increased hepcidin production and iron deficiency. Together, these models suggest that Hfe induces hepcidin expression when it is not in complex with Tfr1. C1 [Schmidt, Paul J.; Toran, Paul T.; Andrews, Nancy C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Schmidt, Paul J.; Toran, Paul T.; Andrews, Nancy C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Giannetti, Anthony M.; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Andrews, Nancy C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM nancy.andrews@duke.edu OI Andrews, Nancy/0000-0003-0243-4462 FU NICHD NIH HHS [P30 HD018655]; NIDDK NIH HHS [K01 DK074410, K01 DK074410-01, P30 DK049216, P30 DK49216-14, R01 DK053813, R01 DK053813-08, R01 DK53813] NR 45 TC 175 Z9 183 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR PY 2008 VL 7 IS 3 BP 205 EP 214 DI 10.1016/j.cmet.2007.11.016 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 270NK UT WOS:000253727300007 PM 18316026 ER PT J AU Mesaros, A Koralov, SB Rother, E Wunderlich, FT Ernst, MB Barsh, GS Rajewsky, K Bruning, JC AF Mesaros, Andrea Koralov, Sergei B. Rother, Eva Wunderlich, F. Thomas Ernst, Marianne B. Barsh, Gregory S. Rajewsky, Klaus Bruening, Jens C. TI Activation of stat3 signaling in AgRP neurons promotes locomotor activity SO CELL METABOLISM LA English DT Article ID AGOUTI-RELATED-PROTEIN; HYPOTHALAMIC ARCUATE NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; LEPTIN-RECEPTOR; POMC NEURONS; WEIGHT HOMEOSTASIS; EXPRESSING NEURONS; GENE-EXPRESSION; ENERGY-BALANCE; DEFICIENT MICE AB Leptin, an adipocyte-derived hormone, acts on hypothalamic neurons located in the arcuate nucleus (ARC) of the hypothalamus to regulate energy homeostasis. One of the leptin-regulated neuronal subtypes in the ARC are agouti-related peptide (AgRP)-expressing neurons, which are involved in the regulation of food intake and are directly inhibited by leptin. Leptin activates the signal transducer and activator of transcription 3 (Stat3), but the role of Stat3 in the regulation of AgRP neurons is unclear. Here we show that mice expressing a constitutively active version of Stat3 selectively in AgRP neurons are lean and exhibit relative resistance to diet-induced obesity. Surprisingly, this phenotype arises from increased locomotor activity in the presence of unaltered AgRP expression. These data demonstrate that Stat3-dependent signaling in AgRP neurons in the ARC controls locomotor activity independently of AgRP regulation. C1 [Mesaros, Andrea; Rother, Eva; Wunderlich, F. Thomas; Ernst, Marianne B.; Bruening, Jens C.] Univ Cologne, Ctr Mol Med Cologne, Inst Genet, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. [Mesaros, Andrea; Rother, Eva; Wunderlich, F. Thomas; Ernst, Marianne B.; Bruening, Jens C.] Univ Cologne, Cologne Excellence Cluster Cellular Strees Respon, D-50674 Cologne, Germany. [Koralov, Sergei B.; Rajewsky, Klaus] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Barsh, Gregory S.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Bruning, JC (reprint author), Univ Cologne, Ctr Mol Med Cologne, Inst Genet, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. EM jens.bruening@uni-koeln.de NR 53 TC 63 Z9 64 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR PY 2008 VL 7 IS 3 BP 236 EP 248 DI 10.1016/j.cmet.2008.01.007 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 270NK UT WOS:000253727300010 PM 18316029 ER PT J AU Stadtfeld, M Maherali, N Breault, DT Hochedlinger, K AF Stadtfeld, Matthias Maherali, Nimet Breault, David T. Hochedlinger, Konrad TI Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse SO CELL STEM CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; EXPRESSION; GENERATION; ADULT; DIFFERENTIATION; VIRUS; LINES; INDUCTION; ADHESION AB Ectopic expression of the transcription factors Oct4, Sox2, c-Myc, and Klf4 in fibroblasts generates induced pluripotent stem (iPS) cells. Little is known about the nature and sequence of molecular events accompanying nuclear reprogramming. Using doxycycline-inducible vectors, we have shown that exogenous factors are required for about 10 days, after which cells enter a self-sustaining pluripotent state. We have identified markers that define cell populations prior to and during this transition period. While downregulation of Thy1 and subsequent upregulation of SSEA-1 occur at early time points, reactivation of endogenous Oct4, Sox2, telomerase, and the silent X chromosome mark late events in the reprogramming process. Cell sorting with these markers allows for a significant enrichment of cells with the potential to become iPS cells. Our results suggest that factor-induced reprogramming is a gradual process with defined intermediate cell populations that contain the majority of cells poised to become iPS cells. C1 [Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02115 USA. [Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Breault, David T.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Breault, David T.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02115 USA. EM khochedlinger@helix.mgh.harvard.edu OI Stadtfeld, Matthias/0000-0002-5852-9906 FU NICHD NIH HHS [R01 HD058013]; NIH HHS [DP2 OD003266, DP2 OD003266-01] NR 35 TC 473 Z9 500 U1 6 U2 42 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR PY 2008 VL 2 IS 3 BP 230 EP 240 DI 10.1016/j.stem.2008.02.001 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 274RD UT WOS:000254017700010 PM 18371448 ER PT J AU Rhodes, KE Gekas, C Wang, Y Lux, CT Francis, CS Chan, DN Conway, S Orkin, SH Yoder, MC Mikkola, HKA AF Rhodes, Katrin E. Gekas, Christos Wang, Yanling Lux, Christopher T. Francis, Cameron S. Chan, David N. Conway, Simon Orkin, Stuart H. Yoder, Mervin C. Mikkola, Hanna K. A. TI The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation SO CELL STEM CELL LA English DT Article ID MURINE YOLK-SAC; DEFINITIVE HEMATOPOIESIS; MOUSE EMBRYO; ENDOTHELIAL-CELLS; UMBILICAL-CORD; AGM REGION; IN-VITRO; EXPRESSION; ALLANTOIS; NICHE AB The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myeloerythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation. C1 [Rhodes, Katrin E.; Gekas, Christos; Wang, Yanling; Francis, Cameron S.; Chan, David N.; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Mikkola, Hanna K. A.] Univ Calif Los Angeles, Eli Edyth Broad Ctr Regenerat Med & Stem Cell Res, Los Angeles, CA 90095 USA. [Mikkola, Hanna K. A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Mikkola, Hanna K. A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Lux, Christopher T.; Conway, Simon; Yoder, Mervin C.] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Mikkola, HKA (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. EM hmikkola@mcdb.ucla.edu RI Chan, David/F-1686-2013; Gekas, Christos/M-3209-2015 OI Gekas, Christos/0000-0002-3429-4145 FU NHLBI NIH HHS [R01 HL097766, HL63169, R01 HL063169, R01 HL063169-09]; NIDDK NIH HHS [DK069659, R21 DK069659, R21 DK069659-03]; NIGMS NIH HHS [GM07185, T32 GM007185] NR 63 TC 146 Z9 157 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR PY 2008 VL 2 IS 3 BP 252 EP 263 DI 10.1016/j.stem.2008.01.001 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 274RD UT WOS:000254017700012 PM 18371450 ER PT J AU Fleming, HE Janzen, V Lo Celso, C Guo, J Leahy, KM Kronenberg, HM Scadden, DT AF Fleming, Heather E. Janzen, Viktor Lo Celso, Cristina Guo, Jun Leahy, Kathleen M. Kronenberg, Henry M. Scadden, David T. TI Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo SO CELL STEM CELL LA English DT Article ID BETA-CATENIN; PROGENITOR CELLS; GAMMA-CATENIN; EX-VIVO; DIFFERENTIATION; ENGRAFTMENT; BONE; 5-FLUOROURACIL; REPOPULATION; ACTIVATION AB Wingless (Wnt) is a potent morphogen demonstrated in multiple cell lineages to promote the expansion and maintenance of stem and progenitor cell populations. Writ effects are highly context dependent, and varying effects of Wnt signaling on hematopoietic stem cells (HSCs) have been reported. We explored the impact of Wnt signaling in vivo, specifically in the context of the HSC niche by using an osteoblast-specific promoter driving expression of the paninhibitor of canonical Wnt signaling, Dickkopf1 (Dkk1). Here we report that Wnt signaling was markedly inhibited in HSCs and, unexpectedly given prior reports, reduction in HSC Wnt signaling resulted in reduced p21Cip1 expression, increased cell cycling, and a progressive decline in regenerative function after transplantation. This effect was microenvironment determined, but irreversible if the cells were transferred to a normal host. Wnt pathway activation in the niche is required to limit HSC proliferation and preserve the reconstituting function of endogenous hematopoietic stem cells. C1 [Fleming, Heather E.; Janzen, Viktor; Lo Celso, Cristina; Leahy, Kathleen M.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Guo, Jun; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Fleming, Heather E.; Janzen, Viktor; Lo Celso, Cristina; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu OI Lo Celso, Cristina/0000-0002-1163-4207 FU NHLBI NIH HHS [R01 HL044851-13, R01 HL044851-14, R01 HL044851-17, U54 HL081030, R01 HL044851-19, R01 HL044851-11, R01 HL044851-15, R01 HL044851, R01 HL044851-10, HL044851, R01 HL044851-16A1, HL081030, R01 HL044851-18, R01 HL044851-12, R01 HL044851-09, HL07623, R01 HL044851-18W1, R01 HL044851-20, U54 HL081030-01]; NIDDK NIH HHS [DK050234] NR 54 TC 268 Z9 278 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR PY 2008 VL 2 IS 3 BP 274 EP 283 DI 10.1016/j.stem.2008.01.003 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 274RD UT WOS:000254017700014 PM 18371452 ER PT J AU Noonan, EJ Fournier, G Hightower, LE AF Noonan, Emily J. Fournier, Gregory Hightower, Lawrence E. TI Surface expression of Hsp70B' in response to proteasome inhibition in human colon cells SO CELL STRESS & CHAPERONES LA English DT Article DE cell surface; Hsp70B'; proteasome inhibitor; colon cells; phylogeny ID HEAT-SHOCK-PROTEIN; INDUCIBLE IMMUNOGENIC DETERMINANT; NATURAL-KILLER-CELLS; HUMAN TUMOR-CELLS; HEAT-SHOCK-PROTEIN-70 HSP70; SARCOMA-CELLS; LYSIS; FAMILY; RECOGNITION; SENSITIVITY AB Hsp70B' was expressed on the surface of HT-29 and CRL-1809 but not SW-480 human colon cell lines in response to proteasome inhibition as detected using flow cytometry. Surface expression was not detected under non-stress conditions nor was heat shock an inducer of surface expression in the three cell lines tested. Phylogenetic analysis indicated that the Hsp70B' protein sequence was most closely related to another major inducible human Hsp70, Hsp72. Hsp70B' appeared to be recently diverged, as homologs for Hsp70B' have not been found in rodents. Hsp72 and Hsp70B' shared 100% amino acid sequence identity in their predicted peptide-binding regions suggesting that they bind the same peptide substrates, perhaps in extracellular antigen presentation. Amino acid sequence differences were concentrated in the lid regions and the C-terminal domains raising the possibility that Hsp72 and Hsp70B' bind different co-chaperones or cell surface receptors. C1 [Noonan, Emily J.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Noonan, Emily J.; Fournier, Gregory; Hightower, Lawrence E.] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. RP Noonan, EJ (reprint author), San Francisco VA Med Ctr, 4150 Clement St 151H, San Francisco, CA 94121 USA. EM emily.noonan@gmail.com FU NIEHS NIH HHS [P30 ES003828, ES03828] NR 25 TC 19 Z9 19 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD MAR PY 2008 VL 13 IS 1 BP 105 EP 110 DI 10.1007/s12192-007-0003-3 PG 6 WC Cell Biology SC Cell Biology GA 275QV UT WOS:000254087600012 PM 18347947 ER PT J AU van Poll, D Parekkadan, B Rinkes, IHMB Tilles, AW Yarmush, ML AF van Poll, D. Parekkadan, B. Rinkes, I. H. M. Borel Tilles, A. W. Yarmush, M. L. TI Mesenchymal Stem Cell Therapy for Protection and Repair of Injured Vital Organs SO CELLULAR AND MOLECULAR BIOENGINEERING LA English DT Review DE Mesenchymal stem cells; Cytokines; Growth factors; Injury; Tissue injury; Vital organs; Liver; Heart; Kidney; Lung; Brain; Regeneration; Apoptosis; Paracrine; Angiogenesis; Inflammation; Immune cells; Fulminant hepatic failure ID MARROW STROMAL CELLS; ACUTE-RENAL-FAILURE; BONE-MARROW; IN-VITRO; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; RAT MODEL; CARDIOMYOCYTE PHENOTYPE; LIVER FIBROSIS; T-CELLS AB Recently there has been a paradigm shift in what is considered to be the therapeutic promise of mesenchymal stem cells (MSCs) in diseases of vital organs. Originally, research focused on MSCs as a source of regenerative cells by differentiation of transplanted cells into lost cell types. It is now clear that trophic modulation of inflammation, cell death, fibrosis, and tissue repair are the main mechanisms of MSC therapy. Delivery of growth factors, cytokines, and other signaling molecules secreted by MSCs is often sufficient to obtain the therapeutic effects. In this article, we provide an overview of the current knowledge on trophic mechanisms of MSC therapy in disease models of vital organs. Important issues regarding the optimal delivery methods of MSC therapy are discussed and critical gaps in our knowledge hampering experimental progress and clinical implementation are identified. C1 [van Poll, D.; Parekkadan, B.; Tilles, A. W.; Yarmush, M. L.] Harvard Univ, Sch Med, Surg Serv, Boston, MA 02114 USA. [van Poll, D.; Parekkadan, B.; Tilles, A. W.; Yarmush, M. L.] Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [van Poll, D.; Rinkes, I. H. M. Borel] Univ Utrecht, Univ Med Ctr, Dept Surg, Utrecht, Netherlands. [Parekkadan, B.; Yarmush, M. L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org NR 101 TC 20 Z9 20 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1865-5025 J9 CELL MOL BIOENG JI Cell. Mol. Bioeng. PD MAR PY 2008 VL 1 IS 1 BP 42 EP 50 DI 10.1007/s12195-008-0001-2 PG 9 WC Cell & Tissue Engineering; Biophysics; Cell Biology SC Cell Biology; Biophysics GA 494NY UT WOS:000269821600007 ER PT J AU Schaechter, JD Perdue, KL AF Schaechter, Judith D. Perdue, Katherine L. TI Enhanced cortical activation in the contralesional hemisphere of chronic stroke patients in response to motor skill challenge SO CEREBRAL CORTEX LA English DT Article DE cerebral ischemia; functional recovery; motor tasks; MRI/fMRI; neuroplasticity ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY SOMATOSENSORY CORTEX; SEQUENTIAL FINGER MOVEMENTS; POSTERIOR PARIETAL CORTEX; WELL-RECOVERED PATIENTS; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; AGE-RELATED-CHANGES; FUNCTIONAL MRI AB The brain processes involved in the restoration of motor skill after hemiparetic stroke are not fully understood. The current study compared cortical activity in chronic stroke patients who successfully recovered hand motor skill and normal control subjects during performance of kinematically matched unskilled and skilled hand movements using functional magnetic resonance imaging. We found that cortical activation during performance of the unskilled movement was increased in the patients relative to controls in the contralesional primary sensorimotor cortex. Performance of the skilled movement elicited increased activation in the patients relative to controls in the contralesional primary sensorimotor cortex, ventral premotor cortex, supplementary motor area/cingulate, and occipitoparietal cortex. Further, the activation change in the contralesional occipitoparietal cortex was greater in the patients relative to controls with the increase in motor skill challenge. Kinematic differences, mirror movements, and residual motor deficits did not account for the enhanced activation in the contralesional cortices in the patients. These results suggest that activation in the contralesional cortical network was enhanced as a function of motor skill challenge in stroke patients with good motor recovery. The findings of the current study suggest that successful recovery of motor skill after hemiparetic stroke involves participation of the contralesional cortical network. C1 [Schaechter, Judith D.; Perdue, Katherine L.] Massachusetts Gen Hosp, MIT, HMS Athinoula A Marinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Schaechter, Judith D.; Perdue, Katherine L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Schaechter, JD (reprint author), Massachusetts Gen Hosp, MIT, HMS Athinoula A Marinos Ctr Biomed Imaging, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM judith@nmr.mgh.harvard.edu RI Perdue, Katherine/D-4306-2013 OI Perdue, Katherine/0000-0003-2846-3149 FU NCRR NIH HHS [P41-RR14075]; NICHD NIH HHS [K23-HD044425] NR 77 TC 51 Z9 53 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2008 VL 18 IS 3 BP 638 EP 647 DI 10.1093/cercor/bhm096 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 267DP UT WOS:000253490000014 PM 17602141 ER PT J AU Restrepo, MI Mortensen, EM Velez, JA Frei, C Anzueto, A AF Restrepo, Marcos I. Mortensen, Eric M. Velez, Jose A. Frei, Christopher Anzueto, Antonio TI A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU SO CHEST LA English DT Article DE critical care; ICU; microbiology; mortality; outcome and process assessment; pneumonia ID INTENSIVE-CARE-UNIT; ANTIMICROBIAL THERAPY; RISK-FACTORS; PROGNOSIS; EPIDEMIOLOGY; MANAGEMENT; GUIDELINES; MORTALITY; OUTCOMES; ADULTS AB Background: Limited information is available on the health-care utilization of hospitalized patients with community-acquired pneumonia (CAP) depending on the location of care. Our aim was to compare the clinical characteristics, etiologies, and outcomes of patients with CAP who were admitted to the ICU with those admitted who were to the ward service. Methods: A retrospective cohort study, at two tertiary teaching hospitals, one of which was a Veterans Affairs hospital, and the other a county hospital. Eligible subjects had been admitted to the hospital with a diagnosis of CAP between January 1, 1999, and December 31, 2001, had A confirmatory chest radiograph, and a hospital discharge International Classification of Diseases, ninth revision, diagnosis of pneumonia. Subjects were excluded from the study if they had designated "comfort measures only" or had been transferred from another acute care hospital or were nursing home patients. Bivariate and multivariable analysis evaluated 30-day and 90-day mortality as the dependent measures. Results: Data were abstracted on 730 patients (ICU, 145 patients; wards, 585 patients). Compared to ward patients, ICU patients were more likely to be male (p = 0.001), and to have congestive heart failure (p = 0.01) and COPD (p = 0.01). ICU patients also had higher mean pneumonia severity index scores (112 [SD, 35] vs 83 [SD, 30], respectively; p = 0.02). Patients admitted to the ICU had a longer mean length of hospital stay (12 days [SD, 10 days] vs 7 days [SD, 17 days], respectively; p = 0.07), and a higher 30-day mortality rate (23% vs 4%, respectively; p < 0.001) and 90-day mortality rate (28% vs 8%, respectively; p < 0.001) compared to ward patients. Conclusions: ICU patients present with more severe disease and more comorbidities. ICU patients stay longer in the hospital and have a much higher mortality rate when compared to ward patients. Management strategies should be designed to improve clinical outcomes in ICU patients. C1 [Restrepo, Marcos I.; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, ALMD, VERDICT 11C6, San Antonio, TX 78229 USA. [Velez, Jose A.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Frei, Christopher] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharm, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst, ALMD, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM rostrepom@uthsca.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Howard Hughes Medical Institute [00378-001] NR 32 TC 82 Z9 90 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2008 VL 133 IS 3 BP 610 EP 617 DI 10.1378/chest.07-1456 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 273LV UT WOS:000253933300007 PM 17989157 ER PT J AU Doungchawee, G Kositanont, U Niwetpathomwat, A Inwisai, T Sagarasaeranee, P Haake, DA AF Doungchawee, Galayanee Kositanont, Uraiwan Niwetpathomwat, Anuchai Inwisai, Tasanee Sagarasaeranee, Plyyonk Haake, David A. TI Early diagnosis of leptospirosis by immunoglobulin M immunoblot testing SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MICROSCOPIC AGGLUTINATION-TEST; SURFACE-EXPOSED LIPOPROTEIN; HUMAN IMMUNE-RESPONSE; OUTER-MEMBRANE; CONTROLLED-TRIAL; PROTEINS; INFECTION; SERODIAGNOSIS; ANTIBODY; ANTIGEN AB There is an urgent need for the development of serodiagnostic approaches with improved sensitivity for patients with acute leptospirosis. Immunoblots were performed on 188 sera collected from 74 patients with laboratory-confirmed early leptospiral infection to detect immunoglobulin M (IgM) antibodies to antigens pooled from 10 leptospiral strains prevalent in Thailand. Sera from patients with other febrile diseases served as controls. IgM reactivity to seven distinct antigens, with apparent molecular masses of 14 to 18, 19 to 23, 24 to 30, 32, 35/36, 37, and 41/42 kDa, was observed. The low-molecular-mass 14- to 18-kDa band was the most frequently detected antigen, being recognized in sera from 82.4% of patients during the first 3 days after the onset of symptoms. We evaluated the accuracy of the IgM immunoblot (IgM-IB) test by using reactivity to the 14- to 18-kDa band and/or at least two bands among the 19- to 23-, 24- to 30-, 32-, 35/36-, 37-, and 41/42- kDa antigens as the diagnostic criterion. The sensitivities of the IgM-IB test and the microscopic agglutination test (MAT) were 88.2% and 2.0%, respectively, with sera from patients 1 to 3 days after the onset of symptoms. In contrast, the IgM-IB test was positive with only 2/48 (4.2%) sera from patients with other febrile illnesses. The high sensitivity and specificity of the IgM-IB test for acute leptospirosis would provide greatly improved diagnostic accuracy for identification of patients who would benefit from early antibiotic intervention. In addition, the antigens identified by the IgM-IB test may serve as components of a rapid, accurate, point-of-care diagnostic test for early leptospirosis. C1 [Doungchawee, Galayanee; Niwetpathomwat, Anuchai; Inwisai, Tasanee] Mahidol Univ, Fac Sci, Dept Pathol, Bangkok 10400, Thailand. [Kositanont, Uraiwan] Mahidol Univ, Siriraj Hosp, Dept Microbiol, Fac Med, Bangkok 10700, Thailand. [Sagarasaeranee, Plyyonk] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Doungchawee, G (reprint author), Mahidol Univ, Fac Sci, Dept Pathol, Bangkok 10400, Thailand. EM scgdu@mahidol.ac.th OI Doungchawee, Galayanee/0000-0002-7463-8096 FU Department of Disease Control; Ministry of Public Health, Thailand; VA Medical Research funds; NIH/NIAID [AI-34431] FX We are grateful to Albert I. Ko and Visith Thongboonkerd for their useful comments. We thank Oranard Wattanawong and the staff of the Department of Disease Control, Ministry of Public Health, Kannika Niwatayakul of Loei Provincial Hospital, Thailand, and Apichat Pradermwong and Kanjana Sirisidth of Mahidol University.; This study was supported by grants from the Department of Disease Control, Ministry of Public Health, Thailand. D. A. H. was supported by VA Medical Research funds and by NIH/NIAID grant AI-34431. NR 48 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2008 VL 15 IS 3 BP 492 EP 498 DI 10.1128/CVI.00152-07 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 340TA UT WOS:000258666700014 PM 18184827 ER PT J AU Overmoyer, B AF Overmoyer, Beth TI Options for the treatment of patients with taxane-refractory metastatic breast cancer SO CLINICAL BREAST CANCER LA English DT Article DE albumin-bound paclitaxel; capecitabine; epothilones; eribulin; gemcitabine; ixabepilone; vinflunine; vinorelbine ID PHASE-II TRIAL; PEGYLATED LIPOSOMAL DOXORUBICIN; EPOTHILONE-B ANALOG; ALBUMIN-BOUND PACLITAXEL; IXABEPILONE BMS-247550; PLUS CAPECITABINE; 1ST-LINE THERAPY; CLINICAL-TRIAL; SALVAGE CHEMOTHERAPY; PRETREATED PATIENTS AB The application of taxane chemotherapy to the treatment of early-stage and advanced breast cancer has resulted in significant improvements in disease-free and overall survival. As a consequence of these improvements in disease outcome, oncologists; must face the new challenge of developing additional therapies that are effective against taxane-resistant disease and are associated with a favorable toxicity profile. This article discusses some of the chemotherapeutic options available for the treatment of patients with taxane-resistant metastatic breast cancer. Newer formulations of traditional microtubule-stabilizing agents, such as albumin-bound paclitaxel, which uses a more favorable vehicle for administration compared with conventional paclitaxel, have demonstrated efficacy in this setting. Several novel microtubule-targeting agents have been shown to be less susceptible to traditional mechanisms of taxane resistance, such as the multidrug resistance phenotype associated with increased activity of the P-glycoprotein drug efflux system and the development of structural changes in tubulin. Examples of these therapies include the vinca alkaloids, such as vinorelbine and vinflunine; epothilones; and eribulin. Traditional antimetabolites, such as gemcitabine and capecitabine, used as monotherapy or combination chemotherapy have also shown efficacy in the treatment of patients with taxane-resistant breast cancer. A greater understanding of the mechanism of drug resistance, as it pertains to taxanes, will enable further development and the effective application of chemotherapeutic agents that will circumvent drug resistance and result in improvement in breast cancer control. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Overmoyer, B (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bovermoyer@partners.org NR 83 TC 18 Z9 19 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD MAR PY 2008 VL 8 SU 2 BP S61 EP S70 DI 10.3816/CBC.2008.s.002 PG 10 WC Oncology SC Oncology GA 278JH UT WOS:000254281200002 PM 18637401 ER PT J AU Dowlati, A Gray, R Sandler, AB Schiller, JH Johnson, DH AF Dowlati, Afshin Gray, Robert Sandler, Alan B. Schiller, Joan H. Johnson, David H. TI Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab - an eastern cooperative oncology group study SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID THROMBOTIC THROMBOCYTOPENIC PURPURA; E-SELECTIN; PHASE-I; CLINICOPATHOLOGICAL FEATURES; PROGNOSTIC-FACTORS; COLORECTAL-CANCER; SERUM-LEVELS; MARKERS; CARCINOMA; EXPRESSION AB Background: E4599 was a phase II/phase III trial, in which 878 patients with advanced non-small cell lung cancer were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (BPC arm). Survival and progression-free survival were superior on the BPC arm. The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble intercellular adhesion molecule (ICAM) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis. Materials and Methods: Prospective correlates included measurements of pretreatment plasma VEGF, as well as pretreatment and week 7, bFGF, ICAM, and E-selectin. Low and high levels were defined as less than or equal to or more than the median. Results: E-selectin (P < 0.0001) showed a decrease and bFGF showed an increase (P = 0.004) from baseline at week 7, which were similar in both arms. Baseline ICAM showed significant associations with response and survival in both groups. Patients with low baseline ICAM had a higher response rate (32% versus 14%; P = 0.02), better overall survival (P = 0.00005), and better 1-year survival (65% versus 25%) than those with high ICAM, respectively, regardless of treatment arm. Patients with high VEGF levels were more likely to respond to BPC compared with PC, but this was not predictive of survival. The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels (53% reduction in the progression-free survival hazard rate). Conclusions: In this study, baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab. VEGF levels were predictive of response to bevacizumab but not survival. C1 [Dowlati, Afshin] Univ Hosp Case Med Ctr, Cleveland, OH 44016 USA. [Dowlati, Afshin] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sandler, Alan B.; Johnson, David H.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Sandler, Alan B.; Johnson, David H.] Vanderbilt Univ, Nashville, TN USA. [Gray, Robert] Dana Farber Canc Inst, Ctr Stat, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. [Schiller, Joan H.] Univ Texas SW, Dallas, TX 75390 USA. RP Dowlati, A (reprint author), Univ Hosp Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44016 USA. EM afshin.dowlati@case.edu RI Johnson, David/A-7437-2009 FU NCI NIH HHS [5K23 CA109348-01, K23 CA109348] NR 28 TC 177 Z9 190 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2008 VL 14 IS 5 BP 1407 EP 1412 DI 10.1158/1078-0432.CCR-07-1154 PG 6 WC Oncology SC Oncology GA 268FR UT WOS:000253565000020 PM 18316562 ER PT J AU Attar, EC De Angelo, DJ Supko, JG D'Amato, F Zahrieh, D Sirulnik, A Wadleigh, M Ballen, KK McAfee, S Miller, KB Levine, J Galinsky, I Trehu, EG Schenkein, D Neuberg, D Stone, RM Amrein, PC AF Attar, Eyal C. De Angelo, Daniel J. Supko, Jeffrey G. D'Amato, Ferdinando Zahrieh, David Sirulnik, Andres Wadleigh, Martha Ballen, Karen K. McAfee, Steve Miller, Kenneth B. Levine, James Galinsky, Ilene Trehu, Elizabeth G. Schenkein, David Neuberg, Donna Stone, Richard M. Amrein, Philip C. TI Phase I and pharmacokinetic study of bortezomib in combination with idarubicin and cytarabine in patients with acute myelogenous leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEASOME INHIBITOR BORTEZOMIB; ACUTE MYELOID-LEUKEMIA; FACTOR-KAPPA-B; MULTIPLE-MYELOMA; STEM-CELLS; PEDIATRIC-PATIENTS; INVARIANT CHAIN; SOLID TUMORS; CANCER; METABOLISM AB Purpose: Proteasome inhibition results in cytotoxicity to the leukemia stem cell in vitro. We conducted this phase I study to determine if the proteasome inhibitor bortezomib could be safely added to induction chemotherapy in patients with acute myelogenous leukemia (AML). Experimental Design: Bortezomib was given on days 1, 4, 8, and 11 at doses of 0.7,1.0, 1.3, or 1.5 mg/m(2) with idarubicin 12 mg/m(2) on days 1 to 3 and cytarabine 100 mg/m(2)/day on days 1 to 7. Results: A total of 31 patients were enrolled. The median age was 62 years, and 16 patients were male. Nine patients had relapsed AML (ages, 18-59 years, n = 4 and >= 60 years, n = 5). There were 22 patients of >= 60 years with previously untreated AML (eight with prior myelodysplasia/ myeloproliferative disorder or cytotoxic therapy). All doses of bortezomib, up to and including 1.5 mg/m2, were tolerable. Nonhematologic grade 3 or greater toxicities included 12 hypoxia (38%; 11 were grade 3), 4 hyperbilirubinemia (13%), and 6 elevated aspartate aminotransferase (19%). Overall, 19 patients (61%) achieved complete remission (CR) and three had CR with incomplete platelet recovery. Pharmacokinetic studies revealed that the total body clearance of bortezomib decreased significantly (P < 0.01, N = 26) between the first (mean +/- SD, 41.9 +/- 17.1L/h/m(2)) and third (18.4 +/- 7.0 L/h/m(2)) doses. Increased bone marrow expression of CD74 was associated with CR. Conclusions: The combination of bortezomib, idarubicin, and cytarabine showed a good safety profile. The recommended dose of bortezomib for phase II studies with idarubicin and cytarabine is 1.5 mg/m(2). C1 [Attar, Eyal C.; Supko, Jeffrey G.; D'Amato, Ferdinando; Ballen, Karen K.; McAfee, Steve; Amrein, Philip C.] Massachusetts Gen Hosp, Ctr Canc, Ctr Leukemia, Hematol Oncol Unit, Boston, MA 02114 USA. [De Angelo, Daniel J.; Sirulnik, Andres; Wadleigh, Martha; Galinsky, Ilene; Stone, Richard M.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Zahrieh, David; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Miller, Kenneth B.; Levine, James] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Trehu, Elizabeth G.; Schenkein, David] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Leukemia, Hematol Oncol Unit, 32 Fruit St,Yawkey 7, Boston, MA 02114 USA. EM eattar@partners.org FU NCI NIH HHS [P01 CA066996] NR 49 TC 74 Z9 83 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 MAR 1 PY 2008 VL 14 IS 5 BP 1446 EP 1454 DI 10.1158/1078-0432.CCR-07-4626 PG 9 WC Oncology SC Oncology GA 268FR UT WOS:000253565000026 PM 18316568 ER PT J AU Fernando, NT Koch, M Rothrock, C Gollogly, LK D'Amore, PA Ryeom, S Yoon, SS AF Fernando, Namali T. Koch, Moritz Rothrock, Courtney Gollogly, Lila K. D'Amore, Patricia A. Ryeom, Sandra Yoon, Sam S. TI Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; COLORECTAL-CANCER; THERAPY; THROMBOSPONDIN-1; ENDOSTATIN; METASTASIS; EXPRESSION; RESISTANCE AB Purpose: Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis. We examined the mechanisms by which tumor cells may bypass the antiangiogenic effects of these endogenous regulators. Experimental Design: CT26 colon and RenCa renal carcinoma cells were stably transfected with Tsp1, endostatin, or tumstatin cDNA. Subcutaneous and metastatic tumor growth in syngeneic mice was analyzed. Expression of proangiogenic factors in resulting tumors was measured by quantitative real-time PCR. The combination of Tsp1 and vascular endothelial growth factor (VEGF) receptor-2 inhibition was also examined. Results: There was significant suppression of angiogenesis in flank tumors and liver metastases formed from cells overexpressing Tsp1, endostatin, or tumstatin. However, all tumors ultimately escaped angiogenesis inhibition. The combination of all three angiogenesis inhibitors had no additive effect beyond overexpression of a single inhibitor. Using quantitative real-time PCR, we found that VEGF and platelet-derived growth factor (PDGF) -A levels were routinely up-regulated at least 5-fold in all CT26 tumors overexpressing any antiangiogenic protein, and there were variable increases in angiopoietin 2 (Ang2), basic fibroblast growth factor, and PDGF-B. In contrast, RenCa tumors, which have high baseline levels of VEGF and PDGF-B, relied on basic fibroblast growth factor, Ang1, and PDGF-A up-regulation to counteract Tsp1 overexpression. Growth of CT26 cells with Tsp1 overexpression was suppressed when anti-VEGFR-2 treatment was added. Conclusions: Cancer cells with overexpression of three different endogenous angiogenesis inhibitor eventually escape angiogenesis inhibition by up-regulation of various proangiogenic factors. Tsp1, endostatin, and tumstatin may be functionally redundant in this system. These endogenous angiogenesis inhibitors are likely best used in combination with the blockade of proangiogenic pathways or with traditional chemotherapy or radiation therapy. C1 [Fernando, Namali T.; Koch, Moritz; Rothrock, Courtney; Gollogly, Lila K.; Yoon, Sam S.] Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. [Fernando, Namali T.; Koch, Moritz; Rothrock, Courtney; Gollogly, Lila K.; D'Amore, Patricia A.; Ryeom, Sandra; Yoon, Sam S.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Fernando, Namali T.; Koch, Moritz; Rothrock, Courtney; Gollogly, Lila K.; D'Amore, Patricia A.; Ryeom, Sandra; Yoon, Sam S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Fernando, Namali T.; Koch, Moritz; Rothrock, Courtney; Gollogly, Lila K.; D'Amore, Patricia A.; Ryeom, Sandra; Yoon, Sam S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ryeom, Sandra] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Ryeom, Sandra] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Yawkey 7B-7926,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org FU NCI NIH HHS [5 K12 CA 87723-03, 1 R21 CA117129-01] NR 32 TC 94 Z9 99 U1 0 U2 4 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 MAR 1 PY 2008 VL 14 IS 5 BP 1529 EP 1539 DI 10.1158/1078-0432.CCR-07-4126 PG 11 WC Oncology SC Oncology GA 268FR UT WOS:000253565000036 PM 18316578 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI Clinical considerations with the use of antiplatelet therapy in patients undergoing percutaneous coronary intervention SO CLINICAL CARDIOLOGY LA English DT Article DE catheterization/diagnostic interventional < cardiac; platelets; thrombosis/hypercoagulable states; acute coronary syndromes < ischemic heart disease; myocardial infarction < ischemic heart disease ID ELUTING STENT IMPLANTATION; TYPE-2 DIABETES-MELLITUS; ARTERY-DISEASE; PREMATURE DISCONTINUATION; PLATELET ACTIVATION; CLEAR PLATELETS; MG CLOPIDOGREL; RISK-FACTORS; THROMBOSIS; TRIAL AB Despite the proven benefits of using antiplatetet therapy in patients undergoing percutaneous coronary intervention (PCI), a number of key questions remain to be answered. In recent years, clopidogrel dosing strategies among such patients have evolved considerably, with newer approaches involving loading doses prior to PCI and increases in the time interval and loading dosage in an effort to overcome variable responsiveness/hyporesponsiveness to platelet inhibition. Further, the rote of glycoprotein (GP) IIb/IIIa antagonists in elective stenting continues to be defined, with recent evidence suggesting that most appropriate use of these agents is in high-risk patients with elevated troponin levels. There appears to be a relationship between the use of GP IIb/IIIa antagonists with clopidogrel loading and attenuation of early inflammatory and cardiac marker release. Strategies to minimize the chance of late stent thrombosis in patients who receive drug-eluting stents (DES) are also under intense investigation. Among some patients receiving sirolimus and paclitaxel DES, current standard long-term antiplatelet strategies may be insufficient. Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences. C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, TIMi Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Sch Med, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, TIMi Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Sch Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 29 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I28 EP I35 DI 10.1002/clc.20359 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400006 PM 18481820 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI Antiplatetet strategies: Evaluating their current role in the setting of acute coronary syndromes SO CLINICAL CARDIOLOGY LA English DT Article DE catheterization/diagnostic interventionat > cardiac; acute coronary syndromes > ischernic heart disease; platelets; thrombosis/hypercoaguable ID ST-SEGMENT ELEVATION; GLYCOPROTEIN IIB/IIIA INHIBITORS; PLACEBO-CONTROLLED TRIAL; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; RANDOMIZED-TRIAL; CLOPIDOGREL PRETREATMENT; CLINICAL-TRIAL; INTERVENTION; ABCIXIMAB AB Numerous clinical trials have established the value of antiplatelet therapies for acute coronary syndromes (ACS). Aspirin (ASA), thienopyridines (i.e., clopidogrel and ticlopidine) and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS and for the prevention of thrombotic complications of percutaneous coronary intervention (PCI). Clopidogrel is beneficial when administered before and after PCI, and is more effective when combined with either ASA or GP IIb/IIIa inhibitors in preventing post-PCI complications, coronary subacute stent thrombosis, and thrombotic events in general. It is currently unclear whether a higher loading dose of clopidogrel (600 mg) is better than the standard loading dose (300 mg), how tong therapy should continue, and which maintenance dose is optimal. The role of the GP IIb/IIIa antagonists in ACS is less clear due to conflicting data from several studies with different patient populations. Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high-risk ACS patients scheduled to undergo PCI, who demonstrate non-ST-segment elevation myocardial infarction and elevated troponin levels. C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 28 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I2 EP I9 DI 10.1002/clc.20362 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400002 PM 18481818 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI Investigating the mechanisms of hyporesponse to antiplatelet approaches SO CLINICAL CARDIOLOGY LA English DT Article DE catheterization/diagnostic interventional < cardiac; platelets; acute coronary syndromes < ischemic heart disease; myocardial infarction < ischemic heart disease; thrombosis/hypercoagulable states ID PERCUTANEOUS CORONARY INTERVENTION; TYPE-2 DIABETES-MELLITUS; ST-SEGMENT ELEVATION; ACUTE MYOCARDIAL-INFARCTION; PLATELET REACTIVITY; CLOPIDOGREL RESISTANCE; ASPIRIN RESISTANCE; ADENOSINE-DIPHOSPHATE; STENT IMPLANTATION; CONTROLLED TRIAL AB Hyporesponsiveness, or resistance, to antiplatelet therapy may be a major contributor to poorer outcomes among cardiac patients and may be attributed to an array of mechanisms - both modifiable and unmodifiable. Recent evidence has uncovered clinical, cellular, and genetic factors associated with hyporesponsiveness, Patients with severe acute coronary syndromes (ACS), type 2 diabetes, and increased body mass index appear to be the most at risk for hyporesponsiveness. Addressing modifiable mechanisms may offset hyporesponsiveness, while recognizing unmodifiable mechanisms, such as genetic polymorphisms and diseases that affect response to antiplatelet therapy, may help identify patients who are more likely to be hyporesponsive. Hyporesponsive patients might benefit from different dosing strategies or additional antiplatelet therapies. Trials correlating platelet function test results to clinical outcomes are required. Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness. C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Med Sch, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Med Sch, 3050 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 41 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I21 EP I27 DI 10.1002/clc.20360 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400005 PM 18481819 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI The problem of persistent platelet activation in acute coronary syndromes and following percutaneous coronary intervention SO CLINICAL CARDIOLOGY LA English DT Article DE catheterization/diagnostic intervention < cardiac; cardiovasular; acute coronary syndromes < ischemic heart disease; myocardial infarction < ischemic heart disease; platelets; thrombosis/hypercoagulable states ID STENT THROMBOSIS; REACTIVITY AB Platelets play a central role in the atherosclerotic inflammatory response, thrombotic vascular occlusion, microembolization, vasoconstriction, and plaque progression. Persistent platelet activation poses a serious problem among patients with acute coronary syndromes (ACS) and those who have undergone percutaneous coronary intervention (PCI), placing them at risk for ischemic events and subacute stent thrombosis. Patients undergoing PCI are at risk for further ischemic events because of procedure-related platelet activation as well as the inherent persistent platelet hyperreactivity and enhanced thrombin generation associated with ACS. Persistent platelet activation following an acute coronary event and/or PCI supports incorporating antiplatelet strategies into the standard medical management of such patients. In this clinical setting, antiplatelet therapies are capable of improving outcomes. Aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors, the 3 major pharmacologic approaches to persistent platelet activation, target various levels of the hemostatic pathways and thrombus formation. C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwaid@partners.org NR 17 TC 9 Z9 9 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I17 EP I20 DI 10.1002/clc.20363 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400004 PM 18481817 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Hatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Hatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI Assessing the current role of platelet function testing SO CLINICAL CARDIOLOGY LA English DT Article DE catheterization/diagnostic interventional < cardiac; acute coronary syndromes < ischemic heart disease; platelets; thrombosis/hypercoagulable states ID DRUG-ELUTING STENTS; ASPIRIN RESISTANCE; CARDIOVASCULAR-DISEASE; CLOPIDOGREL RESISTANCE; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; THROMBOSIS; EVENTS; RISK AB In vitro platelet function tests are commonly applied in research and offer justification for using antiplatelet therapy. However, studies assessing the ability of standardized platelet function tests to predict patients' clinical response to aspirin or clopidogrel have generated contradictory results. At this time, there is no standardized definition for resistance to antiplatelet therapy, and the appropriate treatment of patients who are hyporesponsive to these agents is not known. Although such tests have a role in research, their place in guiding therapy remains to be established, and prospective trials are urgently needed. The ideal platelet function test for clinical practice would be rapid, easy-to-use, inexpensive, and reliable. C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Hatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 24 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I10 EP I16 DI 10.1002/clc.20361 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400003 PM 18481816 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Michelson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Michelson, Alan D. Peterson, Eric Wiviott, Stephen TI Antiplatelet therapy and platelet function testing SO CLINICAL CARDIOLOGY LA English DT Editorial Material C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Med Sch, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Dept Med, Sinai Hosp, Sch Med, Baltimore, MD USA. [Michelson, Alan D.] Univ Massachusetts, Ctr Platelet Funct Studies, Sch Med, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp,Dept Med,Med Sch, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwaid@partners.org NR 1 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I36 EP I36 DI 10.1002/clc.20371 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400007 PM 18481821 ER PT J AU Braunwald, E Angiolillo, D Bates, E Berger, PB Bhatt, D Cannon, CP Furman, MI Gurbel, P Micheson, AD Peterson, E Wiviott, S AF Braunwald, Eugene Angiolillo, Dominick Bates, Eric Berger, Peter B. Bhatt, Deepak Cannon, Christopher P. Furman, Mark I. Gurbel, Paul Micheson, Alan D. Peterson, Eric Wiviott, Stephen TI Antiplatelet therapy and platelet function testing SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; ARTERY DISEASE; MECHANISMS; PATHOGENESIS C1 [Braunwald, Eugene; Cannon, Christopher P.; Wiviott, Stephen] Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Angiolillo, Dominick] Univ Florida, Coll Med, Dept Internal Med, Jacksonville, FL USA. [Bates, Eric; Peterson, Eric] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Berger, Peter B.] Geisinger Ctr Hlth Res, Danville, PA USA. [Bhatt, Deepak] Cardiovasc Coordinat Ctr, Dept Cardiovasc Med, Cleveland Clin, Cleveland, OH USA. [Furman, Mark I.] S Shore Hosp, South Weymouth, MA USA. [Gurbel, Paul] Johns Hopkins Univ, Sch Med, Dept Med, Sinai Hosp, Baltimore, MD USA. [Micheson, Alan D.] Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Worcester, MA 01605 USA. [Peterson, Eric] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Dept Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 4 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2008 VL 31 IS 3 SU 1 BP I1 EP I1 DI 10.1002/clc.20370 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278JJ UT WOS:000254281400001 PM 18481815 ER PT J AU Yachimski, P Puricelli, WP Nishioka, NS AF Yachimski, Patrick Puricelli, William P. Nishioka, Norman S. TI Patient predictors of esophageal stricture development after photodynamic therapy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract ID HIGH-GRADE DYSPLASIA; ENDOSCOPIC MUCOSAL RESECTION; BARRETTS-ESOPHAGUS; RADIOFREQUENCY ABLATION; 5-AMINOLEVULINIC ACID; EARLY CANCER; FOLLOW-UP; ADENOCARCINOMA; EFFICACY; TRIAL AB Background & Aims: The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barrett's esophagus, are associated with post-PDT stricturing. Methods: Data from all patients who had undergone PDT with porfimer sodium for Barrett's esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed. Results: One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007) There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barrett's esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P =.025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barrett's esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. Conclusions: An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barrett's esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT. C1 [Yachimski, Patrick] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Yachimski, P (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02115 USA. EM pyachimski@partners.org NR 29 TC 26 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2008 VL 6 IS 3 BP 302 EP 308 DI 10.1016/j.cgh.2007.12.001 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 273VX UT WOS:000253961100010 PM 18255349 ER PT J AU Stoffel, EM Ford, B Mercado, RC Punglia, D Kohlmann, W Conrad, P Blanco, A Shannon, KM Powell, M Gruber, SB Terdiman, J Chung, DC Syngal, S AF Stoffel, Elena M. Ford, Beth Mercado, Rowena C. Punglia, Darashana Kohlmann, Wendy Conrad, Peggy Blanco, Amie Shannon, Kristen M. Powell, Mark Gruber, Stephen B. Terdiman, Jonathan Chung, Daniel C. Syngal, Sapna TI Sharing genetic test results in Lynch syndrome: Communication with close and distant relatives SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID COLORECTAL-CANCER; 1ST-DEGREE RELATIVES; FOLLOW-UP; HNPCC AB Background & Aims: Clinical genetic testing can help direct cancer screening for members of Lynch syndrome families; however, there is limited information about family communication of genetic test results. Methods: A total of 174 probands who had genetic testing for Lynch syndrome were enrolled through 4 US cancer genetics clinics. Subjects were asked whether they had disclosed their genetic test results to first-, second-, and third-degree relatives. Univariate and multivariate analyses were used to identify clinical and demographic factors associated with informing immediate and extended family of genetic test results. Results: One hundred seventy-one of 174 probands (98%; 95% confidence interval, 95%-100%) reported that they had disclosed their genetic test result to a first-degree relative. Communication of test results to other relatives occurred significantly less often, with only 109 of 162 (67%; 95% confidence interval, 59%-74%) subjects with second- or third-degree relatives sharing their results. Individuals with a pathogenic mutation were significantly more likely to inform distant relatives than were subjects with a negative or indeterminate test result (odds ratio, 2.49; 95% confidence interval, 1.14-5.40). Probands' age, sex, and cancer status did not influence communication of genetic test results. Lack of closeness and concerns that relatives would worry or not understand the implications of test results were the primary reasons for not sharing genetic test results. Conclusions: Most individuals who undergo genetic testing for Lynch syndrome share their test results with first-degree family members; however, these results reach more distant relatives significantly less often. Interventions to improve communication of genetic test results to members of the extended family are necessary to provide optimal cancer prevention care to at-risk families. C1 [Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Powell, Mark] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Stoffel, Elena M.; Ford, Beth; Mercado, Rowena C.; Punglia, Darashana; Syngal, Sapna] Dana Faber Canc Inst, Div Populat Sci, Boston, MA USA. [Stoffel, Elena M.; Chung, Daniel C.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Kohlmann, Wendy; Gruber, Stephen B.] Univ Michigan, Med Ctr, Canc Genet Clin, Ann Arbor, MI USA. [Conrad, Peggy; Blanco, Amie; Terdiman, Jonathan] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Shannon, Kristen M.; Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc Risk Analysis, Boston, MA 02114 USA. RP Stoffel, EM (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM estoffel@partners.org OI Blanco, Amie/0000-0003-3690-0038 FU NCI NIH HHS [K24 CA113433-02, K07 CA 120448-01, K07 CA120448, K24 NCI CA 113433, K07 CA120448-01A1, K24 CA113433] NR 13 TC 36 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2008 VL 6 IS 3 BP 333 EP 338 DI 10.1016/j.cgh.2007.12.014 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 273VX UT WOS:000253961100015 PM 18258490 ER PT J AU Choueiri, TK AF Choueiri, Toni K. TI Factors associated with outcome in patients with advanced renal cell carcinoma in the era of Antiangiogenic agents SO CLINICAL GENITOURINARY CANCER LA English DT Review DE carbonic anhydrase IX; hypoxia-inducible factor; sunitinib; vascular endothelial growth factor; von hippel-lindau ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CARBONIC-ANHYDRASE-IX; LONG-TERM SURVIVAL; PROGNOSTIC-FACTORS; INTERFERON-ALPHA; FACTOR-RECEPTOR; MAMMALIAN TARGET; PHASE-II; CANCER AB Known clinical factors associated with outcome in advanced renal cell carcinoma (RCC) include performance status, disease-free interval, number of metastatic sites, and several laboratory variables such as hemoglobin, calcium, and lactate dehydrogenase. These factors were pertinent to the era of immunotherapy. Recent analysis from trials with anti-VEGF agents shows these factors continue to be of major importance. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau (VHL) pathway, are currently being investigated. Responses to VEGF-targeted agents seem to be related to a greater modulation of serum VEGF and soluble VEGF receptors levels. The impact of VHL gene status on clinical objective response to VEGF-targeted therapy was tested in a large study but was not found to predict a higher response rate to these agents. However, subsets of VHL mutations that predict a truncation of the VHL protein seem to have the best responses to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in patients with metastatic clear-cell RCC treated with novel antiangiogenic agents. These models, if externally and prospectively validated, will rationally select patients for specific VEGF-directed therapeutic agents. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, 44 Binney St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 62 TC 6 Z9 6 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2008 VL 6 IS 1 BP 15 EP 20 DI 10.3816/CGC.2008.n.002 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 291FR UT WOS:000255179600002 PM 18501077 ER PT J AU Higano, CS Quick, DP Bushnell, D Sartor, O AF Higano, Celestia S. Quick, Donald P. Bushnell, David Sartor, Oliver TI Safety analysis of repeated high doses of samarium-153 lexidronam in men with hormone-naive prostate cancer metastatic to bone SO CLINICAL GENITOURINARY CANCER LA English DT Article DE bone metastases; palliation; radiopharmaceuticals ID PHASE-II TRIAL; TARGETED THERAPY; CARCINOMA AB Purpose: The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (Sm-153-EDTIVIP) were investigated in men with hormone-naive prostate cancer metastatic to bone. Patients and Methods: Within 30 days of initiating androgen deprivation, the first of 4 planned doses of Sm-153-EDTIVIP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received Sm-153-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses. Results: There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received Sm-153-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of Sm-153-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of Sm-153-EDTMP There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities. Conclusion: In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repreated doses of Sm-153-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses. C1 [Higano, Celestia S.] Univ Washington, Med Ctr, Div Med Oncol, Seattle, WA 98109 USA. [Quick, Donald P.] Joe Arrington Canc Res & Treatment Ctr, Lubbock, TX USA. [Bushnell, David] VA Med Ctr, Dept Nucl Med, Iowa City, IA USA. [Sartor, Oliver] Louisiana State Univ, Med Ctr, Dept Med, Shreveport, LA 71130 USA. [Sartor, Oliver] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Higano, CS (reprint author), Univ Washington, Med Ctr, Div Med Oncol, 825 Eastlake Ave E, Seattle, WA 98109 USA. EM thigano@u.washington.edu NR 12 TC 6 Z9 6 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2008 VL 6 IS 1 BP 40 EP 45 DI 10.3816/CGC.2008.n.007 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 291FR UT WOS:000255179600007 PM 18501082 ER PT J AU Watnick, S Stooksbury, M Winter, R Riscoe, M Cohen, DM AF Watnick, Suzanne Stooksbury, Michael Winter, Rolf Riscoe, Michael Cohen, David M. TI White thrombus formation in blood tubing lines in a chronic hemodialysis unit SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; PARTICULATE MATTER; EPOETIN; ANEMIA AB Background and objectives: Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Results: Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Conclusions: Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted. C1 [Watnick, Suzanne; Cohen, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Winter, Rolf; Riscoe, Michael] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Watnick, Suzanne; Stooksbury, Michael; Cohen, David M.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. RP Watnick, S (reprint author), PVAMC, Dialysis Unit, P3 NEPH,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 12 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 IS 2 BP 382 EP 386 DI 10.2215/CJN.03540807 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 270GS UT WOS:000253709800012 PM 18184880 ER PT J AU Mittalhenkle, A Stehman-Breen, CO Shlipak, MG Fried, LF Katz, R Young, BA Seliger, S Gillen, D Newman, AB Psaty, BM Siscovick, D AF Mittalhenkle, Anuja Stehman-Breen, Catherine O. Shlipak, Michael G. Fried, Linda F. Katz, Ronit Young, Bessie A. Seliger, Stephen Gillen, Daniel Newman, Anne B. Psaty, Bruce M. Siscovick, David TI Cardiovascular risk factors and incident acute renal failure in older adults: The cardiovascular health study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID C-REACTIVE PROTEIN; ACUTE KIDNEY INJURY; INFLAMMATION; CLASSIFICATION; INSUFFICIENCY; MULTICENTER; VALIDATION; MORTALITY; DIALYSIS; THERAPY AB Background and objectives: Although the elderly are at increased risk for acute renal failure, few prospective studies have identified risk factors for acute renal failure in the elderly. Design, setting, participants, & measurements: The associations of cardiovascular disease risk factors, subclinical cardiovascular disease, and clinical coronary heart disease with the risk for development of acute renal failure were examined in older adults in the Cardiovascular Health Study, a prospective cohort study of community-dwelling older adults. Incident hospitalized cases of acute renal failure were identified through hospital discharge International Classification of Diseases, Ninth Revision codes and confirmed through physician diagnoses of acute renal failure in discharge summaries. Results: Acute renal failure developed in 225 (3.9%) of the 5731 patients during a median follow-up period of 10.2 yr. In multivariate analyses, diabetes, current smoking, hypertension, C-reactive protein, and fibrinogen were associated with acute renal failure. Prevalent coronary heart disease was associated with incident acute renal failure, and among patients without prevalent coronary heart disease, subclinical vascular disease measures were also associated with acute renal failure: Low ankle-arm index (<= 0.9), common carotid intima-media thickness, and internal carotid intima-media thickness. Conclusions: In this large, population-based, prospective cohort study, cardiovascular risk factors and both subclinical and clinical vascular disease were associated with incident acute renal failure in the elderly. C1 [Mittalhenkle, Anuja; Seliger, Stephen] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Stehman-Breen, Catherine O.; Psaty, Bruce M.; Siscovick, David] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Katz, Ronit; Gillen, Daniel] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Young, Bessie A.; Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Stehman-Breen, Catherine O.] Amgen Inc, Thousand Oaks, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Vet Adm Med Ctr, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne B.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Mittalhenkle, A (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Mail Code MQ360,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mittalhe@ohsu.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85083, N01 HC015103, N01 HC035129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01HC85079, N01HC85086, R01 HL073208]; NIDDK NIH HHS [DK07721, T32 DK007721] NR 31 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 IS 2 BP 450 EP 456 DI 10.2215/CJN.02610607 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 270GS UT WOS:000253709800022 PM 18256380 ER PT J AU Chen, R Cros, D Curra, A Di Lazzaro, V Lefaucheur, JP Magistris, MR Mills, K Roesler, KM Triggs, WJ Ugawa, Y Ziemann, U AF Chen, Robert Cros, Didier Curra, Antonio Di Lazzaro, Vincenzo Lefaucheur, Jean-Pascal Magistris, Michel R. Mills, Kerry Roesler, Kai M. Triggs, William J. Ugawa, Yoshikazu Ziemann, Ulf TI The clinical diagnostic utility of transcranial magnetic stimulation: Report of an IFCN committee SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE transcranial magnetic stimulation; electrophysiology; diagnosis; motor-evoked potentials; neurological disorders ID HUMAN MOTOR CORTEX; AMYOTROPHIC-LATERAL-SCLEROSIS; CORTICAL SILENT PERIOD; PROGRESSIVE MULTIPLE-SCLEROSIS; CERVICAL SPONDYLOTIC MYELOPATHY; SPINOCEREBELLAR ATAXIA TYPE-2; FOCAL HAND DYSTONIA; I-WAVE INTERACTION; LATENCY INTRACORTICAL INHIBITION; SOMATOSENSORY-EVOKED POTENTIALS AB The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer's disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Chen, Robert] Univ Toronto, Toronto Western Hosp, Toronto Western Res Inst, Div Neurol, Toronto, ON M5T 2S8, Canada. [Cros, Didier] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Curra, Antonio] Univ Rome La Sapienza Polo Pontino, LT, Osped A Fiorini Terracina, Dept Neurol Sci, Rome, Italy. [Di Lazzaro, Vincenzo] Univ Cattolica, Ist Neurol, Rome, Italy. [Lefaucheur, Jean-Pascal] Hop Henri Mondor, Serv Physiol Explorat Fonct, F-94010 Creteil, France. [Magistris, Michel R.] Univ Hosp Geneva, Dept Clin Neurosci, Geneva, Switzerland. [Mills, Kerry] Kings Coll Hosp London, Dept Clin Neurophysiol, London, England. [Roesler, Kai M.] Univ Hosp Bern, Dept Neurol, CH-3010 Bern, Switzerland. [Triggs, William J.] Univ Florida, Dept Neurol, Gainesville, FL USA. [Ugawa, Yoshikazu] Univ Tokyo, Dept Neurol, Tokyo, Japan. [Ziemann, Ulf] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany. RP Chen, R (reprint author), Univ Toronto, Toronto Western Hosp, Toronto Western Res Inst, Div Neurol, 7MC411,399 Bathurst St, Toronto, ON M5T 2S8, Canada. EM robert.chen@uhn.on.ca RI Chen, Robert/B-3899-2009; OI Chen, Robert/0000-0002-8371-8629; Di Lazzaro, Vincenzo/0000-0002-9113-5925 NR 479 TC 245 Z9 252 U1 2 U2 26 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAR PY 2008 VL 119 IS 3 BP 504 EP 532 DI 10.1016/j.clinph.2007.10.014 PG 29 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 277ZN UT WOS:000254253300003 PM 18063409 ER PT J AU Carr, M Goudreau, K Gauthier, PA Mitchell, MG AF Carr, Marcia Goudreau, Kelly Gauthier, Paul Andre Mitchell, Mitzi G. TI CNS practice, education, and regulation: An international collaboration between Canada and the united states SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Carr, Marcia] Burnaby Hosp, Burnaby, BC, Canada. [Goudreau, Kelly] Portland VA Med Ctr, Portland, OR USA. [Gauthier, Paul Andre; Mitchell, Mitzi G.] York Univ, Toronto, ON M3J 2R7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2008 VL 22 IS 2 BP 90 EP 90 PG 1 WC Nursing SC Nursing GA 268FS UT WOS:000253565200014 ER PT J AU Banks, MA Butler, ND Morrison, D Rossi, KA AF Banks, Melanie A. Butler, Nichole D. Morrison, Dolores Rossi, Karen A. TI From CNS graduate to board-certified CNS: The road to certification SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Banks, Melanie A.; Butler, Nichole D.; Morrison, Dolores; Rossi, Karen A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2008 VL 22 IS 2 BP 93 EP 93 PG 1 WC Nursing SC Nursing GA 268FS UT WOS:000253565200025 ER PT J AU Elhassan, B Ozbaydar, M Higgins, LD Warner, JJP AF Elhassan, Bassem Ozbaydar, Mehmet Higgins, Lawrence D. Warner, Jon J. P. TI Glenoid reconstruction in revision shoulder arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PROSTHESIS; SURGERY AB Failed shoulder arthroplasty associated with glenoid bony deficiency is a difficult problem. Revision surgery is complex with unpredictable outcome. We asked whether revision shoulder arthroplasty with glenoid bone grafting could lead to good outcome. We retrospectively reviewed 21 patients who underwent glenoid bone grafting using corticocancellous bone grafting or impaction grafting using cancellous bone graft. Three patients underwent revision TSA, five patients hemiarthroplasty, 10 patients hemiarthroplasty with biologic resurfacing of the glenoid, and three patients revision to reverse TSA. The patients had minimum 25 months followup (average, 45 months; range, 25-92 months). All patients had improvement in their range of motion and the Constant-Murley score. Most improvement occurred in patients with glenoid reimplantation. Patients who underwent revision reverse TSA had improvement in shoulder flexion but decrease in external rotation motion. We conclude revision shoulder arthroplasty with glenoid bone grafting can produce good short-term outcome and glenoid component reinsertion should be attempted whenever possible. C1 [Elhassan, Bassem; Ozbaydar, Mehmet; Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Shoulder Surg, Harvard Shoulder Serv,Dept Orthoped Surg, Boston, MA 02114 USA. [Higgins, Lawrence D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Sports Med & Shoulder Serv, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Shoulder Surg, Harvard Shoulder Serv,Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA. EM JJPWarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 20 TC 18 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2008 VL 466 IS 3 BP 599 EP 607 DI 10.1007/s11999-007-0108-0 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 267EQ UT WOS:000253492700014 PM 18213509 ER PT J AU Becker, ML Aarnoudse, AL Newton-Cheh, C Hofman, A Uitterlinden, AG Visser, LE Stricker, BH AF Becker, M. L. Aarnoudse, A. L. Newton-Cheh, C. Hofman, A. Uitterlinden, A. G. Visser, L. E. Stricker, B. H. TI Genetic variation in the nitric oxide synthase 1 adaptor protein gene is associated with reduced effectiveness of sulfonylurea drugs and with increased mortality. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Becker, M. L.; Aarnoudse, A. L.; Hofman, A.; Uitterlinden, A. G.; Visser, L. E.; Stricker, B. H.] Erasmus MC, Rotterdam, Netherlands. [Newton-Cheh, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Becker, Matthijs/A-6437-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S15 EP S16 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800047 ER PT J AU Schneeweiss, S Slomon, DH Korzenik, J Canning, C Bressler, B AF Schneeweiss, S. Slomon, D. H. Korzenik, J. Canning, C. Bressler, B. TI Infliximab use in patients with inflammatory bowel disease and the risk of serious bacterial infections. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Schneeweiss, S.; Slomon, D. H.; Canning, C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. [Korzenik, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bressler, B.] Univ Vancouver, Vancouver, BC, Canada. RI Schneeweiss, Sebastian/C-2125-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S43 EP S43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800137 ER PT J AU Marx, BP Forsyth, JP Gallup, GG Fuse, T Lexington, JM AF Marx, Brian P. Forsyth, John P. Gallup, Gordon G. Fuse, Tiffany Lexington, Jennifer M. TI Tonic immobility as an evolved predator defense: Implications for sexual assault survivors SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE freezing; PTSD; rape; rape-induced paralysis; sexual assault; tonic immobility; trauma ID POSTTRAUMATIC-STRESS-DISORDER; REFLEX ANIMAL HYPNOSIS; CHICKENS GALLUS-GALLUS; LEARNED HELPLESSNESS; DOMESTIC CHICKS; FEAR RESPONSE; BEHAVIORAL STRATEGIES; ANOLIS-CAROLINENSIS; PASSIVE-AVOIDANCE; JAPANESE-QUAIL AB This article reviews research concerning the possible relationship between tonic immobility (TI) and human reactions to sexual assault. This review includes a description of the characteristic features of TI and a discussion of the most widely accepted theoretical explanation for TI. The possibility that humans may exhibit TI is explored and conditions that might elicit TI in humans are identified. In particular, we focus on TI in the context of sexual assault, because this form of trauma often involves elements that are necessary for the induction of TI in nonhuman animals, namely, fear and perceived physical restraint. The important similarities and differences in how TI manifests in humans and nonhuman animals are highlighted, future research directions are offered, and clinical implications are suggested. C1 [Marx, Brian P.] VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Forsyth, John P.; Gallup, Gordon G.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [Lexington, Jennifer M.] Univ Massachusetts, Univ Hlth Serv, Amherst, MA 01003 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, Behav Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov NR 126 TC 76 Z9 76 U1 2 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD MAR PY 2008 VL 15 IS 1 BP 74 EP 90 DI 10.1111/j.1468-2850.2008.00112.x PG 17 WC Psychology, Clinical SC Psychology GA 263YE UT WOS:000253251600007 ER PT J AU Mendez, MF Shapira, JS AF Mendez, Mario F. Shapira, Jill S. TI The spectrum of recurrent thoughts and behaviors in frontotemporal dementia SO CNS SPECTRUMS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; FRONTAL-LOBE DEGENERATION; ALZHEIMERS-DISEASE; CLINICAL-FEATURES; SEMANTIC DEMENTIA; TEMPORAL VARIANT; PICKS-DISEASE; BRAIN-INJURY; SYMPTOMS; DIAGNOSIS AB This article describes the spectrum of recurrent thoughts and behaviors that can result from frontotemporal dementia (FTD) and its variants. Although repetitive behaviors can result from a range of brain disorders, FTD is the most common neurologic cause of new-onset recurrent thoughts and behaviors in middle or late life. Patients with FTD can manifest typical or bizarre compulsions, hoarding, verbal and motor stereotypies and complex tics; self-injurious acts, perseverations; and fixed, obsessional thoughts. The frequency and variability of these repetitive behaviors suggest a common disturbance of orbitofrontal-basal ganglia circuits involved in response inhibition. The amelioration of these recurrent events with the administration of serotonin selective reuptake inhibitors further suggests a serotonergic deficit. C1 [Mendez, Mario F.] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA 90073 USA. [Mendez, Mario F.; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), Vet Affairs Greater Los Angeles Healthcare, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu; jshapira@ucla.edu NR 67 TC 18 Z9 19 U1 1 U2 5 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2008 VL 13 IS 3 BP 202 EP 208 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 282KN UT WOS:000254566800009 PM 18323753 ER PT J AU Ali, S Welch, CA Park, LT Pliakas, AM Wilson, A Nicolson, S Huffman, J Fricchione, GL AF Ali, Sherese Welch, Charles A. Park, Lawrence T. Pliakas, Andrea M. Wilson, Amanda Nicolson, Stephen Huffman, Jeff Fricchione, Gregory L. TI Encephalitis and catatonia treated with ECT SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE encephalitis; malignant catatonia; electroconvulsive therapy ID LIMBIC ENCEPHALITIS; ELECTROCONVULSIVE-THERAPY; MALIGNANT CATATONIA; LETHARGICA; PATIENT; MRI AB Objective: To describe 2 cases of encephalitis with neuropsychiatric symptoms including catatonia, compounded by neuroleptic use for delirious agitation culminating in malignant catatonia responsive to electroconvulsive therapy (ECT). Background: Neuropsychiatric symptoms including catatonia can be manifestations of limbic encephalitis and encephalitides of unidentified etiology, including encephalitis lethargica. Catatonic features are often difficult to appraise in this context. This can easily lead to the use of neuroleptics, which may precipitate worsening of catatonia. Method: Medical, neurologic, and psychiatric histories, physical examination findings, results of laboratory, imaging and neurophysiologic investigations, and treatment response with medications and ECT were recorded. Results: Both patients showed significant improvement with ECT. Conclusions: Malignant catatonia can complicate encephalitis lethargica and idiopathic limbic encephalitis, which already carry high mortality rates. When neuroleptics are used for agitation in cases of encephalitis, physicians must be wary of precipitating malignant catatonia and neuroleptics should be discontinued when such a danger emerges. Although lorazepam is helpful in treating catatonia, it may not suffice, as in the cases presented. ECT deserves serious consideration early in the course of malignant catatonia and for catatonia nested in encephalopathy secondary to encephalitis, unresolved with lorazepam. C1 [Ali, Sherese] Toronto Western Hosp, Dept Neuropsychiat, Toronto, ON M5T 2S8, Canada. [Fricchione, Gregory L.] Div Psychiat & Med, Boston, MA USA. [Welch, Charles A.; Pliakas, Andrea M.; Wilson, Amanda; Nicolson, Stephen; Huffman, Jeff] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pliakas, Andrea M.] McLean Hosp, Boston, MA USA. [Welch, Charles A.; Park, Lawrence T.; Huffman, Jeff; Fricchione, Gregory L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ali, S (reprint author), Toronto Western Hosp, Dept Neuropsychiat, 7th Floor,Main Pavil,Room 430,399 Bathurst St, Toronto, ON M5T 2S8, Canada. EM sherese.ali@uhn.on.ca NR 28 TC 15 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD MAR PY 2008 VL 21 IS 1 BP 46 EP 51 PG 6 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 281NB UT WOS:000254503200010 PM 18327024 ER PT J AU Bordeianou, L Rockwood, T Baxter, N Lowry, A Mellgren, A Parker, S AF Bordeianou, L. Rockwood, T. Baxter, N. Lowry, A. Mellgren, A. Parker, S. TI Does incontinence severity correlate with quality of life? Prospective analysis of 502 consecutive patients SO COLORECTAL DISEASE LA English DT Article DE faecal incontinence; quality of life; severity of incontinence; FISI; FIQL ID FECAL INCONTINENCE; HEALTH SURVEY; IMPACT; COLOSTOMY; REPAIR; SF-36 AB Objective The Fecal Incontinence Severity Index (FISI) is widely used in the assessment of patients with faecal incontinence, but the relationship between FISI and the measurements of quality of life, such as the Fecal Incontinence Quality of Life Scale (FIQL) and the Medical Outcomes Survey (SF-36) has not been evaluated previously. The aim of the present study was to evaluate the relationship between disease severity and quality of life in a large cohort of patients. Method Five hundred and two consecutive patients (84.4% female, mean age 56 years) were evaluated for faecal incontinence between May 2004 and October 2005. Patients completed FISI, FIQL and SF-36 questionnaires. Pearson's coefficients were determined for the relationships between FISI and subscales of FIQL and SF-36. Quality of life scores were compared between groups of patients with different levels of incontinence severity (mild, moderate, severe) using Student's t-test. Results Sixty-eight per cent of patients were incontinent of solid stool, 62% of liquid stool, and 90% of gas or mucus. The average FISI score was 36 (0-61). Moderate correlations were found between FISI and all subscales in FIQL (negative 0.29 to 0.41; P < 0.0001). Weak correlations were found between FISI and the social functioning (-0.21) and mental health (-0.17) scales in SF-36 (P < 0.05). Scores on the FIQL differed significantly between mild, moderate and severe incontinence. Conclusion FISI was only moderately correlated with a disease-specific quality of life measurement (FIQL). Even though this supports the common assumption that the quality of life in the patients with faecal incontinence worsens with an increase in disease severity, it also stresses the need of measuring both variables to determine the true impact of any treatment. C1 Univ Minnesota, Div Colon & Rectal Surg, St Paul, MN 55108 USA. [Bordeianou, L.; Lowry, A.; Mellgren, A.; Parker, S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bordeianou, L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rockwood, T.] Univ Minnesota, Hlth Policy & Management Sch Publ Hlth, St Paul, MN 55108 USA. [Baxter, N.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Baxter, N.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org RI Baxter, Nancy/E-7020-2015 OI Baxter, Nancy/0000-0003-4793-4620 NR 26 TC 43 Z9 45 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-8910 J9 COLORECTAL DIS JI Colorectal Dis. PD MAR PY 2008 VL 10 IS 3 BP 273 EP 279 DI 10.1111/j.1463-1318.2007.01288.x PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 258UW UT WOS:000252896000013 PM 17608751 ER PT J AU Yeung, A Fung, F Yu, SC Vorono, S Ly, M Wu, S Fava, M AF Yeung, Albert Fung, Freddy Yu, Shu-Ching Vorono, Sienna Ly, Mary Wu, Shirley Fava, Maurizio TI Validation of the Patient Health Questionnaire-9 for depression screening among chinese Americans SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PRIMARY-CARE; PHQ-9; PREVALENCE AB Objective: The objective of this study was to validate the Chinese Bilingual version of the Patient Health Questionnaire (CB-PHQ-9) for screening for depression among Chinese Americans in primary care. Method: Chinese-American patients attending a primary care clinic were screened for major depressive disorder (MDD) using the CB-PHQ-9. All patients who scored 15 or higher on the CB-PHQ-9 were interviewed using the Chinese-bilingual Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, patient version. Eight percent of patients who scored less than 15 on the CB-PHQ-9 were randomly selected and interviewed with the depression module of the Chinese-bilingual Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, patient version. Results: During the study, 1940 unduplicated patients completed the CB-PHQ-9. The CB-PHQ-9 had high internal consistency (alpha = 0.91), and the scores of each of its 9 items had moderate to moderately high correlations (0.52-0.85) with the total scores. The sensitivity and specificity of the CB-PHQ-9 for recognizing MDD were found to be 81% and 98%, respectively, and the area under the receiver operating characteristic curve was estimated to be 0.97 (SE, 0.01). Conclusion: The CB-PHQ-9 is a valid and useful instrument for screening for MDD among Chinese Americans in primary care. (c) 2008 Elsevier Inc. All rights reserved. C1 [Yeung, Albert; Fung, Freddy; Yu, Shu-Ching; Vorono, Sienna; Ly, Mary; Wu, Shirley; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Yeung, Albert] S Cove Community Hlth Ctr, Dept Behav Hlth, Boston, MA 02111 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. EM ayeung@partners.org FU NIMH NIH HHS [K23 MH067085, K23 MH067085-05, MH67085-01A1] NR 12 TC 51 Z9 51 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 2008 VL 49 IS 2 BP 211 EP 217 DI 10.1016/j.comppsych.2006.06.002 PG 7 WC Psychiatry SC Psychiatry GA 263RX UT WOS:000253235300016 PM 18243896 ER PT J AU Shepherd, R Macer, JL Grady, D AF Shepherd, Rodger Macer, Judith L. Grady, Deborah TI Planning for closeout - From Day One SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE clinical trials; closeout; contingency planning ID RANDOMIZED CONTROLLED TRIAL; ESTROGEN PLUS PROGESTIN; HEART-ATTACK TRIAL; POSTMENOPAUSAL WOMEN; OPERATIONAL ASPECTS; EARLY TERMINATION; CLINICAL-TRIALS; FOLLOW-UP; HYPERTENSION; OUTCOMES AB Clinical trials are often stopped prematurely by Data and Safety Monitoring Boards, sponsors, or the investigators for reasons such as unexpected harmful effects of the intervention, clear lack of benefit, or futility due to sluggish recruitment or an unexpectedly low outcome rate in the placebo group. Planning for closeout, however, usually does not begin until after the trial is well underway. This article describes the experience of the Heart and Estrogen/progestin Replacement Study (HERS) investigators when data from the first year of follow-up revealed a clear but non-significant divergence in outcome rates between the treatment groups, and planning for early closure was initiated. Three advantages of beginning early to plan for closeout are described and approaches to planning closeout are suggested. (C) 2007 Elsevier Inc. All rights reserved. C1 [Grady, Deborah] UCSF, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), UCSF, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 19 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 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2008 VL 29 IS 2 BP 136 EP 139 DI 10.1016/j.cct.2007.06.001 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 276BZ UT WOS:000254117600006 PM 17644047 ER PT J AU Caplan, D Chen, E Waters, G AF Caplan, David Chen, Evan Waters, Gloria TI Task-dependent and task-independent neurovascular responses to syntactic processing SO CORTEX LA English DT Article DE fMRI syntax; task effects ID EVENT-RELATED FMRI; SPOKEN-LANGUAGE COMPREHENSION; LEFT PREFRONTAL CORTEX; SURFACE-BASED ANALYSIS; SENTENCE COMPREHENSION; WORKING-MEMORY; BROCAS AREA; AMBIGUITY RESOLUTION; BRAIN ACTIVATION; RELATIVE CLAUSES AB The neural basis for syntactic processing was studied using event-related fMRI to determine the locations of BOLD signal increases in the contrast of syntactically complex sentences with center- embedded, object- extracted relative clauses and syntactically simple sentences with right-branching, subject- extracted relative clauses in a group of 15 participants in three tasks. In a sentence verification task, participants saw a target sentence in one of these two syntactic forms, followed by a probe in a simple active form, and determined whether the probe expressed a proposition in the target. In a plausibility judgment task, participants determined whether a sentence in one of these two syntactic forms was plausible or implausible. Finally, in a non-word detection task, participants determined whether a sentence in one of these two syntactic forms contained only real words or a non-word. BOLD signal associated with the syntactic contrast increased in the left posterior inferior frontal gyrus in non-word detection and in a widespread set of areas in the other two tasks. We conclude that the BOLD activity in the left posterior inferior frontal gyrus reflects syntactic processing independent of concurrent cognitive operations and the more widespread areas of activation reflect the use of strategies and the use of the products of syntactic processing to accomplish tasks. C1 [Caplan, David; Chen, Evan] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. [Chen, Evan] Massachusetts Gen Hosp, MGH MIT HMS, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Waters, Gloria] Boston Univ, Dept Speech Hearing & Language Sci, Boston, MA 02215 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD NIH HHS [DC02146, R01 DC002146, R01 DC002146-10A2, R01 DC002146-11] NR 65 TC 49 Z9 50 U1 3 U2 7 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAR PY 2008 VL 44 IS 3 BP 257 EP 275 DI 10.1016/j.cortex.2006.06.005 PG 19 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 276ON UT WOS:000254152000006 PM 18387556 ER PT J AU Sinuff, T Cook, DJ Keenan, SP Burns, KEA Adhikari, NKJ Rocker, GM Mehta, S Kacmarek, R Eva, K Hill, NS AF Sinuff, Tasnim Cook, Deborah J. Keenan, Sean P. Burns, Karen E. A. Adhikari, Neill K. J. Rocker, Graerne M. Mehta, Sangeeta Kacmarek, Robert Eva, Kevin Hill, Nicholas S. TI Noninvasive ventilation for acute respiratory failure near the end of life SO CRITICAL CARE MEDICINE LA English DT Article DE noninvasive ventilation; do not resuscitate; palliation; survey ID POSITIVE-PRESSURE VENTILATION; REFUSED ENDOTRACHEAL INTUBATION; OBSTRUCTIVE PULMONARY-DISEASE; PALLIATIVE CARE; EXACERBATION; MASK AB Rationale: For patients with acute respiratory failure who have declined intubation and resuscitation or have chosen comfort measures only, noninvasive ventilation (NIV) may help them achieve important health or personal goals, or merely prolong the dying process. Objective. To determine clinicians' attitudes to and stated use of NIV for these patients. Methods. We developed an instrument to assess the attitudes of intensivists, pulmonologists, and respiratory therapists (RTs) toward the use of NIV for patients with acute respiratory failure near or at the end of life. After assessing its psychometric properties, we mailed the survey to these clinicians at 18 Canadian and two U.S. hospitals. We analyzed factors associated with stated use of NIV for do-not-resuscitate and comfort-measures-only patients. Results: Overall, 104 of 183 (57%) physicians and 290 of 473 (61%) RTs participated. Two thirds of physicians include NIV during life support discussions with do-not-resuscitate patients at least sometimes, and 87% of RTs stated that NIV should be included in such discussions. For patients choosing comfort measures only, almost half of physicians reported including NIV as an option in their discussions at least sometimes, while fewer than half of RTs stated that these discussions should be conducted. Most (> 80%) physicians use NIV and most (> 80%) RTs are asked to initiate NIV for do-not-resuscitate patients with chronic obstructive pulmonary disease or cardiogenic pulmonary edema. Fewer clinicians report using NIV for do-not-resuscitate patients with underlying malignancy (59% of physicians, 69% of RTs) or for patients choosing comfort measures only (40% of physicians, 51% of RTs; p <.001). Conclusions: For patients with do-not-resuscitate orders, many physicians use NIV, and many RTs are asked to initiate NIV, most often to treat chronic obstructive pulmonary disease and cardiogenic pulmonary edema. Further study is needed on the goals of NIV near the end of life, whether these goals are understood by all stakeholders, and how well they are achieved in practice. C1 [Sinuff, Tasnim; Adhikari, Neill K. J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON, Canada. [Burns, Karen E. A.] Univ Toronto, Dept Crit Care, Toronto, ON, Canada. [Burns, Karen E. A.] Univ Toronto, St Michaels Hosp, Dept Crit Care, Toronto, ON M5B 1W8, Canada. [Burns, Karen E. A.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Burns, Karen E. A.] Univ Toronto, Keenan Res Ctr, Toronto, ON, Canada. [Sinuff, Tasnim; Burns, Karen E. A.; Adhikari, Neill K. J.; Mehta, Sangeeta] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Cook, Deborah J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Cook, Deborah J.; Eva, Kevin] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Keenan, Sean P.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Rocker, Graerne M.] Queen Elizabeth 2 Hlth Sci Ctr, Div Resp & Palliat Med, Halifax, NS, Canada. [Rocker, Graerne M.] Dalhousie Univ, Halifax, NS, Canada. [Kacmarek, Robert] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. [Kacmarek, Robert] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hill, Nicholas S.] Tufts Univ, New England Med Ctr, Sch Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02111 USA. RP Sinuff, T (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON, Canada. EM taz.sinuff@sunnybrook.ca RI Mehta, Sangeeta/C-4623-2015 NR 17 TC 27 Z9 28 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 MAR PY 2008 VL 36 IS 3 BP 789 EP 794 DI 10.1097/CCM.0B013E3181653584 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 266QD UT WOS:000253450500017 PM 18209669 ER PT J AU Fink, H Helming, M Unterbuchner, C Lenz, A Neff, F Martyn, JAJ Blobner, M AF Fink, Heidrun Helming, Marc Unterbuchner, Christoph Lenz, Andrea Neff, Frauke Martyn, J. A. Jeevendra Blobner, Manfred TI Systemic inflammatory response syndrome increases immobility-induced neuromuscular weakness SO CRITICAL CARE MEDICINE LA English DT Article DE critical illness; immobilization; inflammation; myopathy; muscle contraction; acetylcholine receptors ID CRITICAL ILLNESS MYOPATHY; CRITICALLY-ILL PATIENTS; SKELETAL-MUSCLE; ACETYLCHOLINE-RECEPTORS; D-TUBOCURARINE; INDUCED HYPERKALEMIA; RISK-FACTORS; RAT; MECHANISMS; DYSFUNCTION AB Objective: Inflammation and immobility are comorbid etiological factors inducing muscle weakness in critically ill patients. This study establishes a rat model to examine the effect of inflammation and immobilization alone and in combination on muscle contraction, histology, and acetylcholine receptor regulation. Design: Prospective, randomized, experimental study. Setting: Animal laboratory of a university hospital. Subjects: Sprague-Dawley rats. Interventions: To produce systemic inflammation, rats (n = 34) received three consecutive intravenous injections of Corynebactedum parvum on days 0, 4, and 8. Control rats (n = 21) received saline. Both groups were further divided to have one hind limb either immobilized by pinning of knee and ankle joints or sham-immobilized (surgical leg). The contralateral nonsurgical leg of each animal served as control (nonsurgical leg). Measurements and Main Results. After 12 days, body weight and muscle mass were significantly reduced in all C. parvum animals compared with saline-injected rats. Immobilization led to local muscle atrophy. Normalized to muscle mass, tetanic contraction was reduced in the surgical leg after immobilization (7.64 +/- 1.91 N/g) and after inflammation (8.71 +/- 2.0 N/g; both p < .05 vs. sham immobilization and saline injection, 11.03 +/- 2.26 N/g). Histology showed an increase in inflammatory cells in all C. parvum-injected animals. Immobilization in combination with C. parvum, injection had an additive effect on inflammation. Acetylcholine receptors were increased in immobilized muscles and in all muscles of C. parvum-injected animals. Conclusions. The muscle weakness in critically ill patients can be replicated in our novel rat model. Inflammation and immobilization independently lead to muscle weakness. C1 [Fink, Heidrun; Helming, Marc; Unterbuchner, Christoph; Blobner, Manfred] Tech Univ Munich, Klinikum Rechts Isar, Anasthesiol Klin, D-8000 Munich, Germany. [Lenz, Andrea] Tech Univ Munich, Klinikum Rechts Isar, Inst Expt Onkol & Therapieforsch, D-8000 Munich, Germany. [Neff, Frauke] Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol & Patholog Anat, D-8000 Munich, Germany. [Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Boston, MA USA. RP Fink, H (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Anasthesiol Klin, D-8000 Munich, Germany. EM h.fink@lrz.bim.de OI Lewald, Heidrun/0000-0002-5192-425X FU NIGMS NIH HHS [R01 GM055082, GM21500, GM31569]; PHS HHS [55082] NR 45 TC 29 Z9 29 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 MAR PY 2008 VL 36 IS 3 BP 910 EP 916 DI 10.1097/CCM.0B013E3181659669 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 266QD UT WOS:000253450500034 PM 18431280 ER PT J AU Schein, J Janagap-Benson, C Grant, R Sikirica, V Doshi, D Olson, W AF Schein, Jeff Janagap-Benson, Carmela Grant, Richard Sikirica, Vanja Doshi, Dilesh Olson, William TI A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article; Proceedings Paper CT 103rd International Conference of the American-Thoracic-Society CY MAY 18-23, 2007 CL San Francisco, CA SP Amer Thorac Soc DE community-acquired pneumonia; hospitalization; length of stay; levofloxacin; moxifloxacin ID PROPENSITY SCORE; ADMINISTRATIVE DATA; CARE; MANAGEMENT; OUTCOMES; COSTS; EPIDEMIOLOGY; GUIDELINES; ADULTS AB Objective: Length of stay (LOS) and hospitalization costs were compared among patients admitted for community-acquired pneumonia (CAP) and initially treated with either levofloxacin 750 mg intravenous (IV) or with moxifloxacin 400 mg IV. Hospital-related complications and relationship of LOS and comorbidities were descriptively examined. Methods:A retrospective database study was conducted of adult patients admitted for CAP and given levofloxacin 750 mg IV or moxifloxacin 400 mg IV through the first 3 days of hospitalization, using the Premier Perspective+ comparative database. Cohorts were matched 1:1 by hospital geographic location, by coarse caliper propensity scores using all baseline covariates, and by Mahalanobis metric matching based on age and severity (All Patient Refined-Diagnosis-related Groups Severity of Illness (APR-DRG SOI) index). Comparisons between groups were further adjusted for characteristics that remained imbalanced after matching using generalized estimating equation methodology. Results: The initial sample of 3868 patients (levofloxacin = 827; moxifloxacin = 3041) was reduced to 1594 (797 patients per treatment group) after matching. Analyses of matched cohorts showed that the mean hospital LOS was significantly shorter for patients treated with levofloxacin 750 mg IV than for those patients treated with moxifloxacin 400 mg IV (5.8 vs. 6.4 days, respectively; least squares mean difference = 0.54 days; p = 0.020). Hospitalization costs were also lower for the levofloxacin 750 mg IV-treated patients (least squares mean difference = US$129; p = 0.753). There were no significant differences in the percentage of patients experiencing complications. Limitations: Although claims databases provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure treatment groups are balanced with respect to patient and clinical characteristics. In addition, data may be missing or miscoded. Conclusions: This retrospective study suggests that among patients hospitalized with CAP, initial treatment with levofloxacin 750 mg IV is associated with a significantly shorter mean hospital LOS compared with treatment with moxifloxacin 400 mg IV. The clinical implications of a shorter hospital LOS include improved patient and economic outcomes. C1 [Schein, Jeff; Janagap-Benson, Carmela; Sikirica, Vanja; Doshi, Dilesh; Olson, William] Ortho McNeil Sci Affairs LLC, Raritan, NJ USA. [Grant, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Grant, Richard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Schein, J (reprint author), Ortho McNeil Sci Affairs LLC, Raritan, NJ USA. EM JSchein@OMJUS.JNJ.com OI Grant, Richard/0000-0002-6164-8025 NR 31 TC 21 Z9 23 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD MAR PY 2008 VL 24 IS 3 BP 895 EP 906 DI 10.1185/030079908X273408 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 279ZD UT WOS:000254393800029 PM 18419876 ER PT J AU Kutuk, O Letai, A AF Kutuk, Ozgur Letai, Anthony TI Regulation of Bcl-2 family proteins by posttranslational modifications SO CURRENT MOLECULAR MEDICINE LA English DT Review DE Bcl-2; apoptosis; BH3-only; BAX; BIM; BID; BAD; phosphorylation; kinase; proteosome; MCL-1 ID CYTOCHROME-C RELEASE; CISPLATIN-INDUCED APOPTOSIS; X-L DEAMIDATION; PROTEASOME-DEPENDENT DEGRADATION; DRUG-INDUCED APOPTOSIS; PROSTATE-CANCER CELLS; DNA-DAMAGE RESPONSE; NITRIC-OXIDE; SIGNALING PATHWAY; PROAPOPTOTIC FUNCTION AB Like many proteins, function and abundance of Bcl-2 family proteins are influenced by posttranslational modifications. These modifications include phosphorylation, proteolytic cleavage, ubiquitination, and proteosomal degradation. These modifications, depending on cellular context and the proteins involved, can result either in a promotion of inhibition of apoptosis. Many of these modifications are governed by the activity of enzymes. As modulation of enzymatic activity can be achieved fairly efficiently using small molecules, understanding the effects of posttranslational modifications may allow for the therapeutic inhibition or promotion of apoptosis. C1 [Kutuk, Ozgur; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu NR 153 TC 53 Z9 54 U1 2 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAR PY 2008 VL 8 IS 2 BP 102 EP 118 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 274RT UT WOS:000254019400004 PM 18336291 ER PT J AU Filippopoulos, T Rhee, DJ AF Filippopoulos, Theodoros Rhee, Douglas J. TI Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE ab interno trabeculectomy; Ex-PRESS shunt; glaucoma penetrating surgery; goniotomy; miniature glaucoma device; Trabectome ID OPEN-ANGLE GLAUCOMA; LASER SUTURE LYSIS; FLUOROURACIL FILTERING SURGERY; NONPENETRATING DEEP SCLERECTOMY; RANDOMIZED CLINICAL-TRIAL; IMPLANT EX-PRESS; FOLLOW-UP; SCLERAL FLAP; INTRAOCULAR-PRESSURE; DRAINAGE IMPLANT AB Penetrating glaucoma surgery will continue to evolve. As prospective randomized clinical trials become available, we will determine the exact role of these surgical techniques in the glaucoma surgical armamentarium. C1 [Filippopoulos, Theodoros; Rhee, Douglas J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Glaucoma Consultat Serv, Boston, MA 02048 USA. RP Rhee, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02048 USA. EM Douglas_Rhee@meei.harvard.edu NR 76 TC 20 Z9 20 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD MAR PY 2008 VL 19 IS 2 BP 149 EP 154 DI 10.1097/ICU.0b013e3282f4f49e PG 6 WC Ophthalmology SC Ophthalmology GA 267YT UT WOS:000253545800011 PM 18301289 ER PT J AU Schwab, P Klein, RF AF Schwab, Pascale Klein, Robert F. TI Nonpharmacological approaches to improve bone health and reduce osteoporosis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE bone health; exercise; osteoporosis; rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; FEMORAL-NECK FRACTURE; QUALITY-OF-LIFE; HIP FRACTURE; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; FOLLOW-UP; COMPRESSION FRACTURES; ELDERLY INDIVIDUALS; WEIGHT-BEARING AB Purpose of review With an aging population, osteoporosis has become a public health concern and an area of increased awareness among both patients and medical practitioners. Timely screening and pharmacologic treatment of low bone mass effectively reduces fracture risk. Nonpharmacologic interventions, however, deserve equal emphasis both in the prevention and treatment of osteoporosis. Recent findings Recent advances in bone biology have established that exercise in the form of short, repetitive mechanical loading leads to the greatest gains in bone strength. As demonstrated by both observational and randomized exercise intervention trials, these gains are best achieved in childhood but can be maintained in adulthood with continued regular weight-bearing exercise. In the later years, evidence supports the implementation of balance training to decrease fall risk, especially in elderly patients with low bone mass. Following an osteoporotic fracture, a multidisciplinary rehabilitation program with an emphasis on early mobilization, fall prevention, use of orthoses, and noninvasive surgical procedures is emerging as a promising approach. Summary Clinically, these findings should imply greater emphasis on high impact exercise during skeletal growth and on maintenance of weight bearing and balance training in the later years. Future research should examine the effect of these interventions on fracture prevention. C1 [Schwab, Pascale] Oregon Hlth & Sci Univ, Div Arthritis & Rheumat Dis, Portland, OR 97239 USA. [Schwab, Pascale; Klein, Robert F.] Portland VA Med Ctr, Portland, OR USA. [Klein, Robert F.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR USA. RP Schwab, P (reprint author), Oregon Hlth & Sci Univ, Div Arthritis & Rheumat Dis, 3181 SW Sam Jackson Pk Rd,OP09, Portland, OR 97239 USA. EM schwabp@ohsu.edu FU NIAMS NIH HHS [R01 AR044659-08, R01 AR044659] NR 46 TC 19 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2008 VL 20 IS 2 BP 213 EP 217 PG 5 WC Rheumatology SC Rheumatology GA 266YW UT WOS:000253475200016 PM 18349754 ER PT J AU Keskin, DB Stern, JNH Fridkis-Hareli, M Ahmed, AR AF Keskin, Derin B. Stern, Joel N. H. Fridkis-Hareli, Masha Ahmed, A. Razzaclue TI Cytokine profiles in pemphigus vulgaris patients treated with intravenous immunoglobulins as compared to conventional immuno suppressive therapy SO CYTOKINE LA English DT Article DE pemphigus vulgaris; cytokine and chemokine profiles; conventional immunosuppressive therapy; intravenous immunoglobulin; clinical course ID NECROSIS-FACTOR-ALPHA; TERM FOLLOW-UP; BLISTERING DISEASES; ADJUVANT THERAPY; DENDRITIC CELLS; PULSE THERAPY; ANTIBODIES; AUTOIMMUNE; CYCLOPHOSPHAMIDE; AUTOANTIBODIES AB Pemphigus vulgaris (PV) is a potentially fatal blistering disease of the skin and mucous membranes, characterized by the presence of autoantibodies against adhesion molecules (desmoglein, Dsg3) present on the surface of keratinocytes, which lead to the loss of cellular adhesion or acantholysis. The mainstay of treatment is conventional immunosuppressive therapy (CIST), i.e. high dose, long-term systemic corticosteroids with or without immunosuppressive drugs. Intravenous immunoglobulin (IVIg) has been used in patients refractory to CIST, and its use has resulted in long-term clinical remission. Since cytokines play an important role in the immunopathogenesis of PV, it would be useful to compare how both IVIg and CIST therapies affect cytokine levels in the serum of PV patients. Thus, the goal of this study was to conduct a comparative analysis of levels of various cytokines, during an 18 month consecutive period, after the initiation of CIST or IVIg treatment in PV patients, with similar extent and severity of disease in the two study groups, with I I patients in each group. The cytokines measured were IL-1 beta, IL-6, IL-8, IFN-gamma, IL-4 and IL-10. The levels of most of these cytokines were higher in the sera of untreated patients in both groups, compared to normal controls. The cumulative data collected over an 18 month period of treatment demonstrates that there is a gradual reduction in the levels of these cytokines, until they are at levels observed in normal individuals. The conclusions from this limited number of patients, prospectively studied, would suggest that both CIST and IVIg therapies are similar in their ability to influence a panel of cytokines in patients with pemphigus vulgaris. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Ahmed, A. Razzaclue] New England Bapist Hosp, Dept Med, Ctr Blistering Dis, Boston, MA 02120 USA. [Keskin, Derin B.; Stern, Joel N. H.; Fridkis-Hareli, Masha] Dana Faber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. [Keskin, Derin B.; Stern, Joel N. H.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), New England Bapist Hosp, Dept Med, Ctr Blistering Dis, 70 Parker Hill Ave,Suite 208, Boston, MA 02120 USA. EM arahmedmd@msn.com OI Stern, Joel N.H./0000-0002-1259-2256 NR 71 TC 23 Z9 25 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR PY 2008 VL 41 IS 3 BP 315 EP 321 DI 10.1016/j.cyto.2007.12.007 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 285PI UT WOS:000254788300018 PM 18289869 ER PT J AU Williams, BR Woodby, LL Bailey, FA Burgio, KL AF Williams, Beverly R. Woodby, Lesa L. Bailey, F. Amos Burgio, Kathryn L. TI Identifying and responding to ethical and methodological issues in after-death interviews with next-of-kin SO DEATH STUDIES LA English DT Review ID BEREAVED FAMILY-MEMBERS; INFORMAL CAREGIVERS SATISFACTION; RANDOMIZED CONTROLLED-TRIAL; DYING CANCER-PATIENTS; PALLIATIVE CARE; LIFE CARE; QUALITATIVE RESEARCH; PATIENTS PAIN; ILL PATIENTS; EVENT SCALE AB After-death research with next-of-kin can enhance our understanding of end-of-life care and translate into better services for dying persons and their survivors. This article describes ethical and methodological issues that emerged in a pilot of a face-to-face interview guide designed to elicit next-of-kin's perceptions of end-of-life care. The pilot study was part of a larger Veterans Affairs (VA) Health Services Research protocol to improve end-of-life care in VA Medical Centers. By deconstructing the research process from an ethical perspective and engaging in critical self-assessment, the authors aim to inform other researchers of potential problems involved in after-death research with next-of-kin. C1 [Williams, Beverly R.; Woodby, Lesa L.; Bailey, F. Amos; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ Clin Ctr GREC, Dept Vet Affairs Med Ctr, Birmingham, AL USA. [Williams, Beverly R.; Woodby, Lesa L.; Bailey, F. Amos; Burgio, Kathryn L.] Univ Alabama, Dept Med, Div Gerontol Geriat & Palliat Care, Birmingham, AL USA. RP Williams, BR (reprint author), Birmingham VA Med Ctr, Dept Vet Affairs, 700 S 19th St,11-G, Birmingham, AL 35233 USA. EM beverly.williams3@va.gov NR 117 TC 18 Z9 18 U1 0 U2 4 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PD MAR PY 2008 VL 32 IS 3 BP 197 EP 236 DI 10.1080/07481180701881297 PG 40 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 285BG UT WOS:000254751700001 PM 18705168 ER PT J AU Schalock, PC Zug, KA Carter, JC Dhar, D MacKenzie, T AF Schalock, Peter C. Zug, Kathryn A. Carter, Joi C. Dhar, Damien MacKenzie, Todd TI Efficacy and patient perception of grenz ray therapy in the treatment of dermatoses refractory to other medical therapy SO DERMATITIS LA English DT Article ID DERMATOLOGICAL TRAINING CENTERS; BLIND BILATERAL TRIAL; IONIZING-RADIATION AB Background: Grenz ray therapy (GRT) has been used to treat dermatoses refractory to other therapy. Patient's assessments to GRT alone have not been previously reported. Objective (1) To report the patterns of use of GRT at our center over a 10-year period and evaluate the efficacy of GRT in treating recalcitrant skin conditions, (2) to evaluate patient perceptions about GRT, and (3) to evaluate whether patients felt this form of treatment was worthwhile. Method. Cross-sectional survey by mailed questionnaire to patients treated with GRT from 1990 to 2001. Results: Of 351 patients treated with GRT from 1990 to 2001, 98 (28%) returned the questionnaire; 64% reported decreased severity or clearing of disease (p = .003), and 63% reported decreased or no discomfort (p = .006) 3 months following treatment. Overall, 54% said GRT was worthwhile, and 53% would choose it again; 40% reported mild side effects. Number of treatments (p = .2) or total dose (p = .25) were not significantly different among responders to GRT and nonresponders to GRT. In a subgroup of treated patients with a diagnosis of contact dermatitis (94% with hand dermatitis), 64% felt GRT was worthwhile and 77% indicated that they would choose this therapy again if needed. Conclusions: Many patients treated with GRT for recalcitrant dermatitis reported that this treatment was an effective therapy in decreasing the discomfort and severity of their skin condition. Overall, just more than half of treated patients believed GRT was a worthwhile therapy that they would use again. C1 [Schalock, Peter C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med Dermatol, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med & Internal Med, Lebanon, NH 03766 USA. RP Schalock, PC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1710-3568 J9 DERMATITIS JI Dermatitis PD MAR-APR PY 2008 VL 19 IS 2 BP 90 EP 94 DI 10.2310/6620.2007.06057 PG 5 WC Dermatology SC Dermatology GA 305MH UT WOS:000256182000005 PM 18413110 ER PT J AU Holzmann, RD Guldbakke, KK Schanbacher, CF AF Holzmann, Ruth Dorothee Guldbakke, Kjetil Kris Schanbacher, Carl Frank TI Bilateral advancement flaps with helical rim Z-plasty modification for management of ear defects SO DERMATOLOGIC SURGERY LA English DT Article ID RETROAURICULAR SKIN; RECONSTRUCTION; SURGERY; REPAIR C1 [Holzmann, Ruth Dorothee; Guldbakke, Kjetil Kris; Schanbacher, Carl Frank] Dana Farber Canc Inst, Boston, MA 02115 USA. [Holzmann, Ruth Dorothee; Guldbakke, Kjetil Kris; Schanbacher, Carl Frank] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA USA. [Holzmann, Ruth Dorothee] Charite Univ Med Berlin, Dept Dermatol, D-13353 Berlin, Germany. [Guldbakke, Kjetil Kris] Univ Trondheim Hosp, St Olavs Hosp, Trondheim, Norway. RP Holzmann, RD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rdholzmann@mac.com NR 23 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2008 VL 34 IS 3 BP 374 EP 377 DI 10.1111/j.1524-4725.2007.34072.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 268WC UT WOS:000253609700013 PM 18190549 ER PT J AU Holzmann, RD Astner, S Forschner, T Sterry, G AF Holzmann, Ruth D. Astner, Susanne Forschner, Tobias Sterry, Gerda TI Scar sarcoidosis in a child: Case report of successful treatment with the pulsed dye laser SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID CUTANEOUS SARCOIDOSIS C1 [Holzmann, Ruth D.; Astner, Susanne; Forschner, Tobias; Sterry, Gerda] Charite Univ Med Berlin, Dept Dermatol, D-10117 Berlin, Germany. [Holzmann, Ruth D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Dermatol, Boston, MA 02115 USA. RP Holzmann, RD (reprint author), Charite Univ Med Berlin, Dept Dermatol, Charite Pl 1, D-10117 Berlin, Germany. EM ruth.holzmann@charite.de NR 14 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2008 VL 34 IS 3 BP 393 EP 396 DI 10.1111/j.1524-4725.2007.34077.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 268WC UT WOS:000253609700018 PM 18190544 ER PT J AU Guldbakke, KK Brodsky, J Liang, M Schanbacher, CF AF Guldbakke, Kjetil K. Brodsky, Joshua Liang, Michelle Schanbacher, Carl F. TI Human papillomavirus type 73 in primary and recurrent periungual squamous cell carcinoma SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MUCOSAL HUMAN-PAPILLOMAVIRUS; NAIL BED; CERVICAL-CANCER; BOWENS-DISEASE; HPV TYPES; LONGITUDINAL MELANONYCHIA; TRANSPLANT RECIPIENTS; MICROGRAPHIC SURGERY; VERRUCOUS CARCINOMA C1 [Guldbakke, Kjetil K.; Schanbacher, Carl F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Dermatol, Boston, MA 02115 USA. [Guldbakke, Kjetil K.] Univ Trondheim Hosp, Dept Dermatol, St Olavs Hosp, Trondheim, Norway. [Brodsky, Joshua] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Liang, Michelle] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. RP Schanbacher, CF (reprint author), 321 Columbus Ave, Boston, MA 02115 USA. EM cschanbacher@gmail.com NR 68 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2008 VL 34 IS 3 BP 407 EP 413 DI 10.1111/j.1524-4725.2007.34081.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 268WC UT WOS:000253609700022 PM 18248476 ER PT J AU Macdonald, HZ Beeghly, M Grant-Knight, W Augustyn, M Woods, RW Cabral, H Rose-Jacobs, R Saxe, GN Frank, DA AF Macdonald, Helen Z. Beeghly, Marjorie Grant-Knight, Wanda Augustyn, Marilyn Woods, Ryan W. Cabral, Howard Rose-Jacobs, Ruth Saxe, Glenn N. Frank, Deborah A. TI Longitudinal association between infant disorganized attachment and childhood posttraumatic stress symptoms SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID PRENATAL COCAINE EXPOSURE; DEVELOPMENTAL PSYCHOPATHOLOGY; BEHAVIOR PROBLEMS; EXTERNALIZING PROBLEMS; MATERNAL-BEHAVIOR; OLDER ADOLESCENTS; DISORDER; CHILDREN; MALTREATMENT; PATTERNS AB The purpose of this study was to evaluate whether children with a history of disorganized attachment in infancy were more likely than children without a history of disorganized attachment to exhibit symptoms of posttraumatic stress disorder (PTSD) at school age following trauma exposure. The sample consisted of 78 8.5-year-old children from a larger, ongoing prospective study evaluating the effects of intrauterine cocaine exposure (IUCE) on children's growth and development from birth to adolescence. At the 12-month visit, children's attachment status was scored from videotapes of infant-caregiver dyads in Ainsworth's strange situation. At the 8.5-year visit, children were administered the Violence Exposure Scale-Revised, a child-report trauma exposure inventory, and the Diagnostic Interview for Children and Adolescents by an experienced clinical psychologist masked to children's attachment status and IUCE status. Sixteen of the 78 children (21%) were classified as insecure-disorganized/insecure-other at 12 months. Poisson regressions covarying IUCE, gender, and continuity of maternal care indicated that disorganized attachment status at 12 months, compared with nondisorganized attachment status, significantly predicted both higher avoidance cluster PTSD symptoms and higher reexperiencing cluster PTSD symptoms. These findings suggest that the quality of early dyadic relationships may be linked to differences in children's later development of posttraumatic stress symptoms following a traumatic event. C1 [Macdonald, Helen Z.] VA Boston Healthcare Syst, Nat Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Macdonald, Helen Z.; Augustyn, Marilyn; Cabral, Howard; Rose-Jacobs, Ruth; Frank, Deborah A.] Boston Univ, Boston, MA 02215 USA. [Beeghly, Marjorie] Wayne State Univ, Detroit, MI 48202 USA. [Saxe, Glenn N.] Childrens Hosp Boston, Boston, MA USA. [Beeghly, Marjorie; Saxe, Glenn N.] Harvard Univ, Cambridge, MA 02138 USA. [Grant-Knight, Wanda] Rehabil Inst Chicago, Chicago, IL USA. [Woods, Ryan W.] Univ Wisconsin, Madison, WI 53706 USA. RP Macdonald, HZ (reprint author), VA Boston Healthcare Syst, Nat Ctr PTSD, Behav Sci Div, 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. OI Rose-Jacobs, Ruth/0000-0003-4498-9570; Cabral, Howard/0000-0002-1185-8331; Frank, Deborah/0000-0002-2178-0865; Saxe, Glenn/0000-0002-4756-1169 FU NCRR NIH HHS [M01 RR000533-340216, M01 RR000533, M01 RR000533-330216, M01 RR000533-350216, M01 RR000533-360216, M01RR00533]; NIDA NIH HHS [R01 DA006532, R01DA6532] NR 62 TC 31 Z9 32 U1 8 U2 24 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 2008 VL 20 IS 2 BP 493 EP 508 DI 10.1017/S0954579408000242 PG 16 WC Psychology, Developmental SC Psychology GA 293HX UT WOS:000255327500006 PM 18423091 ER PT J AU Shapiro, A Matheny, M Zhang, Y Tumer, N Cheng, KY Rogrigues, E Zolotukhin, S Scarpace, PJ AF Shapiro, Alexandra Matheny, Michael Zhang, Yi Tumer, Nihal Cheng, Kit-Yan Rogrigues, Enda Zolotukhin, Sergei Scarpace, Philip J. TI Synergy between leptin therapy and a seemingly negligible amount of voluntary wheel running prevents progression of dietary obesity in leptin-resistant rats SO DIABETES LA English DT Article ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; SIGNAL-TRANSDUCTION; VISCERAL OBESITY; BODY-WEIGHT; MICE; RESPONSES; EXERCISE; PURIFICATION; INHIBITION; EXPRESSION AB OBJECTIVE-We examined whether chronic leptin treatment of diet-induced obese rats promotes or alleviates the susceptibility to continued high-fat feeding. Second, we examined if voluntary wheel running is beneficial in reducing the trajectory of weight gain in high-fat-raised leptin-resistant rats. RESEARCH DESIGN AND METHODS-Sprague-Dawley rats were fed a standard diet or a high-fat diet for 5 months, and then hypothalamic leptin overexpression was induced through central administration of adeno-associated virus-encoding leptin while continuing either the standard or high-fat diet. Two weeks later, half of the rats in each group were provided access to running wheels for 38 days while being maintained on either a standard or high-fat diet. RESULTS-In standard diet-raised rats, either wheel running or leptin reduced the trajectory of weight gain, and the combined effect of both treatments was additive. In high-fat-raised leptin-resistant rats, leptin overexpression first transiently reduced weight gain but then accelerated the weight gain twofold over controls. Wheel running in high-fat-raised rats was sixfold less than in standard diet-raised rats and did not affect weight gain. Surprisingly, wheel running plus leptin completely prevented weight gain. This synergy was associated with enhanced hypothalamic signal transducer and activator of transcription (STAT) 3 phosphorylation and suppressor of cytokine signaling 3 expression in wheel running plus leptin compared with leptin-treated sedentary high-fat counterparts. This enhanced STAT3 signaling associated with the combination treatment occurred only in high-fat-raised, leptin-resistant rats and not in standard diet-raised, leptin-responsive rats. CONCLUSIONS-Chronic leptin treatment in diet-induced obese rats accelerates dietary obesity. However, leptin combined with wheel running prevents further dietary weight gain. Thus, this combination therapy may be a viable antiobesity treatment. C1 [Shapiro, Alexandra; Matheny, Michael; Zhang, Yi; Tumer, Nihal; Cheng, Kit-Yan; Rogrigues, Enda; Scarpace, Philip J.] Univ Florida, Dept Pharm & Therapeut, Gainesville, FL 32610 USA. [Zhang, Yi; Tumer, Nihal] US Dept Vet Affairs, Med Ctr, Gainesville, FL USA. [Tumer, Nihal; Scarpace, Philip J.] Univ Florida, Coll Med, Dept Aging & Geriatr, Gainesville, FL USA. [Zolotukhin, Sergei] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. RP Scarpace, PJ (reprint author), Univ Florida, Dept Pharm & Therapeut, Box 100267, Gainesville, FL 32610 USA. EM scarpace@ufi.edu FU NIA NIH HHS [P30 AG028740, AG-26159]; NIDDK NIH HHS [R01 DK62302] NR 35 TC 23 Z9 23 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2008 VL 57 IS 3 BP 614 EP 622 DI 10.2337/db07-0863 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PJ UT WOS:000253800900015 PM 18086903 ER PT J AU Pani, LN Nathan, DN Grant, RW AF Pani, Lydie Nkwimi Nathan, David Niatthew Grant, Richard William TI Clinical predictors of disease progression and medication initiation in untreated patients with type 2 diabetes and A1C less than 7% SO DIABETES CARE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2007 CL Chicago, IL SP Amer Diabet Assoc ID POOR GLYCEMIC CONTROL; PRIMARY-CARE; ETHNIC-DIFFERENCES; RISK-FACTORS; MELLITUS; INSULIN; ADULTS; MANAGEMENT; THERAPY; COMPLICATIONS AB OBJECTIVE - Many patients with early diabetes remain untreated. Our objectives were to identify clinical predictors of 1) worsening glycemic control and 2) medical treatment initiation in response to worsening glycemic control among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - We identified 5,804 type 2 diabetic patients seen at least twice between June 2005 and June 2006 within our 12-clinic primary care network. We examined predictors of diabetes progression (A1C >= 7% or initiation of hypoglycemic agent) over a 1-year follow-up period in 705 patients who had A1C <7% and were not on glucose-lowering medications at baseline. In the 200 patients in this group who progressed, we examined predictors of medical therapy initiation. RESULTS - In multivariate analyses, baseline A1C (P < 0.0001), younger age (P = 0.04), and weight gain (P = 0.03) were independent predictors of progression after adjusting for race, sex, and baseline HDL levels. Each decade of increasing age reduced the risk of progression by 15%. Each 1-lb increase in weight was associated with a 2% increased odds of progression. Likelihood of medication initiation among progressors decreased by 40% (P = 0.02) with every decade of age and decreased by 2.3% (P = 0.02) with each 1-mg/dl decrease in LDL level from baseline after adjusting for race, sex, and weight change. CONCLUSIONS - Among untreated primary care patients with type 2 diabetes and A1C <7%, younger patients and those with weight gain were more likely to have diabetes progression and should be the focus of aggressive diabetes management. C1 Massachusetts Gen Hosp, Dept Med, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pani, LN (reprint author), Massachusetts Gen Hosp, Diabet Unit, Diabetes Off, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. EM lpani@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452, K23 DK067452-04] NR 26 TC 29 Z9 29 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 MAR PY 2008 VL 31 IS 3 BP 386 EP 390 DI 10.2337/dc07-1934 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100002 PM 18083790 ER PT J AU Schwartz, AV Vittinghoff, E Sellmeyer, DE Feingold, KR de Rekeneire, N Strotmeyer, ES Shorr, RI Vinik, AI Odden, MC Park, SW Faulkner, KA Harris, TB AF Schwartz, Ann V. Vittinghoff, Eric Sellmeyer, Deborah E. Feingold, Kenneth R. de Rekeneire, Nathalie Strotmeyer, Elsa S. Shorr, Ronald I. Vinik, Aaron I. Odden, Michelle C. Park, Seok Won Faulkner, Kimberly A. Harris, Tamara B. CA Hlth Aging Body Composition Study TI Diabetes-related complications, glycemic control, and falls in older adults SO DIABETES CARE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res ID CREATININE CLEARANCE; ELDERLY RESIDENTS; WOMENS HEALTH; RISK-FACTORS; CYSTATIN-C; NEUROPATHY; MEN; AGE AB OBJECTIVE - Older adults with type 2 diabetes are more likely to fall, but little is known about risk factors for falls in this population. We determined whether diabetes-related complications or treatments are associated with risk of falls in older diabetic adults. RESEARCH DESIGN AND METHODS -In the Health, Aging, and Body Composition cohort of well-functioning older adults participants reported falls in the previous year at annual visits. Odds ratios (ORs) for more frequent falls among 446 diabetic participants whose mean age was 73.6 years, with an average follow-up of 4.9 years, were estimated with continuation ratio models. RESULTS - in the first year, 24% reported falling; 22, 26, 3 1, and 30% fell in subsequent years. In adjusted models, reduced peroneal nerve response amplitude (OR 1.50 -95% CI 1.07-2.12], worst quartile versus others); higher cystatin-C, a marker of reduced renal function (1.38 [1.11-1.71], for 1 SD increase); poorer contrast sensitivity (1.41 [0.97-2.04], worst quartile versus others); and low A1C in insulin users (4.36 [1.32-14.461, A1C <= 6 vs. >8%) were associated with risk of falls. In those using oral hypoglycemic medications but not insulin, low A1C was not associated With risk of falls (1.29 [0.65-2.54], A1C <= 6 vs. >8%). Adjustment for physical performance explained some, but not all, of these associations. CONCLUSIONS - in older diabetic adults, reducing diabetes-related complications may prevent falls. Achieving lower A1C levels with oral hypoglycemic medications was not associated with more frequent falls, but, among those using insulin, A1C <= 6% increased risk of falls. C1 [Schwartz, Ann V.; Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Sellmeyer, Deborah E.; Feingold, Kenneth R.] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94107 USA. [de Rekeneire, Nathalie; Harris, Tamara B.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Strotmeyer, Elsa S.; Park, Seok Won; Faulkner, Kimberly A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Shorr, Ronald I.] Univ Florida, Div Geriatr, Dept Aging & Geriatr Res, Gainesville, FL USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Strelitz Diabet Inst, Dept Internal Med, Norfolk, VA 23501 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Anat & Pathol, Norfolk, VA 23501 USA. [Odden, Michelle C.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Park, Seok Won] Pochon CHA Univ, Dept Internal Med, Gyeonggi Do, South Korea. RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St, San Francisco, CA 94107 USA. EM aschwartz@psg.ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, N01-AG-6-2101]; NIDDK NIH HHS [R21 DK064597, R21 DK064597-02] NR 31 TC 138 Z9 140 U1 1 U2 5 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 MAR PY 2008 VL 31 IS 3 BP 391 EP 396 DI 10.2337/dc07-1152 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100003 PM 18056893 ER PT J AU Goebel-Fabbri, AE Fikkan, J Franko, DL Pearson, K Anderson, BJ Weinger, K AF Goebel-Fabbri, Ann E. Fikkan, Janna Franko, Debra L. Pearson, Kimberly Anderson, Barbara J. Weinger, Katie TI Insulin restriction and associated morbidity and mortality in women with type 1 diabetes SO DIABETES CARE LA English DT Article ID EATING-DISORDERS; ANOREXIA-NERVOSA; COMPLICATIONS; VALIDATION; INVENTORY; ATTITUDES; MELLITUS; OUTCOMES; FEMALES; IDDM AB OBJECTIVE - To determine whether insulin restriction increases morbidity and mortality in women with type 1 diabetes. RESEARCH DESIGN AND METHODS - This is an 11-year follow-up study of women with type 1 diabetes. A total of 234 women (60% of the original cohort) participated in the follow-up. Mean age was 45 years and mean diabetes duration was 28 years at follow-up. Mean BMI was 25 kg/m(2) and mean A1C was 7.9%. Measures of diabetes self-care behaviors, diabetes-specific distress, fear of hypoglycemia, psychological distress, and eating disorder symptoms were administered at baseline. At follow-up, mortality data were collected through state and national databases. Follow-up data regarding diabetes complications were gathered by self-report. RESULTS - Seventy-one women (30%) reported insulin restriction at baseline. Twenty-six women died during follow-up. Based on multivariate Cox regression analysis, insulin restriction conveyed a threefold increased risk of mortality after controlling for baseline age, BMI, and A1C. Mean age of death was younger for insulin restrictors (45 vs. 58 years, P < 0.01). insulin restrictors reported higher rates of nephropathy and foot problems at follow-up. Deceased women had reported more frequent insulin restriction (P < 0.05) and reported more eating disorder symptoms (P < 0.05) at baseline than their living counterparts. CONCLUSIONS - Our data demonstrate that insulin restriction is associated with increased rates of diabetes complications and increased mortality risk. Mortality associated with insulin restriction appeared to occur in the context of eating disorder symptoms, rather than other psychological distress. We propose a screening question appropriate for routine diabetes care to improve detection of this problem. C1 [Goebel-Fabbri, Ann E.; Fikkan, Janna; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Goebel-Fabbri, Ann E.; Pearson, Kimberly; Weinger, Katie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Pearson, Kimberly] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Anderson, Barbara J.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Suite 350,1 Joslin Pl, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [P30DK36836] NR 24 TC 76 Z9 77 U1 3 U2 7 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 MAR PY 2008 VL 31 IS 3 BP 415 EP 419 DI 10.2337/dc07-2026 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100007 PM 18070998 ER PT J AU Watson, AJ Bell, AG Kvedar, JC Grant, RW AF Watson, Alice J. Bell, Alastair G. Kvedar, Joseph C. Grant, Richard W. TI Reevaluating the digital divide: Current lack of internet use is not a barrier to adoption of novel health information technology SO DIABETES CARE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2007 CL Chicago, IL SP Amer Diabet Assoc ID PRIMARY-CARE; MANAGEMENT; VALIDITY C1 [Watson, Alice J.; Bell, Alastair G.; Kvedar, Joseph C.] Ctr Connected Hlth, Boston, MA USA. [Watson, Alice J.; Kvedar, Joseph C.; Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA. [Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Watson, AJ (reprint author), 25 New Chardon St,Suite 400D, Boston, MA 02114 USA. EM ajwatson@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452-03, K23 DK067452] NR 11 TC 12 Z9 12 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 MAR PY 2008 VL 31 IS 3 BP 433 EP 435 DI 10.2337/dc07-1667 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100011 PM 18056885 ER PT J AU Lopez, X Castells, M Ricker, A Velazquez, EF Mun, E Goldfine, AB AF Lopez, Ximena Castells, Mariana Ricker, Alyne Velazquez, Elsa F. Mun, Edward Goldfine, Allison B. TI Human insulin analog-induced lipoatrophy SO DIABETES CARE LA English DT Article ID ATOPIC-DERMATITIS; DISODIUM-CROMOGLYCATE; SODIUM CROMOGLYCATE; MAST-CELLS; CHILDREN; RAT AB OBJECTIVE - To characterize the pathophysiology of recombinant human insulin-induced lipoatrophy. RESEARCH DESIGN AND METHODS - We performed immunologic laboratory evaluation and skin testing for different insulin analogs and diluents in patients with type I diabetes and severe insulin-induced local lipoatrophy. Subcutaneous adipose tissue biopsies of areas of acute (7 days) and chronic insulin administration were examined. Topical sodium cromolyn was applied twice a day to atrophic areas and prophylactically to new sites of insulin administration. RESULTS - Subcutaneous adipose biopsies showed an elevated population of tryptase-positive, chymase-positive degranulated mast cells. Of five patients treated with topical sodium cromolyn., none had new lipoatrophic sites and four showed improvements in old lesions. CONCLUSIONS - Tryptase-positive/chymase-postitive mast cells, known to be sensitive to sodium cromolyn, may contribute to the destructive immune process mediated in response to exogenous insulin. Mast cell stabilizing therapy with topical cromolyn may reverse early and prevent new lipoatrophic lesions. C1 [Lopez, Ximena; Ricker, Alyne; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Castells, Mariana; Velazquez, Elsa F.; Mun, Edward; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lopez, Ximena; Castells, Mariana; Ricker, Alyne; Velazquez, Elsa F.; Mun, Edward; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [DK 36836, R01DK070648] NR 6 TC 17 Z9 17 U1 0 U2 0 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 MAR PY 2008 VL 31 IS 3 BP 442 EP 444 DI 10.2337/dc07-1739 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100014 PM 18162498 ER PT J AU Ginde, AA Espinola, JA Camargo, CA AF Ginde, Adit A. Espinola, Janice A. Camargo, Carlos A., Jr. TI Trends and disparities in US emergency department visits for hypoglycemia, 1993-2005 SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; DIABETES-MELLITUS; INSULIN; COMPLICATIONS; FREQUENCY; TYPE-1; COHORT AB OBJECTIVE - To characterize the epidemiology of hypoglycemia in U.S. emergency departments. RESEARCH DESIGN AND METHODS - We analyzed data from the 1993-2005 National Hospital Ambulatory Medical Care Survey and evaluated trends and disparities over time. RESULTS - There were similar to 5 million emergency department visits for hypoglycemia from 1993-2005, and 25% resulted in hospital admission. The visit rate per 1,000 of the diabetic population was 34 (95% CI 30-37) and did not change significantly during the study period (P = 0.70 for trend). These visit rates were higher in patients aged < 45 years (n = 62) and >= 75 years (n = 54) versus those aged 45-74 years (n = 21), in female (n = 37) versus male (n = 30) patients, in black (n = 40) vs. white (n = 25) patients, and in Hispanic (n = 21) versus non-Hispanic (n = 12) patients (all P < 0.001). CONCLUSIONS - Greater emphasis on intensive glycemic control has not resulted in increased emergency department visit rates for hypoglycemia. We identified demographic disparities, however, that merit further evaluation. The emergency department provides an important opportunity for epidemiologic study and intervention for severe hypoglycemia. C1 Univ Colorado, Hlth Sci Ctr, Dept Emergency Med, Aurora, CO 80045 USA. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Ginde, AA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@uchsc.edu RI Siry, Bonnie/D-7189-2017 NR 19 TC 45 Z9 45 U1 0 U2 0 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 MAR PY 2008 VL 31 IS 3 BP 511 EP 513 DI 10.2337/dc07-1790 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100029 PM 18025407 ER PT J AU Caballero, AE Bousquet-Santos, K Robles-Osorio, L Montagnani, V Soodini, G Porramatikul, S Hamdy, O Nobrega, ACL Horton, ES AF Caballero, A. Enrique Bousquet-Santos, Kelb Robles-Osorio, Ludivina Montagnani, Valeria Soodini, Geetha Porramatikul, Sriurai Hamdy, Osama Nobrega, Antonio C. L. Horton, Edward S. TI Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; BETA-CELL FUNCTION; OBESE CHILDREN; METABOLIC SYNDROME; ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; MASS INDEX AB OBJECTIVE - We measured plasma markers of endothelial dysfunction, vascular inflammation, and pro-coagulation in obese Hispanic/Latino children and adolescents with normal glucose tolerance and determined their relationship to body composition and indexes of glucose and lipid metabolism. RESEARCH DESIGN AND METHODS - A total of 38 lean or obese Hispanic children and adolescents (10-18 years of age) were selected. The overweight group (n = 21) had a BMI > 85th percentile for their age and sex, and the lean group (n = 17) had a BMI between the 25th and 50th percentiles. Studies included an oral glucose tolerance test, measurements of plasma glucose and lipids, several markers of endothelial function and inflammation, and determination of body composition by dual X-ray absorptiometry. RESULTS - The obese group had higher systolic blood pressure and plasma triglycerides and was more insulin resistant than the lean group. The obese group also had higher plasma soluble intercellular adhesion molecule (259.5 +/- 60.0 vs. 223.2 +/- 47.5 ng/ml, P = 0.047), tumor necrosis factor-alpha (2.57 +/- 1.1 vs. 1.74 +/- 0.6 pg/ml, P = 0.008), high-sensitivity C-reactive protein (2.0 vs. 0.13 mg/l, P < 0.0001), plasminogen-activated inhibitor-1 (47.0 +/- 35.7 vs. 12.0 +/- 5.2 ng/ml, P < 0.0001), tissue plasminogen activator (6.1 +/- 1.9 vs. 4.1 +/- 0.8 ng/ml,P = 0.001), and white blood cell count (6.9 vs. 5.3 X 10(3), p = 0.031) and lower levels of adiponectin (8.7 +/- 3.3 vs. 12.6 +/- 5.2 mu g/ml, P = 0.022). No significant differences were observed for soluble vascular cell adhesion molecule or interleukin-6. CONCLUSIONS - Overweight Hispanic children and adolescents with norma glucose tolerance exhibit increased plasma markers of endothelial dysfunction and subclinical inflammation in association with obesity and insulin resistance. These abnormalities may predispose them to the development of type 2 diabetes and cardiovascular disease. C1 [Caballero, A. Enrique; Robles-Osorio, Ludivina; Montagnani, Valeria; Soodini, Geetha; Porramatikul, Sriurai; Hamdy, Osama; Horton, Edward S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Latino Diabet Initiat,Clin Res Ctr, Boston, MA 02215 USA. [Bousquet-Santos, Kelb; Nobrega, Antonio C. L.] Univ Fed Fluminense, Inst Biomed, Dept Physiol & Pharmacol, Rio De Janeiro, Brazil. RP Caballero, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Latino Diabet Initiat,Clin Res Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM enrique.caballero@joslin.harvard.edu RI Nobrega, Antonio Claudio/F-4825-2012 OI Nobrega, Antonio Claudio/0000-0002-3830-2886 FU NCRR NIH HHS [RR01032] NR 42 TC 66 Z9 78 U1 1 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 MAR PY 2008 VL 31 IS 3 BP 576 EP 582 DI 10.2337/dc07-1540 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100042 PM 18083792 ER PT J AU Haas, LB AF Haas, Linda B. TI The role of the diabetes educator - Patient case scenarios SO DIABETES EDUCATOR LA English DT Article ID PREVENTING CARDIOVASCULAR-DISEASE; AMERICAN-HEART-ASSOCIATION; METABOLIC SYNDROME; RISK-FACTORS; INFLAMMATION; OBESITY; CALL AB Therapeutic lifestyle intervention, with a focus on weight loss, is the cornerstone of cardiometabolic risk factor reduction, but many patients find it difficult to make the changes that are needed to achieve meaningful improvements in risk markers. There are a variety of pharmacologic options for the management of individual risk factors, such as hypertension, dyslipidemia, and insulin resistance. However, agents that are currently available to assist patients in their weight loss efforts are limited by their potential for adverse effects. The American Association of Diabetes Educators ( AADE) has identified 7 behavioral targets of self- management, the AADE7 (TM) Self-Care Behaviors, which include healthy eating, being active, monitoring, taking medications, problem solving, healthy coping, and reducing risk factors. The case scenarios in the article illustrate some of the challenges clinicians face in managing cardiometabolic risk factor reduction in the context of these recommended behaviors. A common theme among these cases is the importance of assessing patients' understanding, beliefs, and readiness to change their behaviors. C1 Seattle Div, VA Puget Sound HCS, Seattle, WA 98108 USA. RP Haas, LB (reprint author), Seattle Div, VA Puget Sound HCS, S-118,1660 S Columbian Way, Seattle, WA 98108 USA. EM Linda.haas@va.gov NR 19 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2008 VL 34 SU 2 BP 32S EP 36S DI 10.1177/0145721708316769 PG 5 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 288PS UT WOS:000254998900002 ER PT J AU Alm, M Soroudi, N Wylie-Rosett, J Isasi, CR Suchday, S Rieder, J Khan, U AF Alm, Mary Soroudi, Nafisseh Wylie-Rosett, Judith Isasi, Carmen R. Suchday, Sonia Rieder, Jessica Khan, Unab TI A qualitative assessment of barriers and facilitators to achieving behavior goals among obese inner-city adolescents in a weight management program SO DIABETES EDUCATOR LA English DT Article ID DISEASE RISK; BODY-IMAGE AB Purpose The purpose of this study was (1) to examine the reasons for managing weight, (2) to investigate the barriers and facilitators to achieving behavior goals, and (3) to assess how a behavior coach affects the goal-setting process of obese inner-city adolescents in a weight management program. Methods Obese adolescents participating in a pilot study assessing the role of a behavior coach on successful weight management (n = 18) were interviewed to identify barriers and facilitators to reaching behavior goals. Data were analyzed using descriptive statistics and the constant comparative method of qualitative analysis. Results In the rationale for weight control, adolescent girls and boys reported a desire to improve physical appearance and physical conditioning, respectively. Barriers to reaching physical activity goals among girls included unsafe neighborhoods and a negative body image. Maintaining unrealistic behavior and weight goals hindered satisfaction with behavior change and weight loss (in both genders. Overall, coaching provided support that helped the obese teens feel more successful in the goal-setting process and address issues related to their disruptive environments. Conclusions Diabetes educators can include a behavior coach as part of a weight management program to help teens set behavior goals and overcome barriers to reaching behavior goals. C1 [Alm, Mary] Univ Minnesota, Dept Pediat & Adolescent Hlth, Minneapolis, MN 55455 USA. [Wylie-Rosett, Judith; Isasi, Carmen R.; Suchday, Sonia] Yeshiva Univ, Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Soroudi, Nafisseh] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rieder, Jessica; Khan, Unab] Montefiore Med Ctr, Div Adolescent Med, Dept Pediat, Bronx, NY 10467 USA. RP Alm, M (reprint author), Univ Minnesota, Dept Pediat & Adolescent Hlth, 200 Oak St SE,Suite 160, Minneapolis, MN 55455 USA. EM almx0002@umn.edu NR 24 TC 22 Z9 22 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2008 VL 34 IS 2 BP 277 EP 284 DI 10.1177/0145721708314182 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 288PQ UT WOS:000254998700007 PM 18375777 ER PT J AU Szadkowska, A Pietrzak, I Mianowska, B Bodalska-Lipinska, J Keenan, HA Toporowska-Kowalska, E Mlynarski, W Bodalski, J AF Szadkowska, A. Pietrzak, I. Mianowska, B. Bodalska-Lipinska, J. Keenan, H. A. Toporowska-Kowalska, E. Mlynarski, W. Bodalski, J. TI Insulin sensitivity in Type 1 diabetic children and adolescents SO DIABETIC MEDICINE LA English DT Article DE adolescents; children; diabetes; insulin sensitivity; obesity ID CARDIOVASCULAR RISK; METABOLIC SYNDROME; RESISTANCE; MELLITUS; OBESITY; PUBERTY; ATHEROSCLEROSIS; PREVALENCE; OVERWEIGHT; REMISSION AB Aim To estimate insulin sensitivity in Type 1 diabetic children and adolescents, and assess the relationship between insulin sensitivity and clinical markers of adiposity and parameters of the metabolic syndrome. Methods A total of 202 patients aged 8-18 years with Type 1 diabetes and disease duration 1.5-15 years participated. Insulin sensitivity was estimated by glucose uptake during an euglycaemic-hyperinsulinaemic clamp and was calculated as the average amount of glucose (M-lbm = mg/kg(lbm)/min) required to maintain euglycaemia. Blood pressure, glycated haemoglobin (HbA(1c)) and lipid concentrations were measured. Results The M-lbm value ranged from 4.14 to 25.25 mg/kg(lbm)/min (mean 9.81 +/- 3.34 mg/kg(lbm)/min). There was a significant relationship between M value and patients' age (r = -0.38, P < 0.0001). Insulin sensitivity decreased significantly with the onset of puberty; hence, it was significantly lower in pubertal and post-pubertal adolescents. Girls were significantly more insulin resistant than boys (9.01 +/- 0.32 vs. 10.43 +/- 0.29 mg/kg(lbm)/min, P = 0.005). Insulin sensitivity correlated with body mass index (r = -0.29, P < 0.001), waist circumference (r = -0.35, P < 0.001), triceps skin fold (r = -0.17, P = 0.018), subscapular skin fold (r = -0.23, P = 0.001) and body fat (r = -0.19, P = 0.006). There was a relationship between M-lbm value, cholesterol (r = -0.18, P = 0.012), high-density lipoprotein cholesterol (r = 0.15, P = 0.035), low-density lipoprotein cholesterol (r = -0.22, P = 0.002), triglycerides (r = -0.32, P < 0.001) and systolic blood pressure (r = -0.15, P = 0.029). Insulin resistance was related to HbA(1c) (r = -0.18, P = 0.012). Additionally, there was a correlation between M-lbm value and insulin dose. Conclusions Children and adolescents with Type 1 diabetes mellitus have a very wide range of insulin sensitivity, which is determined by sex, age, amount of adipose tissue and glycaemic control. C1 [Keenan, H. A.] Med Univ Lodz, Dept Childrens Dis, PL-91738 Lodz, Poland. [Keenan, H. A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Toporowska-Kowalska, E.] Med Univ Lodz, Dept Pediat Allergol Gastroenterol & Nutr, PL-91738 Lodz, Poland. RP Szadkowska, A (reprint author), Med Univ Lodz, Dept Childrens Dis, Sporna 36-50, PL-91738 Lodz, Poland. EM agnieszka.szadkowska@wp.pl RI Mianowska, Beata/S-9485-2016 NR 26 TC 28 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2008 VL 25 IS 3 BP 282 EP 288 DI 10.1111/j.1464-5491.2007.02357.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268VZ UT WOS:000253609300006 PM 18279410 ER PT J AU Weinger, K Jacobson, AM Musen, G Lyoo, IK Ryan, CM Jimerson, DC Renshaw, PF AF Weinger, K. Jacobson, A. M. Musen, G. Lyoo, I. K. Ryan, C. M. Jimerson, D. C. Renshaw, P. F. TI The effects of type 1 diabetes on cerebral white matter SO DIABETOLOGIA LA English DT Article DE brain structure; cognition; MRI; neuroimaging; type 1 diabetes; white matter hyperintensities ID STRUCTURED CLINICAL INTERVIEW; COGNITIVE PERFORMANCE; SIGNAL ABNORMALITIES; MACROVASCULAR COMPLICATIONS; SEVERE HYPOGLYCEMIA; RISK-FACTORS; HYPERINTENSITIES; INDIVIDUALS; LESIONS; VOLUNTEERS AB Aim/hypothesis Studies investigating the structure, neurophysiology and functional outcomes of white matter among type 1 diabetes patients have given conflicting results. Our aim was to investigate the relationship between type 1 diabetes and white matter hyperintensities. Method We assessed white matter integrity (using magnetic resonance imaging), depressive symptoms and neuropsychological function in 114 type 1 diabetes patients and 58 age-matched non-diabetic controls. Results Only Fazekas grade 1 and 2 white matter hyperintensities were found among 114 long-duration, relatively young diabetes patients; the severity of lesions did not differ substantially from 58 healthy controls. White matter hyperintensities were not associated with depressive history or with clinical characteristics of diabetes, including retinopathy, severe hypoglycaemia or glycaemia control. Conclusions/interpretation Our data do not support an association between diabetes characteristics and white matter hyperintensities among relatively young type 1 diabetes participants. C1 [Weinger, K.; Jacobson, A. M.; Musen, G.] Behav & Mental Hlth Res Joslin Diabet Ctr, Boston, MA 02459 USA. [Weinger, K.; Jacobson, A. M.; Musen, G.; Jimerson, D. C.; Renshaw, P. F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lyoo, I. K.; Renshaw, P. F.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Lyoo, I. K.] Seoul Natl Univ, Coll Med & Hosp, Seoul, South Korea. [Ryan, C. M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Jimerson, D. C.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. RP Weinger, K (reprint author), Behav & Mental Hlth Res Joslin Diabet Ctr, 1 Joslin Pl Suite 350, Boston, MA 02459 USA. EM katie.weinger@joslin.harvard.edu FU NCRR NIH HHS [RR 01032]; NIDDK NIH HHS [P30 DK36836]; PHS HHS [R01060754] NR 40 TC 36 Z9 40 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2008 VL 51 IS 3 BP 417 EP 425 DI 10.1007/s00125-007-0904-9 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 258RW UT WOS:000252888200007 PM 18157661 ER PT J AU Florez, JC Jablonski, KA McAteer, J Sandhu, MS Wareham, NJ Barroso, I Franks, PW Altshuler, D Knowler, WC AF Florez, J. C. Jablonski, K. A. McAteer, J. Sandhu, M. S. Wareham, N. J. Barroso, I. Franks, P. W. Altshuler, D. Knowler, W. C. CA Diabet Prevention Program Res Grp TI Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE beta cell function; diabetes prevention; genetic association study; single nucleotide polymorphism; type 2 diabetes; Wolfram syndrome ID GENOME-WIDE ASSOCIATION; TYPE-2; RISK AB Aims/hypothesis Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo. Methods We genotyped the WFS1 SNPs rs10010131, rs752854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year. Results Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r(2) = 0.88-1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75-0.97, p = 0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity. Conclusions/interpretation The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function. C1 [Florez, J. C.] George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. [Florez, J. C.; McAteer, J.; Altshuler, D.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.; Altshuler, D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Florez, J. C.; Altshuler, D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, J. C.; Altshuler, D.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Florez, J. C.; McAteer, J.; Altshuler, D.] MIT, Cambridge, MA 02139 USA. [Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Sandhu, M. S.; Wareham, N. J.] Strangeways Res Lab, MRC, Epidemiol Unit, Cambridge CB1 4RN, England. [Sandhu, M. S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England. [Barroso, I.] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, England. [Franks, P. W.] Umea Univ Hosp, Inst Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Altshuler, D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Knowler, W. C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Florez, JC (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Franks, Paul/0000-0002-0520-7604 FU Intramural NIH HHS; Medical Research Council [MC_U106179471]; NIDDK NIH HHS [K23 DK65978-04, U01 DK048489-06, K23 DK065978, R01 DK072041, R01 DK072041-02, U01 DK048489] NR 10 TC 40 Z9 43 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2008 VL 51 IS 3 BP 451 EP 457 DI 10.1007/s00125-007-0891-x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 258RW UT WOS:000252888200011 PM 18060660 ER PT J AU Kay, J AF Kay, Jonathan TI What causes nephrogenic systemic fibrosis? SO DIALYSIS & TRANSPLANTATION LA English DT Article ID RENAL-DIALYSIS PATIENTS; DERMOPATHY; INVOLVEMENT; GADOLINIUM C1 [Kay, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kay, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0090-2934 J9 DIALYSIS TRANSPLANT JI Dial. Transplant. PD MAR PY 2008 VL 37 IS 3 BP 95 EP 98 DI 10.1002/dat.20204 PG 4 WC Engineering, Biomedical; Transplantation; Urology & Nephrology SC Engineering; Transplantation; Urology & Nephrology GA 268YH UT WOS:000253615900003 ER PT J AU Tobi, M Kam, M Ullah, N Qureshi, K Yordanova, V Hatfield, J Fligiel, SEG Sochacki, P McGarrity, T Cole, C Lawson, M Jacoby, R AF Tobi, Martin Kam, Michael Ullah, Nadeem Qureshi, Kashif Yordanova, Violeta Hatfield, James Fligiel, Suzanne E. G. Sochacki, Paula McGarrity, Thomas Cole, Carolyn Lawson, Michael Jacoby, Russell TI An anti-adenoma antibody, adnab-9, may reflect the risk for neoplastic progression in familial hamartomatous polyposis syndromes SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Adnab-9; Peutz-Jeghers syndrome; familial juvenile polyposis; anti-alpha-defensin 5; Paneth-like cells ID PEUTZ-JEGHERS-SYNDROME; MONOCLONAL-ANTIBODY; JUVENILE POLYPOSIS; MARKER; GENE; CYCLOOXYGENASE-2; CANCER; CELLS AB Patients with the hamartomatous polyposis Peutz-Jeghers and familial juvenile polyposis syndromes are predisposed to colorectal cancer but lack early genetic alterations found in adenomatous premalignant lesions. We studied hamartomatous polyps for the expression of an early preneoplastic colorectal neoplasia risk marker also found in familial adenomatous polyposis patients. Retrospective, genetic, and hospital archival tissue immunohistochemistry using Adnab-9, a premalignant marker often found in Paneth-like cells (PCs), was performed on sections of polyps from eight patients with Peutz-Jeghers syndrome, eight patients with familial juvenile polyposis, and 36 hyperplastic polyp control sections. Anti-alpha-defensin 5 (AD5), a universal PC marker, was also used to label a subgroup of sections. Hamartomatous polyposis patients also underwent specific genetic analysis. Eighty-nine percent of Peutz-Jeghers syndrome polyps labeled with Adnab-9 compared with 63% for AD5; 88% of familial juvenile polyposis sections also labeled with Adnab-9. Of the 36 hyperplastic polyp sections, only four (11%) labeled with Adnab-9 and one (3%) with AD5. Adnab-9 labeling of PCs in the epithelial elements of hamartomatous colonic lesions of hereditary hamartomatous syndrome patients reflects the predisposition to colorectal cancer, further justifying early intervention strategies. C1 [Tobi, Martin] Philadelphia VAMC, Sect Gastroenterol MED 3GI, Philadelphia, PA 19104 USA. [Tobi, Martin; Kam, Michael; Ullah, Nadeem; Qureshi, Kashif; Yordanova, Violeta; Hatfield, James; Fligiel, Suzanne E. G.; Sochacki, Paula] Wayne State Univ, Sch Med, John D Dingell VAMC Dept Med, Detroit, MI USA. [Tobi, Martin; Kam, Michael; Ullah, Nadeem; Qureshi, Kashif; Yordanova, Violeta; Hatfield, James; Fligiel, Suzanne E. G.; Sochacki, Paula] Wayne State Univ, Sch Med, John D Dingell VAMC Dept Gastroenterol, Detroit, MI USA. [Tobi, Martin; Kam, Michael; Ullah, Nadeem; Qureshi, Kashif; Yordanova, Violeta; Hatfield, James; Fligiel, Suzanne E. G.; Sochacki, Paula] Wayne State Univ, Sch Med, John D Dingell VAMC Dept Pathol, Detroit, MI USA. [McGarrity, Thomas] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med, Hershey, PA 17033 USA. [Cole, Carolyn; Jacoby, Russell] Univ Wisconsin, Ctr Comprehens Canc, William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Lawson, Michael] Kaiser Permanente, Med Grp, Sacramento, CA USA. RP Tobi, M (reprint author), Philadelphia VAMC, Sect Gastroenterol MED 3GI, Philadelphia, PA 19104 USA. EM martin.tobi@va.gov NR 23 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2008 VL 53 IS 3 BP 723 EP 729 DI 10.1007/s10620-007-9947-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 268HK UT WOS:000253570700018 PM 17934846 ER PT J AU Hewitt, A Hind, J Kays, S Nicosia, M Doyle, J Tompkins, W Gangnon, R Robbins, J AF Hewitt, Angela Hind, Jacqueline Kays, Stephanie Nicosia, Mark Doyle, John Tompkins, Willis Gangnon, Ronald Robbins, JoAnne TI Standardized instrument for lingual pressure measurement SO DYSPHAGIA LA English DT Article DE dysphagia; exercise; sampling rate; tongue strength; tongue pressure; biofeedback; deglutition; deglutition disorders ID SWALLOWING DISORDERS; EXERCISE AB Disease-related atrophy of the tongue muscles can lead to diminished lingual strength and swallowing difficulties. The devastating physical and social consequences resulting from this condition of oropharyngeal dysphagia have prompted investigators to study the effects of tongue exercise in improving lingual strength. We developed the Madison Oral Strengthening Therapeutic (MOST) device, which provides replicable mouth placement, portability, affordability, and a simple user interface. Our study (1) compared the MOST to the Iowa Oral Performance Instrument (IOPI), a commercial pressure-measuring device, and (2) identified the optimal tongue pressure sampling rate for isometric exercises. While initial use of the MOST is focused on evaluating and treating swallowing problems, it is anticipated that its greatest impact will be the prevention of lingual muscle mass and related strength diminishment, which occurs even in the exponentially increasing population of healthy aging adults. C1 [Hewitt, Angela; Hind, Jacqueline; Kays, Stephanie; Nicosia, Mark; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Nicosia, Mark] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. [Gangnon, Ronald] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Doyle, John] Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. [Hewitt, Angela; Hind, Jacqueline; Kays, Stephanie; Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Hewitt, Angela; Tompkins, Willis] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53706 USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace,GRECC 11G, Madison, WI 53705 USA. EM jrobbin2@wisc.edu NR 14 TC 16 Z9 24 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD MAR PY 2008 VL 23 IS 1 BP 16 EP 25 DI 10.1007/s00455-007-9089-0 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 259DN UT WOS:000252919400003 PM 17602265 ER PT J AU Schernhammer, E Ogino, S Fuchs, C AF Schernhammer, E. Ogino, S. Fuchs, C. TI Folate intake and risk of colon cancer in relation to p53 mutational status SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 5th International Conference on Cancer Prevention 2008 CY MAR 06-08, 2008 CL St Gallen, SWITZERLAND SP UICC Global Canc Control, Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, European Assoc Canc Res, European Canc Prevent Org, Amer Canc Soc, Canc Res UK, Swiss Canc League C1 [Schernhammer, E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Schernhammer, E.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Ogino, S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Fuchs, C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2008 VL 6 IS 3 MA P25 BP 49 EP 49 DI 10.1016/S1359-6349(08)70256-8 PG 1 WC Oncology SC Oncology GA 274UJ UT WOS:000254027300063 ER PT J AU Frasca, F Nucera, C Pellegriti, G Gangemi, P Attard, M Stella, M Loda, M Vella, V Giordano, C Trimarchi, F Mazzon, E Belfiore, A Vigneri, R AF Frasca, F. Nucera, C. Pellegriti, G. Gangemi, P. Attard, M. Stella, M. Loda, M. Vella, V. Giordano, C. Trimarchi, F. Mazzon, E. Belfiore, A. Vigneri, R. TI BRAF((V600E)) mutation and the biology of papillary thyroid cancer SO ENDOCRINE-RELATED CANCER LA English DT Article ID BRAF V600E MUTATION; INDEPENDENT CLONAL ORIGIN; GENE-EXPRESSION PROFILES; HURTHLE CELL-CARCINOMA; LYMPH-NODE METASTASIS; DISTINCT TUMOR FOCI; CLINICOPATHOLOGICAL FEATURES; BRAF(V600E) MUTATION; HIGH PREVALENCE; RET ACTIVATION AB BRAF((V600E)) mutation is the most frequent genetic alteration in papillary thyroid carcinomas (PTCs) that are 80-90% of all thyroid cancers. We evaluated the relationship between BRAF((V600E)) and tumor, host, and environmental factors in PTCs from all geographical areas of Sicily. By PCR, BRAF((V600E)) was investigated in a series of 323 PTCs diagnosed in 2002-2005. The correlation between clinicopathological tumor, host, and environmental characteristics and the presence of BRAF((V600E)) were evaluated by both univariate and multivariate analyses. BRAF((V600E)) was found in 38.6% PTCs, with a 52% frequency in the classical PTCs and 26.4% in the tall cell variant. Univariate analysis indicated that BRAF((V600E)) was associated with greater tumor size (P = 0.0048), extra-thyroid invasion (P < 0.0001), and cervical lymph nodal metastases (P = 0.0001). Multivariate logistic regression analysis confirmed that BRAF((V600E)) was an independent predictor of extra-thyroid invasion (P = 0.0001) and cervical lymph nodal metastasis (P = 0.0005). The association between BRAF((V600E)) and extra-thyroid invasion was also found in micro-PTCs (P = 0.006). In 60 classical PTCs, BRAF((V600E)) was positively correlated with matrix metalloproteinase-9 expression (P = 0.0047), suggesting a possible mechanism for BRAF((V600E)) effect on PTC invasiveness. No association was found between BRAF((V600E)) and patient age, gender, or iodine intake. In contrast, a strong association was found with residency in Eastern Sicily (P < 0.0001 compared with Western Sicily). These results indicate that BRAF((V600E)) mutation is a marker of aggressive disease in both micro- and macro-PTCs. Moreover, for the first time, a possible link between BRAF((V600E)) mutation and environmental carcinogens is suggested. C1 [Frasca, F.; Pellegriti, G.; Vella, V.; Vigneri, R.] Univ Catania, Dipartimento Med Interna & Med Specialist, I-95122 Catania, Italy. [Nucera, C.; Trimarchi, F.] Univ Messina, Azienda Osped Univ Policlin, Dipartimento Clin Sperimentale Med & Farmacol, Sez Endocrinol, I-98122 Messina, Italy. [Gangemi, P.] Osped Vittorio Emanuele, Unita Operat Anat Patol, I-95124 Catania, Italy. [Attard, M.] Osped Cervello, Div Endocrinol, I-90146 Palermo, Italy. [Stella, M.] Osped Cervello, Serv Anat Patol, I-90146 Palermo, Italy. [Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Oncol & Ctr Mol Oncol P, Boston, MA 02115 USA. [Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Pathol Dept, Boston, MA 02115 USA. [Giordano, C.] Univ Palermo, Dipartimento Oncol Sperimentale Clin, Sez Endocrinol, I-90127 Palermo, Italy. [Mazzon, E.] Univ Messina, Azienda Osped Univ Policlin, Dipartimento Med Sperimentale & Farmacol, I-98122 Messina, Italy. [Belfiore, A.] Univ Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, Italy. RP Vigneri, R (reprint author), Univ Catania, Dipartimento Med Interna & Med Specialist, PO Garibaldi Nesima,Via Palermo 636, I-95122 Catania, Italy. EM vigneri@unict.it RI Pellegriti, Gabriella/J-7923-2012; OI Giordano, Carla/0000-0003-1731-9395; Vella, Veronica/0000-0002-4968-8550 FU Associazione Italiana per la Ricerca sul Cancro NR 84 TC 119 Z9 127 U1 0 U2 4 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2008 VL 15 IS 1 BP 191 EP 205 DI 10.1677/ERC-07-0212 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 276EB UT WOS:000254123000017 PM 18310287 ER PT J AU Duerr, EM Mizukami, Y Ng, A Xavier, RJ Kikuchi, H Deshpande, V Warshaw, AL Glickman, J Kulke, MH Chung, DC AF Duerr, Eva-Maria Mizukami, Yusuke Ng, Aylwin Xavier, Ramnik J. Kikuchi, Hirotoshi Deshpande, Vikram Warshaw, Andrew L. Glickman, Jonathan Kulke, Matthew H. Chung, Daniel C. TI Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis SO ENDOCRINE-RELATED CANCER LA English DT Article ID PANCREATIC ENDOCRINE TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION; THERAPEUTIC TARGETS; CARCINOID-TUMORS; CYCLIN D1; NEOPLASMS; OVEREXPRESSION; SYSTEM; KINASE AB Current classifications of human gastroenteropancreatic neuroendocrine tumors (NETS) are inconsistent and based upon histopathologic but not molecular features. We sought to compare a molecular classification with the World Health Organization (WHO) histologic classification, identify genes that may be important for tumor progression, and determine whether gastrointestinal NETS (GI-NETs) differ in their molecular profile from pancreatic NETS (PNETs). DNA microarray analysis was performed to identify differentially expressed genes in PNETs and GI-NETs. Confirmation of expression levels was obtained by quantitative real-time PCR. Immunoblotting and mutational analysis were performed for selected genes. Hierarchical clustering of 19 PNETs revealed a 'benign' and 'malignant' cluster that corresponded well with the WHO categories of well-differentiated endocrine tumor (WDET) and well-differentiated endocrine carcinoma (WDEC) respectively. FEV, adenylate cyclase 2 (ADCY2), nuclear receptor subfamily 4, group A, member 2 (NR4A2), and growth arrest and DNA-damage-inducible, beta (GADD45b) were the most highly up-regulated genes in the malignant group of PNETs. Platelet-derived growth factor receptor (PDGFR) was expressed in both WDETs and WDECs, and phosphorylation of PDGFR-beta was observed in 83% of all PNETs. Malignant ileal GI-NETs exhibited a distinctive gene expression profile, and extracellular matrix protein 1 (ECM), vesicular monoamine member 1 (VMAT1), galectin 4 (LGALS4), and RET Proto-oncogene (RET) were highly up-regulated genes. Gene expression profiles reflect the current WHO classification and can distinguish benign from malignant PNETs and also PNETs from GI-NETs. This suggests that molecular profiling may enhance tumor classification schemes. Potential gene targets have also been identified, and PDGFR and RET are candidates that may represent novel therapeutic targets. C1 [Duerr, Eva-Maria; Mizukami, Yusuke; Xavier, Ramnik J.; Kikuchi, Hirotoshi; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Duerr, Eva-Maria; Mizukami, Yusuke; Xavier, Ramnik J.; Kikuchi, Hirotoshi; Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Glickman, Jonathan] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 46 TC 50 Z9 50 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2008 VL 15 IS 1 BP 243 EP 256 DI 10.1677/ERC-07-0194 PG 14 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 276EB UT WOS:000254123000021 PM 18310291 ER PT J AU Jani, N Dewitt, J Eloubeidi, M Varadarajulu, S Appalaneni, V Hoffman, B Brugge, W Lee, K Khalid, A McGrath, K AF Jani, N. Dewitt, J. Eloubeidi, M. Varadarajulu, S. Appalaneni, V. Hoffman, B. Brugge, W. Lee, K. Khalid, A. McGrath, K. TI Endoscopic ultrasound-guided fine-needle aspiration for diagnosis of solid pseudopapillary tumors of the pancreas: a multicenter experience SO ENDOSCOPY LA English DT Article ID EPITHELIAL NEOPLASMS; PAPILLARY; ACCUMULATION; MUTATIONS; CHILDREN AB Background and study alms: Solid pseudopapillary tumors of the pancreas are rare, low-grade, epithelial neoplasms that are usually discovered incidentally in young women. Distinguishing solid pseudopapillary tumors from other pancreatic tumors, especially pancreatic endocrine tumors, can be challenging. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this context remains unclear. The purpose of this study was to describe the endoscopic ultrasound features of solid pseudopapillary tumors and the role of EUS-FNA in the preoperative diagnosis of these tumors. Patients and methods: Patients from five tertiary referral centers with surgically confirmed solid pseudopapillary tumors who had undergone preoperative EUS-FNA were included. The endoscopic ultrasound findings, cytologic descriptions, immunostaining results, operative records, surgical pathology, and results of the most recent clinical follow-up were reviewed. Results: A total of 28 patients were identified (four men [14%], 24 women [86%], mean age +/- standard deviation [SD] 35 +/- 10 years). Solid pseudopapillary tumors had been found as incidental findings on cross-sectional imaging in 50% of cases. The mean tumor size +/- SD was 42 +/- 19.5 mm and the majority were located in the pancreatic body and tail. The endoscopic ultrasound report described a well-defined, echo-poor mass in 86%; the tumors were solid in 14 patients (50%), mixed solid and cystic in 11 patients (39%), and cystic in three patients (11%). A preoperative diagnosis of solid pseudopapillary tumor was made in 21 patients (75%) on the basis of EUS-FNA cytology. Surgical resection was performed in all cases. Laparoscopic resection was performed in eight of these patients (29%). Conclusions: A solid pseudopapillary tumor should be included in the differential diagnosis of any well-demarcated, echo-poor, solid or mixed solid/cystic pancreatic lesion seen during endoscopic ultrasound, particularly in young women. The diagnostic accuracy of EUS-FNA for solid pseudopapillary tumors was 75% in this study. A definitive preoperative diagnosis can guide the surgical approach in selected cases. C1 [Jani, N.; Lee, K.; Khalid, A.; McGrath, K.] UPMC Presbyterian, Pittsburgh, PA 15213 USA. [Dewitt, J.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Eloubeidi, M.; Varadarajulu, S.] Univ Alabama, Sch Med, Birmingham, AL USA. [Appalaneni, V.; Hoffman, B.] Med Univ S Carolina, Charleston, SC 29425 USA. [Brugge, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McGrath, K (reprint author), UPMC Presbyterian, M2,C Wing 200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcgrathk@dom.pitt.edu NR 21 TC 68 Z9 71 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAR PY 2008 VL 40 IS 3 BP 200 EP 203 DI 10.1055/s-2007-995364 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 278PT UT WOS:000254299500005 PM 18067066 ER PT J AU Johnson, JK Barach, P AF Johnson, Julie K. Barach, Paul TI The role of qualitative methods in designing health care organizations SO ENVIRONMENT AND BEHAVIOR LA English DT Article DE qualitative methods; hospital design; observations; focus groups; process mapping AB Qualitative research methodologies can play an important role in health care design as they can provide contextual data about health care settings-specifically the people, processes, and patterns that make up the daily work of providing health care. Health care is provided in complex environments with intricate webs of relationships, which represent the multiple interactions with people, information, technology, culture, and the physical environment in which the care is provided. One could ask, "Is good design possible without an understanding of the context in which the work occurs?" Qualitative methods can capture the experiential aspects of design and usability; however, certain qualitative methods are better suited to capture the complexity of health care. These include observations, focus groups, and interviews, which are discussed in depth. C1 [Johnson, Julie K.] Univ Chicago, Chicago, IL 60637 USA. [Barach, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Barach, Paul] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Johnson, JK (reprint author), Univ Chicago, W216,MC 2007,5841 S Maryland Ave, Chicago, IL 60637 USA. EM jjohnso2@medicine.bsd.uchicago.edu RI Barach, paul/B-9915-2016 OI Barach, paul/0000-0002-7906-698X NR 19 TC 3 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0013-9165 J9 ENVIRON BEHAV JI Environ. Behav. PD MAR PY 2008 VL 40 IS 2 BP 191 EP 204 DI 10.1177/0013916507311547 PG 14 WC Environmental Studies; Psychology, Multidisciplinary SC Environmental Sciences & Ecology; Psychology GA 266SI UT WOS:000253456900003 ER PT J AU Fang, SC Eisen, EA Cavallari, JM Mittleman, MA Christiani, DC AF Fang, Shona C. Eisen, Ellen A. Cavallari, Jennifer M. Mittleman, Murray A. Christiani, David C. TI Acute changes in vascular function among welders exposed to metal-rich particulate matter SO EPIDEMIOLOGY LA English DT Article ID PULSE PRESSURE AMPLIFICATION; HEART-RATE-VARIABILITY; ARTERIAL STIFFNESS; AIR-POLLUTION; AUGMENTATION INDEX; WAVE REFLECTIONS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; APPLANATION TONOMETRY; AMBIENT POLLUTION AB Background: Although welding fume exposure is associated with adverse cardiovascular outcomes, the mechanisms remain unclear. To investigate the role of vascular function, we assessed levels of the augmentation index (a correlate of arterial stiffness) after short-term exposure to welding-derived fine particulate matter (PM2.5). Methods: In a panel study, we monitored 26 male welders over 24 hours on a welding day (n = 25), a nonwelding day (n = 15), or both (n = 14). Augmentation index (expressed as a percent) was obtained in the morning before exposure (baseline) and after exposure in the afternoon and the following morning. Personal PM2.5 exposure was measured over 6 hours of welding or an equivalent nonwelding period. We used linear mixed models adjusting for baseline augmentation index, smoking, age, and time to evaluate the effects of welding (binary) and PM2.5 (continuous) on augmentation index levels. We also assessed modification by welding exposure the day before monitoring (binary). Results: Welding was associated with a 2.8% increase in afternoon augmentation index (95% confidence interval = -1.4 to 7.0) and a 2.4% decrease (-6.9 to 2.2) in next-morning augmentation index. Additional exposure the day prior to monitoring was associated with a greater afternoon increase (5.1%; 0.8 to 9.5). Using PM2.5 concentration, a positive association was observed in the afternoon and an inverse association the next morning; results differed by previous day's welding status after excluding outliers. Conclusions: Subsequent to welding fume exposure, there is an increase in afternoon augmentation index and a decrease in next-morning augmentation index, with greater changes after consecutive days of exposure. These results suggest that exposure to the PM2.5 component of welding fame elicits acute adverse vascular responses. C1 [Fang, Shona C.; Eisen, Ellen A.; Cavallari, Jennifer M.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Mittleman, Murray A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1 Room 1402, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NIEHS NIH HHS [ES009860, ES00002, T32 ES007069]; NIOSH CDC HHS [T42 OH008416] NR 40 TC 25 Z9 26 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 217 EP 225 DI 10.1097/EDE.0b013e31816334dc PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400010 PM 18300696 ER EF