FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shah, GD Kesari, S Xu, RH Batchelor, TT O'Neill, AM Hochberg, FH Levy, B Bradshaw, J Wen, PY AF Shah, GD Kesari, S Xu, RH Batchelor, TT O'Neill, AM Hochberg, FH Levy, B Bradshaw, J Wen, PY TI Comparison of linear and volumetric criteria in assessing tumor response in adult high-grade gliomas SO NEURO-ONCOLOGY LA English DT Article DE malignant glioma; tumor response; RECIST; magnetic resonance imaging ID SOLID TUMORS; MALIGNANT GLIOMA; BRAIN-TUMORS; INTEROBSERVER; SEGMENTATION; RADIOTHERAPY; VARIABILITY; DELINEATION; SURVIVAL; PHASE-2 AB The Response Evaluation Criteria in Solid Tumors, or RECIST criteria (one-dimensional [ID] measurement), are widely used to measure response in tumors, but there are few studies evaluating these criteria in brain tumors. We compared linear and volumetric measurements in adult high-grade supratentorial enhancing gliomas to determine the agreement between measurements, in defining responses and in their subsequent relation to survival. We hypothesized that the ID RECIST criteria maybe suitable for response assessment in adult high-grade gliomas. Tumor size on MRI scans in 104 patients with high-grade enhancing gliomas treated on clinical trial protocols was measured by using 1D (greatest length), 2D (two-dimensional: product of the two longest perpendicular diameters), 3D (three dimensional: product of the longest perpendicular diameters in one plane and the longest orthogonal diameter to that plane), enhancing volume (EV), and total volume (TV). A total of 388 T1 postgadolinium MRI scans (104 baseline and 284 follow-up scans) were evaluated. Volumetric analysis (EV and TV) was performed with commercially available software. Intraobserver and interobserver correlations (rho) were high for all modalities (rho>0.92 and rho>0.71, respectively). Correlation was excellent (rho>0.9) among all modalities except for 3D (rho<0.6). Patient response rates ranged from 12% to 26%. Median progression-free survival (mPFS) and six-month progression-free survival (6mPFS) were not significantly different among the methods (range, 5.3 months to 5.9 months and 42% to 48%, respectively). Landmark analyses of response at two months using linear methods predicted overall survival with hazard ratios of 0.19 to 0.29 (P<0.005). These results suggest high concordance among 1D, 2D, TV, and EV, but not 3D, methods in assessing enhancing tumor progression and in estimating mPFS and 6mPFS in adult brain tumor patients. The tumor response at two months assessed by linear methods correlated better with overall survival. Thus, linear methods are comparable to volumetric methods, but simpler to implement for routine clinical use and for designing clinical trials of brain tumors. C1 Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Canc Inst, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Kesari, Santosh/E-8461-2013 NR 29 TC 96 Z9 97 U1 0 U2 5 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 JAN PY 2006 VL 8 IS 1 BP 38 EP 46 DI 10.1215/S1522851705000529 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 998FW UT WOS:000234305000004 PM 16443946 ER PT J AU Watson, GS Bernhardt, T Reger, MA Cholerton, BA Baker, LD Peskind, ER Asthana, S Plymate, SR Frolich, L Craft, S AF Watson, GS Bernhardt, T Reger, MA Cholerton, BA Baker, LD Peskind, ER Asthana, S Plymate, SR Frolich, L Craft, S TI Insulin effects on CSF norepinephrine and cognition in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; Alzheimer's disease; attention; amnestic mild cognitive impairment; cerebrospinal fluid; insulin; lumbar puncture; norepinephrine; memory ID APOLIPOPROTEIN-E GENOTYPE; LOCUS-COERULEUS; MEMORY; MODULATION; BRAIN AB We assessed the effects of induced hyperinsulinemia on plasma and cerebrospinal fluid (CSF) levels of norepinephrine (NE) and on cognition for patients with Alzheimer's disease (AD) and normal older adults. For normal adults, insulin increased plasma and CSF NE levels; also, recall for paraphrased details of a story improved as CSF NE levels increased. Mental control was positively correlated with CSF levels of NE for patients. These findings demonstrate that raising peripheral insulin levels can modulate CNS NE levels and suggest that insulin-stimulated increases in NE may modulate cognitive functions. (C) 2005 Elsevier Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Heidelberg, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Univ Wisconsin, Sch Med, Ctr Geriatr Res Educ & Clin, William S Middleton Mem Hosp,Dept Med, Madison, WI USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu FU NIA NIH HHS [R01 AG10880, T32 AG000258] NR 16 TC 50 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2006 VL 27 IS 1 BP 38 EP 41 DI 10.1016/j.neurobiolaging.2004.11.011 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 998YM UT WOS:000234355800006 PM 16298239 ER PT J AU Rand-Giovannetti, E Chua, EF Driscoll, AE Schacter, DL Albert, MS Sperling, RA AF Rand-Giovannetti, E Chua, EF Driscoll, AE Schacter, DL Albert, MS Sperling, RA TI Hippocampal and neocortical activation during repetitive encoding in older persons SO NEUROBIOLOGY OF AGING LA English DT Article DE memory; aging; functional magnetic resonance imaging; hippocampus ID INFERIOR PREFRONTAL CORTEX; MILD ALZHEIMERS-DISEASE; FUNCTIONAL-MRI EVIDENCE; AGE-RELATED DIFFERENCES; WORKING-MEMORY; BRAIN ACTIVITY; VISUAL-ATTENTION; SEMANTIC MEMORY; SEX-DIFFERENCES; FRONTAL LOBES AB Episodic memory function is known to decline in the course of normal aging; however, compensatory techniques can improve performance significantly in older persons. We investigated the effects of the memory enhancing technique of repetition encoding on brain activation using event-related functional magnetic resonance imaging (fMRI). Twelve healthy older adults without cognitive impairment were studied with fMRI during repetitive encoding of face-name pairs. During the first encoding trials of face-name pairs that were subsequently remembered correctly, activation of the hippocampus and multiple neocortical regions, including prefrontal, parietal and fusiform cortices, was observed. The second and third encoding trials resulted in continued activation in neocortical regions, but no task-related response within the hippocampus. Functional imaging of successful memory processes thus permits us to detect regionally specific responses in the aging brain. Our findings suggest that hippocampal function is preserved in normal aging and that repetition-based memory enhancing techniques may engage primarily neocortical attentional networks. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Neurol, Ctr Neurocognit Studies, Memory Disorders Unit, Boston, MA 02115 USA. RP Rand-Giovannetti, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM rsperling@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [R01-AG08441, P01-AG-04953]; NIMH NIH HHS [MH60941]; NINDS NIH HHS [K23-NS02189] NR 79 TC 50 Z9 53 U1 8 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2006 VL 27 IS 1 BP 173 EP 182 DI 10.1016/j.neurobiolaging.2004.12.013 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 998YM UT WOS:000234355800020 PM 16298252 ER PT J AU Garcia, ML Singleton, AB Hernandez, D Ward, CM Evey, C Sapp, PA Hardy, J Brown, RH Cleveland, DW AF Garcia, ML Singleton, AB Hernandez, D Ward, CM Evey, C Sapp, PA Hardy, J Brown, RH Cleveland, DW TI Mutations in neurofilament genes are not a significant primary cause of non-SOD1-mediated amyotrophic lateral sclerosis SO NEUROBIOLOGY OF DISEASE LA English DT Article DE ALS; motor neuron diseased; neurofilaments; SOD1; mutation ID MARIE-TOOTH-DISEASE; MOTOR-NEURON DISEASE; MUTANT SUPEROXIDE-DISMUTASE; SUBUNIT-NF-L; MOUSE MODEL; LIGHT GENE; HEAVY GENE; AXONAL NEUROFILAMENTS; SEQUENCE VARIANTS; PERIPHERIN AB While 1 to 2% of amyotrophic lateral sclerosis (ALS) is caused by mutations in the SOD1 gene, the basis of the remaining instances of inherited disease is unknown. Neuropathology, mouse modeling, and human genetics have implicated neurofilaments in the pathogenesis of motor neuron diseases such as ALS and Charcot - Marie- Tooth disease (CMT). A systematic analysis of the coding region and intron-exon boundaries of all three neurofilament genes is now reported from DNA samples derived from more than 200 non-SOD1 linked familial and sporadic ALS patients, along with > 400 non-disease control individuals. Rare variants within each of the three neurofila- ment subunits that are predicted to affect neurofilament assembly properties were identified at higher frequency in non-SOD1 mutant ALS samples. However, none could be unambiguously linked to dominantly inherited disease. Thus, mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in ALS in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes of ALS. Published by Elsevier Inc. C1 Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. NIA, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Boston, MA 02129 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cleveland, DW (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr,CMM-E Room 3072, La Jolla, CA 92093 USA. EM dcleveland@ucsd.edu RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 FU NINDS NIH HHS [R37 NS027036] NR 52 TC 23 Z9 25 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2006 VL 21 IS 1 BP 102 EP 109 DI 10.1016/j.nbd.2005.06.016 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 000KP UT WOS:000234460800011 PM 16084104 ER PT J AU Nguyen, TN Badjatia, N Malhotra, A Gibbons, FK Qureshi, MM Greenberg, SA AF Nguyen, Thanh N. Badjatia, Neeraj Malhotra, Atul Gibbons, Fiona K. Qureshi, Muddasir M. Greenberg, Steven A. TI Factors predicting extubation success in patients with Guillain-Barre syndrome SO NEUROCRITICAL CARE LA English DT Article DE extubation; Guillain-Barre syndrome; mechanical ventilation; vital capacity ID MECHANICAL VENTILATION; RESPIRATORY-FAILURE AB Introduction: Accurate prediction of successful extubation in patients with Guillain-Barre syndrome (GBS) is an important clinical problem. We hypothesized that reversal of clinical indices used to intubate a patient (i.e., declining vital capacity [VC]) predict extubation. Methods: This was a retrospective study in neurocritical care units at two teaching hospitals identifying all mechanically-ventilated patients with GBS. Results: A total of 44 patients with GBS were included. Of these, 14 patients were successfully extubated. There were 10 failed extubations among six patients; and 20 patients underwent tracheostomy without an extubation trial. On the day of extubation, tower negative inspiratory force (NIF) (-50.3 +/- 12.7 versus -28.6 +/- 16.5 cm H2O, p=0.0005) and higher VC (21.9 +/- 8.4 versus 13.0 +/- 5.9 mL/kg, p=0.003) correlated with successful extubation. Change in VC preintubation to preextubation by greater than 4 mL/kg correlated with 82% sensitivity and 90% positive predictive value for successful extubation. Failed extubations were associated with the presence of pulmonary comorbidities (79 versus 36%, p=0.008) and autonomic dysfunction (73 versus 27%, p=0.008). Length of stay (LOS) in the intensive care unit (ICU) was increased in patients who failed extubation and in those patients who underwent tracheostomy (21.5 +/- 11.1 versus 12.5 +/- 8.7, p=0.005). In multivariate analysis, higher VC at extubation was associated with successful extubation (p=0.05). Conclusions: In mechanically-ventilated patients with respiratory failure secondary to GBS, NIF less than -50 cm H2O, and VC improvement preextubation to preintubation by 4 mL/kg were significantly associated with successful extubation. Failed extubation or need for tracheostomy correlated with autonomic dysfunction, pulmonary comorbidities, and prolonged LOS in the ICU. Such parameters may be helpful in identifying patients with GBS likely to succeed extubation versus early referral for tracheostomy. C1 Ctr Hosp Univ Montreal, Dept Med, Serv Neurol, Montreal, PQ, Canada. Ctr Hosp Univ Montreal, Dept Radiol, Montreal, PQ, Canada. Columbia Univ, Med Ctr, Dept Neurol, Div Stroke & Crit Care, New York, NY USA. Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Nguyen, TN (reprint author), Notre Dame Hosp, Dept Radiol, 1560 Sherbrooke St E, Montreal, PQ, Canada. EM thanh00@gmail.com FU NHLBI NIH HHS [R01 HL073146-01, R01 HL073146]; NIA NIH HHS [K23 AG024837, K23 AG024837-03] NR 10 TC 11 Z9 12 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2006 VL 5 IS 3 BP 230 EP 234 DI 10.1385/Neurocrit.Care2006;05:230-234 PG 5 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 132AD UT WOS:000243913200013 PM 17290095 ER PT J AU Schambra, HM Greer, DM AF Schambra, HM Greer, DM TI Asymmetric reversible posterior leukoencephalopathy syndrome SO NEUROCRITICAL CARE LA English DT Article DE reversible posterior leukoencephalopathy; hyperperfusion syndrome; carotid stenosis; vasogenic edema; cerebrovascular autoregulation ID ENCEPHALOPATHY AB Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized radiographically by magnetic resonance imaging as white matter hyperintensities, which reflect cerebral edema. These changes are typically restricted to the parietal and occipital lobes, and are usually quite symmetric. We report a case of asymmetric RPLS involving only one frontal lobe in a patient with severe hypertension, chronic internal carotid artery stenosis, and ipsilateral vasogenic edema. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 8 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2006 VL 4 IS 3 BP 245 EP 247 DI 10.1385/Neurocrit.Care2006;04:245-247 PG 3 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 047HC UT WOS:000237869400010 PM 16757832 ER PT J AU Voss, SE Horton, NJ Tabucchi, THP Folowosele, FO Shera, CA AF Voss, SE Horton, NJ Tabucchi, THP Folowosele, FO Shera, CA TI Posture-induced changes in distortion-product otoacoustic emissions and the potential for noninvasive monitoring of changes in intracranial pressure SO NEUROCRITICAL CARE LA English DT Article DE intracranial pressure; cerebrospinal fluid; intracranial monitor; distortion-product otoacoustic emissions; random effects regression model ID MIDDLE-EAR PRESSURE; INPUT IMPEDANCE; BODY POSITION; BEHAVIOR; COCHLEA; STAPES; CAT AB Introduction: Intracranial pressure (ICP) monitoring is currently an invasive procedure that requires access to the intracrandal space through an opening in the skull. Noninvasive monitoring of ICP via the auditory system is theoretically possible because changes in ICP transfer to the inner ear through connections between the cerebral spinal fluid and the cochlear fluids. In particular, low-frequency distortion-product otoacoustic emissions (DPOAEs), measured noninvasively in the external ear canal, have magnitudes that depend on ICP. Postural changes in healthy humans cause systematic changes in ICP. Here, we quantify the effects of postural changes, and presumably ICP changes, on DPOAE magnitudes. Methods: DPOAE magnitudes were measured on seven normal-hearing, healthy subjects at four postural positions on a tilting table (angles 90 degrees, 0 degrees, - 30 degrees, and - 45 degrees to the horizontal). At these positions, it is expected that ICP varied from about 0 (90 degrees) to 22 mm Hg (-45 degrees). DPOAE magnitudes were measured for a set of frequencies 750 < f(2) < 4000, with f(2)/f(1) = 1.2. Results: For the low-frequency range of 750 <= f(2) <= 1500, the differences in DPOAE magnitude between upright and -45 degrees were highly significant (all p < 0.01), and above 1500 Hz there were minimal differences between magnitudes at 90 degrees versus -45 degrees. There were no significant differences in the DPOAE magnitudes with subjects at 90 degrees and 0 degrees postures. Conclusions: Changes in ICP can be detected using the auditory-based measurement of DPOAEs. In particular, changes are largest at low frequencies. Although this approach does not allow for absolute measurement of ICP, it appears that measurement of DPOAEs may be a useful means of noninvasively monitoring ICP. C1 Smith Coll, Picker Engn Program, Northampton, MA 01063 USA. Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA. EM svoss@email.smith.edu RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NIDCD NIH HHS [R01 DC003687] NR 31 TC 23 Z9 23 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2006 VL 4 IS 3 BP 251 EP 257 DI 10.1385/Neurocrit.Care2006;04:251-257 PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 047HC UT WOS:000237869400012 PM 16757834 ER PT J AU Ruszniewski, P Delle Fave, G Cadiot, G Komminoth, P Chung, D Kos-Kudla, B Kianmanesh, R Hochhauser, D Arnold, R Ahlman, H Pauwels, S Kwekkeboom, DJ Rindi, G AF Ruszniewski, Philippe Delle Fave, Gianfranco Cadiot, Guillaume Komminoth, Paul Chung, Daniel Kos-Kudla, Beata Kianmanesh, Reza Hochhauser, David Arnold, Rudolf Ahlman, Hakan Pauwels, Stanislas Kwekkeboom, Dik J. Rindi, Guido TI Well-differentiated gastric tumors/carcinomas SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st ENETS Consensus Conference on Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors CY NOV, 2005 CL Frascati, ITALY SP European Neuroendocrine Tumor Soc ID ZOLLINGER-ELLISON-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; ARGYROPHIL CARCINOID-TUMORS; PERNICIOUS-ANEMIA; ANTISECRETORY TREATMENT; ATROPHIC GASTRITIS; CELL HYPERPLASIA; BEHAVIOR; ANTRECTOMY; OCTREOTIDE C1 Hop Beaujon, Serv Gastroenterol Pancreatol Pole Maladies Appar, Dept Gastroenterol, F-92118 Clichy, France. Osped S Andrea, Dept Digest & Liver Dis, Rome, Italy. B Claude Bernard Univ, CHU Bichat, Dept Gastroenterol & Hepatol, Paris, France. Kantosspital Baden, Dept Pathol, Baden, Switzerland. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Slaska Univ, Dept Endocrinol, Zabrze, Poland. UFR Bichat Beaujon Louis Mourier Hosp, Dept Surg, Colombes, France. Univ London Royal Free Hosp, Dept Oncol, London NW3 2QG, England. Univ Marburg, Dept Gastroenterol, Marburg, Germany. Univ Gothenburg, Dept Surg, Gothenburg, Sweden. Catholic Univ Louvain, Dept Nucl Med, Brussels, Belgium. Erasmus MC Univ, Dept Nucl Med, Rotterdam, Netherlands. Univ Parma, Dept Pathol & Lab Med, I-43100 Parma, Italy. RP Ruszniewski, P (reprint author), Hop Beaujon, Serv Gastroenterol Pancreatol Pole Maladies Appar, Dept Gastroenterol, F-92118 Clichy, France. EM philippe.ruszniewski@bjn.aphp.fr RI Lopes, Jose Manuel/J-7428-2013; scarpa, aldo/K-6832-2016; FALCHETTI, ALBERTO/Q-1787-2016; OI Lopes, Jose Manuel/0000-0001-8597-3474; scarpa, aldo/0000-0003-1678-739X; FALCHETTI, ALBERTO/0000-0002-6739-4417; Falconi, Massimo/0000-0001-9654-7243; RINDI, Guido/0000-0003-2996-4404; Perren, Aurel/0000-0002-6819-6092; OConnor, Juan Manuel/0000-0002-6975-5466 NR 43 TC 63 Z9 73 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 84 IS 3 BP 158 EP 164 DI 10.1159/000098007 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 140OR UT WOS:000244515600002 PM 17312375 ER PT J AU Howard, VJ Furie, KL Wang, CH Sides, EG Toole, JF AF Howard, Virginia J. Furie, Karen L. Wang, Chin-Hua Sides, Elizabeth G. Toole, James F. TI The changing risk factor profile of participants enrolled in a secondary stroke prevention trial: Vitamin intervention for stroke prevention SO NEUROEPIDEMIOLOGY LA English DT Article DE ischemic stroke; risk factor management; secondary stroke prevention ID TRANSIENT ISCHEMIC ATTACK; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; STATEMENT; ENDARTERECTOMY; HYPERTENSION; COUNCIL; DESIGN; TRENDS AB Objective: To determine if the stroke risk factor profile of participants in a large, multicenter secondary stroke prevention trial changed over the recruitment period. Methods: The 3,680 participants in the Vitamin Intervention for Stroke Prevention (VISP) were categorized into four groups by enrollment date. Baseline patient characteristics and stroke risk factors were compared across groups. Results: Hypertension and hypercholesterolemia management improved but prevalence of three major stroke risk factors did not change. Patients enrolled later had better Mini-Mental State and lower NIH Stroke Scale scores, higher multivitamin use, lower prevalence of cortical infarctions, cardiac symptoms and prior stroke, and lower serum creatinine levels. Conclusions: Those participants enrolled in the later recruitment periods had a different risk factor profile and risk factors were managed differently compared to those enrolled earlier. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Family Hlth Int, Res Triangle Pk, NC USA. Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA. Wake Forest Univ Hlth Sci, Stroke Ctr, Winston Salem, NC USA. RP Howard, VJ (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol, 1665 Univ Blvd, Birmingham, AL 35294 USA. EM vjhoward@uab.edu FU NINDS NIH HHS [R01 NS34447, R01 NS034447] NR 19 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2006 VL 27 IS 4 BP 222 EP 229 DI 10.1159/000096994 PG 8 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 107JD UT WOS:000242166100007 PM 17106212 ER PT J AU Emsley, JG Macklis, JD AF Emsley, Jason G. Macklis, Jeffrey D. TI Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS SO NEURON GLIA BIOLOGY LA English DT Article DE astroglia; CNS atlas; density; GFAP; GFP; morphology; proliferation; S100 beta ID FIBRILLARY ACIDIC PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; GLIAL-CELLS; RAT-BRAIN; REGIONAL HETEROGENEITY; ASTROCYTE HETEROGENEITY; MORPHOLOGICAL HETEROGENEITY; IMMUNOREACTIVE PHENOTYPE; CULTURED ASTROCYTES; SUBVENTRICULAR ZONE AB Astroglia comprise an extremely morphologically diverse cell type that have crucial roles in neural development and function. Nonetheless, distinct regions of the CNS have traditionally been defined by the phenotypic characteristics and connectivity of neurons. In a complementary fashion, we present evidence that discrete regions of the adult CNS can be delineated based solely on the morphology, density and proliferation rates of astroglia. We used transgenic hGFAP-GFP mice in which robust expression of GFP in adult astroglia enables detailed morphological characterization of this diversely heterogeneous cell population with 3D confocal microscopy. By using three complementary methods for labeling adult astroglia (hGFAP-GFP expression, and GFAP and S100 beta immunostaining), we find that there is a remarkably diverse, regionally stereotypical array of astroglial morphology throughout the CNS, and that discrete anatomical regions can be defined solely on the morphology of astroglia within that region. Second, we find that the density of astroglia varies dramatically across the CNS, and that astroglial density effectively delineates even the sub-regions of complex structures, such as the thalamus. We also find that regional astroglial density varies depending on how astroglia are labeled. To quantify and illustrate these broad differences in astroglial density, we generated an anatomical density atlas of the CNS. Third, the proliferation rate, or mitotic index, of astroglia in the adult CNS also effectively defines anatomical regions. These differences are present regardless of the astroglia beta-labeling method used. To supplement our atlas of astroglial density we generated an atlas of proliferation density for the adult CNS. Together, these studies demonstrate that the morphology, density and proliferation rate of astroglia can independently define the discrete cytoarchitecture of the adult mammalian CNS, and support the concept that regional astroglial heterogeneity reflects important molecular and functional differences between distinct classes of astroglia, much like the long-accepted heterogeneity of neuronal populations. C1 Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Massachusetts Gen Hosp, Med Sch,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Neurosci Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Massachusetts Gen Hosp, Med Sch,Dept Neurosurg, Edwards 4 EDR 410 50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NINDS NIH HHS [R01 NS045523, R01 NS045523-04, R01 NS041590, R01 NS049553, R37 NS041590] NR 83 TC 95 Z9 97 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2006 VL 2 BP 175 EP 186 DI 10.1017/S1740925X06000202 PN 3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 154XQ UT WOS:000245542000004 PM 17356684 ER PT J AU Mast, FW Merfeld, DA Kosslyn, SA AF Mast, FW Merfeld, DA Kosslyn, SA TI Visual mental imagery during caloric vestibular stimulation SO NEUROPSYCHOLOGIA LA English DT Article DE high-level vision; occipital cortex; rotation; semicircular canal; sensory interaction ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW PATTERNS; REPRESENTATIONAL HEMINEGLECT; FUNCTIONAL MRI; CORTEX; ROTATION; PET; BRAIN; FMRI; ACTIVATION AB We investigated high-resolution mental imagery and mental rotation, while the participants received caloric vestibular stimulation. High-resolution visual mental imagery tasks have been shown to activate early visual cortex, which is deactivated by vestibular input. Thus, we predicted that vestibular stimulation would disrupt high-resolution mental imagery; this prediction was confirmed. In addition, mental rotation tasks have been shown to activate posterior parietal cortex, which is also engaged in the processing of vestibular stimulation.. As predicted, we also found that mental rotation is impaired during vestibular stimulation. In contrast, such stimulation did not affect performance of a low-imagery control task. These data document previously unsuspected interactions between the vestibular system and the high-level visual system. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA USA. RP Mast, FW (reprint author), Univ Zurich, Dept Psychol, Treichlerstr 10, CH-8032 Zurich, Switzerland. EM f.mast@psychologic.unizh.ch RI Mast, Fred/B-5058-2013 FU NIDCD NIH HHS [R01 DC004158, R01 DC04158]; NIEHS NIH HHS [27300C0032]; NIMH NIH HHS [R01 MH060734, 1 R01 MH60734-01] NR 62 TC 31 Z9 34 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2006 VL 44 IS 1 BP 101 EP 109 DI 10.1016/j.neuropsychologia.2005.04.005 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 004FJ UT WOS:000234737100008 PM 15896815 ER PT J AU Amick, MM Schendan, HE Ganis, G Cronin-Golomb, A AF Amick, MM Schendan, HE Ganis, G Cronin-Golomb, A TI Frontostriatal circuits are necessary for visuomotor transformation: Mental rotation in Parkinson's disease SO NEUROPSYCHOLOGIA LA English DT Article DE visual spatial; parietal cortex; motor imagery; visual object; hemispheric laterality; basal ganglia ID POSITRON-EMISSION-TOMOGRAPHY; DOPAMINERGIC SYSTEM; BASAL GANGLIA; MOTOR; ORIENTATION; REPRESENTATIONS; ACTIVATION; CORTEX; TASK; IDENTIFICATION AB The mental rotation of objects requires visuospatial functions mediated by the parietal lobes, whereas the mental rotation of hands also engages frontal motor-system processes. Nondemented patients with Parkinson's disease (PD), a frontostriatal disorder, were predicted to be impaired on mentally rotating hands. Side of PD motor symptom onset was investigated because the left motor cortices likely have a causal role in hand mental rotation. The prediction was that patients with right-side onset (RPD, greater left-hemisphere dysfunction) would commit more errors rotating hands than patients with left-side onset (LPD). Fifteen LPD, 12 RPD, and 13 normal control adults (NC) made same/different judgments about pairs of rotated objects or hands. There were no group differences with objects. When rotating hands, RPD, but not LPD, made more errors than the NC group. A control experiment evaluated whether visual field of presentation explained differences between PD subgroups. In the first experiment (I A), the hand to be mentally rotated was presented in the right visual field, but here (I B) it was presented in the left visual field. Only the LPD group made more errors than the NC group. The evidence suggests a double dissociation for the RPD and LPD groups between tasks differing in visual-field presentation. The findings indicate that hemifield location of a to-be-rotated hand stimulus can cause the hemispheric frontoparietal networks to be differentially engaged. Moreover, frontostriatal motor systems and the parietal lobes play a necessary role during the mental rotation of hands, which requires integrating visuospatial cognition with motor imagery. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Schendan, HE (reprint author), Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. EM Haline_E.Schendan@tufts.edu OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605 FU NIA NIH HHS [5 F32 AG005914, T32AG00220]; NIMH NIH HHS [5 R01 MH60734-03, R21 MH068610A-01A1, R21 MH66213] NR 44 TC 67 Z9 68 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2006 VL 44 IS 3 BP 339 EP 349 DI 10.1016/j.neuropsychologia.2005.06.002 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 019UG UT WOS:000235861600002 PM 16061263 ER PT J AU Keane, MM Orlando, F Verfaellie, M AF Keane, MM Orlando, F Verfaellie, M TI Increasing the salience of fluency cues reduces the recognition memory impairment in amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE memory; familiarity; recollection ID PERCEPTUAL FLUENCY; TEMPORAL-LOBE; RECALL; FAMILIARITY; DAMAGE; RECOLLECTION; JUDGMENTS; PATIENT; LESIONS; DISSOCIATION AB The present study examined whether the recognition memory deficit in amnesia would be attenuated under conditions that increased the salience of study-induced fluency. Studied and unstudied items were drawn either from separate pools of letters (no-overlap condition) or from the same pool of letters (overlap condition). Study-induced fluency was more salient in the no-overlap than in the overlap condition, because in the no-overlap condition, such fluency occurred at the letter level as well as at the word level. The recognition memory impairment in amnesia was smaller in the no-overlap than in the overlap condition. These findings are consistent with the idea that enhancing the salience of fluency cues promotes reliance on a fluency heuristic that ordinarily is not fully engaged in amnesia, and reduces the recognition memory impairment in amnesia. Crown Copyright (c) 2005 Published by Elsevier Ltd. All rights reserved. C1 Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Keane, MM (reprint author), Wellesley Coll, Dept Psychol, 106 Cent St, Wellesley, MA 02481 USA. EM mkeane@wellesley.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [MH57681, MH70830, R01 MH070830, R01 MH057681] NR 39 TC 17 Z9 17 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2006 VL 44 IS 5 BP 834 EP 839 DI 10.1016/j.neuropsychologia.2005.08.003 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 032YQ UT WOS:000236813200016 PM 16157355 ER PT J AU Slotnick, SD Moo, LR AF Slotnick, Scott D. Moo, Lauren R. TI Prefrontal cortex hemispheric specialization for categorical and coordinate visual spatial memory SO NEUROPSYCHOLOGIA LA English DT Article DE fMRI; item memory; lateralization; perception; source memory; visual memory ID NONSPATIAL WORKING-MEMORY; HUMAN EXTRASTRIATE CORTEX; HUMAN FRONTAL-CORTEX; NEURAL SYSTEMS; FUNCTIONAL-ORGANIZATION; CEREBRAL LATERALIZATION; OBJECT RECOGNITION; EXECUTIVE CONTROL; FUSIFORM CORTEX; EPISODIC MEMORY AB During visual spatial perception of multiple items, the left hemisphere has been shown to preferentially process categorical spatial relationships while the right hemisphere has been shown to preferentially process coordinate spatial relationships. We hypothesized that this hemispheric processing distinction would be reflected in the prefrontal cortex during categorical and coordinate visual spatial memory, and tested this hypothesis using functional magnetic resonance imaging (fMRI). During encoding, abstract shapes were presented in the left or right hemifield in addition to a dot at a variable distance from the shape (with some dots on the shape); participants were instructed to remember the position of each dot relative to the shape. During categorical memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'on' or 'off' of the shape. During coordinate memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'near' or 'far' from the shape (relative to a reference distance). Consistent with our hypothesis, a region in the left prefrontal cortex (BA 10) was preferentially associated with categorical visual spatial memory and a region in the right prefrontal cortex (BA9/10) was preferentially associated with coordinate visual spatial memory. These results have direct implications for interpreting previous findings that the left prefrontal cortex is associated with source memory, as this cognitive process is categorical in nature, and the right prefrontal cortex is associated with item memory, as this process depends on the precise spatial relations among item features or components. (c) 2006 Elsevier Ltd. All rights reserved. C1 Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Slotnick, SD (reprint author), Boston Coll, Dept Psychol, McGuinn Hall, Chestnut Hill, MA 02467 USA. EM sd.slotnick@bc.edu FU NIDCD NIH HHS [DC05068] NR 82 TC 39 Z9 40 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2006 VL 44 IS 9 BP 1560 EP 1568 DI 10.1016/j.neuropsychologia.2006.01.018 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 059ZJ UT WOS:000238770400007 PM 16516248 ER PT J AU Giovanello, KS Keane, MA Verfaellie, M AF Giovanello, Kelly Sullivan Keane, Margaret A. Verfaellie, Mieke TI The contribution of familiarity to associative memory in amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE associative memory; recognition; amnesia; recollection; familiarity; hippocampus; medial temporal lobe; diencephalon ID WERNICKE-KORSAKOFF-SYNDROME; RECOGNITION MEMORY; RECOLLECTIVE EXPERIENCE; HUMAN HIPPOCAMPUS; ITEM RECOGNITION; IMPLICIT MEMORY; SINGLE; INFORMATION; PET; CONSCIOUSNESS AB In Experiment 1, using the remember/know paradigm with control participants, we compared the contribution of recollection and familiarity to associative recognition for compound stimuli and for unrelated word pairs. It was demonstrated that familiarity makes a greater contribution to associative recognition of compound stimuli than to associative recognition of unrelated word pairs. In Experiment 2, we examined associative recognition memory in medial temporal lobe amnesics, diencephalic amnesics, and control participants for the stimuli employed in Experiment 1. Whereas associative recognition for compounds and unrelated words was nearly identical in control participants, associative recognition was higher for compounds than for unrelated word pairs in amnesic patients. This pattern was observed in the medial temporal amnesic group as well as in the diencephalic amnesic group. These results suggest that associative recognition in amnesia is enhanced to the extent that performance can be supported by study-induced familiarity for the studied pair. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. MIT, Athinoula A Martinos Ctr Biomed Imaging, MGH, HMS, Charlestown, MA USA. Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. Boston Univ, Memory Disorders Res Ctr, Sch Med, Boston, MA USA. Boston VA Healthcare Syst, Boston, MA USA. RP Giovanello, KS (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,William James Hall,Rm 860, Cambridge, MA 02138 USA. EM kgio@nmir.mgh.harvard.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [MH57681, F31 MH065113, MH65113, R01 MH057681]; NINDS NIH HHS [NS26985, P50 NS026985] NR 47 TC 61 Z9 62 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2006 VL 44 IS 10 BP 1859 EP 1865 DI 10.1016/j.neuropsychologia.2006.03.004 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 068VS UT WOS:000239403200023 PM 16643967 ER PT J AU Williams, DL Goldstein, G Minshew, NJ AF Williams, DL Goldstein, G Minshew, NJ TI The profile of memory function in children with autism SO NEUROPSYCHOLOGY LA English DT Article DE autism; memory assessment; discriminant analysis; principal components analysis ID PERVASIVE DEVELOPMENTAL DISORDERS; WORKING-MEMORY; IMPAIRED MEMORY; DIAGNOSTIC INTERVIEW; INFANTILE-AUTISM; COMPREHENSION; RECOGNITION; INTACT; FACE; INDIVIDUALS AB A clinical memory test was administered to 38 high-functioning children with autism and 38 individually matched normal controls, 8-16 years of age. The resulting profile of memory abilities in the children with autism was characterized by relatively poor memory for complex visual and verbal information and spatial working memory with relatively intact associative learning ability, verbal working memory, and recognition memory. A stepwise discriminant function analysis of the subtests found that the Finger Windows subtest, a measure of spatial working memory, discriminated most accurately between the autism and normal control groups. A principal components analysis indicated that the factor structure of the subtests differed substantially between the children with autism and controls, suggesting differing organizations of memory ability. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Autism Res Program, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. RP Minshew, NJ (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Autism Res Program, Webster Hall,Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu FU NICHD NIH HHS [HD35469, P01 HD035469, U19 HD035469]; NINDS NIH HHS [R01 NS033355] NR 56 TC 101 Z9 103 U1 1 U2 24 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2006 VL 20 IS 1 BP 21 EP 29 DI 10.1037/0894-4105.20.1.21 PG 9 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 011UK UT WOS:000235293700003 PM 16460219 ER PT J AU Yehuda, R Yang, RK Golier, JA Grossman, RA Bierer, LM Tischler, L AF Yehuda, R Yang, RK Golier, JA Grossman, RA Bierer, LM Tischler, L TI Effect of sertraline on glucocorticoid sensitivity of mononuclear leukocytes in post-traumatic stress disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE sertraline; SSRI; antidepressants; glucocorticoid receptors; lysozyme activity; post-traumatic stress disorder; mononuclear leukocytes ID RECEPTOR FUNCTION; COMBAT VETERANS; P-GLYCOPROTEIN; MESSENGER-RNA; MULTIDRUG-RESISTANCE; ANTIDEPRESSANT DRUGS; MAJOR DEPRESSION; PLASMA-CORTISOL; DEXAMETHASONE; GENE AB This study examined the effects of sertraline (SER) on glucocorticoid sensitivity in mononuclear leukocytes (MNL) from eight subjects with current post-traumatic stress disorder (PTSD) and nine comparison subjects. In all, 60 ml of blood was withdrawn by venipuncture at 0800, and MNL were isolated from blood and divided into two portions: the first contained live cells incubated with a series of concentrations of dexamethasone (DEX); the second contained cells incubated with similar concentrations of DEX+2 mu M SER. Group difference in the concentrations of DEX required to inhibit lysozyme activity by 50% were evaluated under conditions of DEX-only and DEX+SER using analysis of covariance (ANCOVA). A significant Group x Condition interaction reflected that SER altered the lysozyme IC50-DEX in the direction of decreasing sensitivity to glucocorticoids in PTSD while having no uniform effect in cells from comparison subjects. The data provide support for the idea that glucocorticoid receptors might be more responsive to antidepressants in PTSD than in persons without PTSD. Insofar as increased sensitivity to glucocorticoids has been linked with PTSD, the actions of SER on the lysozyme IC50-DEX suggest that this medication may target a biologic alteration associated with PTSD pathophysiology. C1 Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Yehuda, R (reprint author), Bronx Vet Affairs, Psychiat 116A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov NR 53 TC 15 Z9 15 U1 5 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2006 VL 31 IS 1 BP 189 EP 196 DI 10.1038/sj.npp.1300862 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 023MX UT WOS:000236132000019 PM 16123752 ER PT J AU Minzenberg, MJ Grossman, R New, AS Mitropoulou, V Yehuda, R Goodman, M Reynolds, DA Silverman, JM Coccaro, EF Marcus, S Siever, LJ AF Minzenberg, MJ Grossman, R New, AS Mitropoulou, V Yehuda, R Goodman, M Reynolds, DA Silverman, JM Coccaro, EF Marcus, S Siever, LJ TI Blunted hormone responses to ipsapirone are associated with trait impulsivity in personality disorder patients SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; 5-HT1A receptor; cortisol; prolactin; impulsivity; borderline personality disorder ID POSITRON-EMISSION-TOMOGRAPHY; 5-HT1A RECEPTOR FUNCTION; META-CHLOROPHENYLPIPERAZINE; SEROTONIN RECEPTORS; AGGRESSIVE-BEHAVIOR; TOURETTES-SYNDROME; ANXIETY DISORDERS; DEPRESSION; CORTISOL; CHALLENGE AB Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT1A receptor in this behavior. We tested the hypothesis that central 5-HT1A receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT1A receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D-2 receptor dysfunction may play a role in impulsivity, whereas 5-HT1A cell-body autoreceptor function may be spared in these disorders. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, OOMH, Dept Psychiat, Bronx, NY 10468 USA. Baystate Med Ctr, Dept Psychiat, Springfield, MA USA. Univ Chicago, Pritzker Sch Med, Dept Psychiat, Chicago, IL 60637 USA. Mt Sinai Sch Med, Dept Biomath, New York, NY USA. RP Minzenberg, MJ (reprint author), Bronx Vet Affairs Med Ctr, OOMH, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.minzenberg@mssm.edu FU NIMH NIH HHS [R01-MH56606-01A2]; PHS HHS [R03 MR 5869701] NR 47 TC 11 Z9 11 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2006 VL 31 IS 1 BP 197 EP 203 DI 10.1038/sj.npp.1300853 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 023MX UT WOS:000236132000020 PM 16123761 ER PT J AU Taub, E Uswatte, G AF Taub, Edward Uswatte, Gitendra TI Constraint-Induced Movement therapy: Answers and questions after two decades of research SO NEUROREHABILITATION LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIAL; UPPER EXTREMITY; LEARNED NONUSE; CHRONIC STROKE; FORCED USE; REHABILITATION AB Constraint-Induced Movement therapy or CI therapy is a behavioral approach to neurorehabilitation based on a program of neuroscience experiments conducted with deafferented monkeys. Over the last 20 years, a large body of evidence has accumulated to support the efficacy of CI therapy for rehabilitating hemiparetic arm use in individuals with chronic stroke. Given the persuasive evidence for its efficacy to date, other research questions have risen to the forefront. How cost-effective is CI therapy? What are optimal training and other treatment parameters? What patient characteristics moderate the effects of CI therapy? The papers gathered in this special issue address many of these topics. C1 Univ Alabama, Sch Social & Behav Sci, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Sch Hlth Related Profess, Dept Phys Therapy, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Taub, E (reprint author), Univ Alabama, Sch Social & Behav Sci, Dept Psychol, 1530 3rd Ave S,CPM712, Birmingham, AL 35294 USA. EM etaub@uab.edu RI Uswatte, Gitendra/C-4913-2009 FU NICHD NIH HHS [HD34273] NR 18 TC 51 Z9 52 U1 0 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2006 VL 21 IS 2 BP 93 EP 95 PG 3 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 076WP UT WOS:000239989200001 PM 16917156 ER PT J AU Mennemeyer, ST Taub, E Uswatte, G Pearson, S AF Mennemeyer, Stephen T. Taub, Edward Uswatte, Gitendra Pearson, Sonya TI Employment in households with stroke after Constraint-Induced Movement therapy SO NEUROREHABILITATION LA English DT Article DE stroke; rehabilitation; cost benefit analysis; employment ID UPPER-EXTREMITY; REHABILITATION; CARE; RELIABILITY; MORTALITY; AUTOCITE; VALIDITY; PATIENT; HEALTH; FAMILY AB Randomized controlled clinical studies show that Constraint-Induced Movement therapy ( CI therapy) improves impaired arm function in patients with stroke. Little is known about how this therapy affects employment of patients or their caregivers. Individuals more than 1-year post-stroke ( N = 121) were retrospectively surveyed about their activities and employment prior to stroke, after stroke but before CI therapy and after CI therapy. They were also asked if someone had stopped working to be a caregiver and if that person had resumed employment. Before stroke, 48% of patients had been employed; this fell to 22% after stroke and did not significantly rise after CI therapy with most of the newly unemployed moving into a permanent retirement status before starting CI therapy. Among the CI therapy patients, one-quarter ( 29/121) reported that someone had limited their employment to take care of them following their stroke. After CI therapy, more than 60% ( 18/29) of caregivers returned to employment. Our preliminary finding regarding return to work by caregivers of stroke patients post-CI therapy warrants further study using prospective methods and randomized, controlled designs. C1 Univ Alabama, Sch Publ Hlth, Dept Hlth Care Org & Policy, Birmingham, AL 35294 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Mennemeyer, ST (reprint author), Univ Alabama, Sch Publ Hlth, Dept Hlth Care Org & Policy, 330 RPHB,1530 3rd Ave S, Birmingham, AL 35294 USA. EM smenneme@uab.edu RI Uswatte, Gitendra/C-4913-2009 FU NICHD NIH HHS [HD 34273, R01 HD034273] NR 32 TC 6 Z9 6 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2006 VL 21 IS 2 BP 157 EP 165 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 076WP UT WOS:000239989200007 PM 16917162 ER PT J AU Niquet, J Seo, DW Allen, SG Wasterlain, CG AF Niquet, J. Seo, D. -W. Allen, S. G. Wasterlain, C. G. TI Hypoxia in presence of blockers of excitotoxicity induces a caspase-dependent neuronal necrosis SO NEUROSCIENCE LA English DT Article DE apoptosis; cytochrome c; MK-801; NBQX; ATP; mitochondrial membrane potential ID TRANSIENT CEREBRAL-ISCHEMIA; D-ASPARTATE RECEPTORS; CELL-DEATH; MOLECULAR-MECHANISMS; CYTOCHROME-C; BRAIN-INJURY; APOPTOSIS; INHIBITION; ACTIVATION; GLUTAMATE AB When excitotoxic mechanisms are blocked, severe or prolonged hypoxia and hypoxia-ischemia can still kill neurons, by a mechanism which is poorly understood. We studied this "non-excitotoxic hypoxic death" in primary cultures of rat dentate gyrus neurons. Many neurons subjected to hypoxia in the presence of blockers of ionotropic glutamate receptors developed the electron microscopic features of necrosis. They showed early mitochondrial swelling, loss of mitochondrial membrane potential and cytoplasmic release of cytochrome c, followed by activation of caspase-9, and by caspase-9-dependent activation of caspase-3. Caspase inhibitors were neuroprotective. These results suggest that "nonexcitotoxic hypoxic neuronal death" requires the activation in many neurons of a cell death program originating in mitochondria and leading to necrosis. Published by Elsevier Ltd on behalf of IBRO. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Sungkyunkwan Univ, Sch Med, Dept Neurol, Samsung Med Ctr, Seoul, South Korea. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU NINDS NIH HHS [NS13515] NR 24 TC 11 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 141 IS 1 BP 77 EP 86 DI 10.1016/j.neuroscience.2006.03.073 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 063PZ UT WOS:000239033300009 PM 16697116 ER PT J AU Barton, JJS Kuzin, A Polli, F Manoach, DS AF Barton, JJS Kuzin, A Polli, F Manoach, DS TI The use of working memory for task prediction: What benefits accrue from different types of foreknowledge? SO NEUROSCIENCE LA English DT Article DE working memory; foreknowledge; saccade; prediction; task-switch ID SUPPLEMENTARY MOTOR AREA; SACCADIC EYE-MOVEMENTS; SET RECONFIGURATION; HUNTINGTONS-DISEASE; NEURONAL-ACTIVITY; EXPRESS SACCADES; REACTION-TIME; PREDICTABILITY; SCHIZOPHRENIA; COSTS AB The assumption that the deployment of executive processes invariably improves task performance is implicit to cognitive theory. In particular, working memory can be used to retain and update historical information about predictable trial sequences (foreknowledge) so that subjects can anticipate and prepare for the upcoming trial more effectively. We review the effects of different types of foreknowledge on response accuracy and latency, particularly in relation to experiments investigating saccadic eye movements in humans. While it is possible to make all aspects of an impending trial predictable, varying the predictability of different components of the trial independently can reveal which cognitive operations are potentially modifiable by foreknowledge. These operations include stimulus processing, retrieval of task-set rules, and response preparation, among others. The available data suggest that, while response preparation can be completed and the response even executed before the stimulus appears (i.e. anticipation) when the subject possesses complete task-foreknowledge (knowing both the stimulus to appear and the response required), foreknowledge of the task-set alone does not permit advance configuration of the task-set rules. A taxonomy for foreknowledge is proposed, including foreknowledge for timing, stimulus, set, response, and task. Work on differentiating these effects in neurophysiology, neuroimaging, and neuropsychology is still in the early stages. (C) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Univ British Columbia, Dept Neurol, VGH Eye Care Ctr, Sect D, Vancouver, BC V5Z 3N9, Canada. Univ British Columbia, Dept Ophthalmol & Visual Sci, VGH Eye Care Ctr, Sect D, Vancouver, BC V5Z 3N9, Canada. Univ British Columbia, Dept Neuroophthalmol, VGH Eye Care Ctr, Sect D, Vancouver, BC V5Z 3N9, Canada. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Barton, JJS (reprint author), Univ British Columbia, Dept Neurol, VGH Eye Care Ctr, Sect D, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012 NR 51 TC 9 Z9 11 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 139 IS 1 BP 385 EP 392 DI 10.1016/j.neuroscience.2005.10.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 035BZ UT WOS:000236976300033 PM 16326018 ER PT J AU Wink, MR Braganhol, E Tamajusuku, ASK Lenz, G Zerbini, LF Libermann, TA Sevigny, J Battastini, AMO Robson, SC AF Wink, MR Braganhol, E Tamajusuku, ASK Lenz, G Zerbini, LF Libermann, TA Sevigny, J Battastini, AMO Robson, SC TI Nucleoside triphosphate diphosphohydrolase-2 (NTPdase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes SO NEUROSCIENCE LA English DT Article DE ATP; ecto-ATPase; E-NTPDase family; NTPDase2; CD39L1; astrocytes ID ECTO-ATP-DIPHOSPHOHYDROLASE; EXTRACELLULAR ADENINE-NUCLEOTIDES; GLIAL-CELLS; BACTERIAL EXPRESSION; BRAIN; APYRASE; CD39L4; IDENTIFICATION; METABOLISM; RECEPTORS AB Inflammatory and degenerative pathophysiological processes within the CNS are important causes of human disease. Astrocytes appear to modulate these reactions and are a major source of inflammatory mediators, e.g. extracellular adenine nucleotides, in nervous tissues. Actions following extracellular nucleotides binding to type 2 purinergic receptors are regulated by ectonucleotidases, including members of the CD39/ecto-nucleoside triphosphate diphosphohydrolase family. The ectonucleotidases of astrocytes expressed by rat brain rapidly convert extracellular ATP to ADP, ultimately to AMP. RT-PCR, immunocytochemistry as well as Western blotting analysis demonstrated expression of multiple ecto-nucleoside triphosphate diphosphohydrolase family members at both the mRNA and protein level. By quantitative real-time PCR, we identified Entpd2 (CD39L1) as the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar astrocytes. These data in combination with the elevated ecto-ATPase activity observed in these brain regions, suggest that NTPDase2, an ecto-enzyme that preferentially hydrolyzes ATP, is the major ecto-nucleoside triphosphate diphosphohydrolase expressed by rat astrocytes. NTPDase2 may modulate inflammatory reactions within the CNS and could represent a useful therapeutic target in human disease. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. CHU Laval, Ctr Rech Rhumatol & Immunol, Laval, PQ, Canada. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02215 USA. Univ Fed Rio Grande Sul, Dept Biofis Biociencias, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Bioquim, Inst Ciencias Basicas Saude, BR-90035003 Porto Alegre, RS, Brazil. RP Battastini, AMO (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 99 Brookline Ave, Boston, MA 02215 USA. EM baltas@terra.com.br; srobson@bidmc.harvard.edu RI Lenz, Guido/A-7618-2008; Libermann, Towia/F-9866-2010; Sevigny, Jean/E-8039-2012; Braganhol, Elizandra/C-6439-2013; Zerbini, Luiz /B-7720-2015; OI Sevigny, Jean/0000-0003-2922-1600; Libermann, Towia/0000-0002-4006-8179 FU Canadian Institutes of Health Research [49460]; NHLBI NIH HHS [HL-57307, HL-63972] NR 57 TC 68 Z9 68 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 138 IS 2 BP 421 EP 432 DI 10.1016/j.neuroscience.2005.11.039 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 022HL UT WOS:000236046100007 PM 16414200 ER PT J AU Broekman, MLD Comer, LA Hyman, BT Siena-Esteves, M AF Broekman, MLD Comer, LA Hyman, BT Siena-Esteves, M TI Adeno-associated virus vectors serotyped with AAV8 capsid are more efficient than AAV-1 or-2 serotypes for widespread gene delivery to the neonatal mouse brain SO NEUROSCIENCE LA English DT Article DE adeno-associated virus; serotypes; AAV8; brain; gene delivery; neonatal ID CONVECTION-ENHANCED DELIVERY; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; LIVER TRANSDUCTION; MAMMALIAN BRAIN; VIRAL VECTORS; TYPE-2 VECTOR; CO-INFUSION; IN-VIVO; EXPRESSION AB Adeno-associated virus (AAV) vectors have gained a preeminent position in the field of gene delivery to the normal brain through their ability to achieve extensive transduction of neurons and to mediate long-term gene expression with no apparent toxicity. In adult animals direct infusion of AAV vectors into the brain parenchyma results in highly efficient transduction of target structures. However AAV-mediated global delivery to the adult brain has been an elusive goal. In contrast, widespread global gene delivery has been obtained by i.c.v. injection of AAV1 or AAV2 in neonates. Among the novel AAV serotypes cloned and engineered for production of recombinant vectors, AAV8 has shown a tremendous potential for in vivo gene delivery with nearly complete transduction of many tissues in rodents after intravascular infusion. Here we compare the efficiency of an AAV8 serotyped vector with that of AAV1 and AAV2 serotyped vectors for the extent of gene delivery to the brain after neonatal injection into the lateral ventricles. The vectors all encoded green fluorescent protein (GFP) under control of a hybrid CMV enhancer/chicken beta-actin promoter with AAV2 inverted terminal repeats, but differed from each other with respect to the capsid type. A total of 6.8 x 10(10) genome copies were injected into the lateral ventricles of postnatal day 0 mice. Mice were killed at postnatal day 30 and brains analyzed for distribution of GFP-positive cells. AAV8 proved to be more efficient than AAV1 or AAV2 vectors for gene delivery to all of the structures analyzed, including the cerebral cortex, hippocampus, olfactory bulb, and cerebellum. Moreover the intensity of gene expression, assessed using a microarray reader, was considerably higher for AAV8 in all structures analyzed. In conclusion, the enhanced transduction achieved by AAV8 compared with AAV1 and AAV2 indicates that AAV8 is the superior serotype for gene delivery to the CNS. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neurosci Program, Charlestown, MA 02129 USA. Univ Utrecht, Med Ctr, Dept Pharmacol & Anat, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Siena-Esteves, M (reprint author), Mol Neurogenet Unit, Room 6309,149 13th St, Charlestown, MA 02129 USA. EM msesteves@partners.org FU NIA NIH HHS [AG08487] NR 51 TC 120 Z9 123 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 138 IS 2 BP 501 EP 510 DI 10.1016/j.neurosceince.2005.11.057 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 022HL UT WOS:000236046100013 PM 16414198 ER PT J AU Lauriat, TL Dracheva, S Chin, B Schmeidler, J McInnes, LA Haroutunian, V AF Lauriat, TL Dracheva, S Chin, B Schmeidler, J McInnes, LA Haroutunian, V TI Quantitative analysis of glutamate transporter mRNA expression in prefrontal and primary visual cortex in normal and schizophrenic brain SO NEUROSCIENCE LA English DT Article DE quantitative PCR; EAAT2; GLT1; gene expression; antipsychotic; RT-PCR ID AMINO-ACID TRANSPORTER; IN-SITU HYBRIDIZATION; RAT CEREBRAL-CORTEX; AMYOTROPHIC-LATERAL-SCLEROSIS; 2 SPLICE VARIANTS; GENE-EXPRESSION; ELDERLY-PATIENTS; COMPARATIVE IMMUNOCYTOCHEMISTRY; RECEPTOR EXPRESSION; ALZHEIMERS-DISEASE AB Abnormalities of the glutamatergic system in schizophrenia have been identified in numerous studies, but little is known about the role of glutamate transporters and their messenger RNA (mRNA) expression. In addition, the abundances of the two major isoforms of human excitatory amino acid transporter 2 (EAAT2) or its rat ortholog, glutamate transporter 1, have never been compared in a quantitative manner. Using quantitative reverse transcription-polymerase chain reaction, we established that the expression of the EAAT1, EAAT2a, EAAT2b, and EAAT3 transcripts was not different in the dorsolateral prefrontal and primary visual cortices of persons with schizophrenia relative to matched controls. EAAT2a expression was about 25-fold and 10-fold higher than EAAT2b in human and rat brain, respectively. The data provided no evidence of an effect of antipsychotic medications on the mRNA expression of the glutamate transporters. However, because most of the schizophrenic subjects in the cohort had been treated with antipsychotics for many years, it is still possible that changes in transporter expression were masked by medication effects. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Biomath, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu OI Lauriat, Tara/0000-0003-0729-9386 NR 73 TC 23 Z9 26 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 137 IS 3 BP 843 EP 851 DI 10.1016/j.neuroscience.2005.10.003 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 009OG UT WOS:000235121000011 PM 16297566 ER PT J AU Burgio, KL Goode, PS Richter, HE Locher, JL Roth, DL AF Burgio, Kathryn L. Goode, Patricia S. Richter, Holly E. Locher, Julie L. Roth, David L. TI Global ratings of patient satisfaction and perceptions of improvement with treatment for urinary incontinence: Validation of three global patient ratings SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE behavior therapy; outcomes assessment; patient satisfaction; urinary incontinence; validation study ID RANDOMIZED CONTROLLED-TRIAL; AUTOLOGOUS FASCIA LATA; OLDER WOMEN; LONG-TERM; DISSATISFACTION; QUESTIONNAIRES; SERVICES; EFFICACY; SUCCESS AB Aims: To test the validity of three patient global ratings, satisfaction, perception of improvement, and estimated percent improvement, for measuring outcomes of behavioral treatment for urinary incontinence. Methods: This report is a secondary analysis of data from three randomized controlled trials testing behavioral interventions for incontinence. Participants were 359 community-dwelling women, aged 40-92 years, with stress, urge, or mixed urinary incontinence. All participants received an 8-week program of clinic-based or self-administered behavioral training. Subjective outcomes included a patient satisfaction question (PSQ), global perception of improvement (GPI), and estimated percent improvement (EPI). Convergent validity was tested by examining the relationship between each measure and reduction of incontinence (bladder diary), change on the incontinence impact questionnaire (IIQ), and desire for another treatment. Discriminant validity was explored by examining the relationship of the global ratings to five measures not expected to be related to outcome (age, race, BMI, education level, and change in perceived pain). Results: All three patient global ratings were significantly associated with each other (P < 0.0001), with diary measures of reduction of incontinence episodes (P < 0.0001), and change in the IIQ (P < 0.005), and inversely associated with desire for another treatment (P < 0.0001). All three patient ratings were not significantly associated with age, race, BMI, education level, or change in perceived pain. Conclusion: Patient global ratings of satisfaction, perception of improvement, and estimated percent improvement. have acceptable convergent and discriminant validity for measuring outcomes in studies of behavioral treatment for urinary incontinence. C1 Birmingham Atlanta GRECC, Dept Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Alabama, Ctr Aging, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, GRECC, 11G,700 19th St S, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu FU NIA NIH HHS [AG R01 08010]; NIDDK NIH HHS [R01 DK49472]; PHS HHS [KO4 00431] NR 32 TC 63 Z9 63 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2006 VL 25 IS 5 BP 411 EP 417 DI 10.1002/nau.20243 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 073TD UT WOS:000239764600003 PM 16652380 ER PT S AU Reusch, JEB Watson, PA Pugazhenthi, S AF Reusch, Jane E. B. Watson, Peter A. Pugazhenthi, Subbiah BE Friedman, JE TI Disruption of CREB regulated of gene expression in diabetes SO NEW TRANSCRIPTION FACTORS AND THEIR ROLE IN DIABETES AND ITS THERAPY SE Advances in Molecular and Cellular Endocrinology LA English DT Article; Book Chapter ID SMOOTH-MUSCLE-CELLS; ELEMENT-BINDING PROTEIN; CAMP-RESPONSE ELEMENT; FACTOR-ALPHA-RECEPTOR; ARTERIAL-WALL THICKNESS; PANCREATIC BETA-CELLS; GROWTH-FACTOR; TRANSCRIPTION FACTOR; CYCLIC-AMP; IN-VIVO AB Cardiovascular disease it is the leading cause of death in diabetes. In light of this, diabetes has recently been named and a cardiovascular disease equivalent. The molecular mechanisms that place persons with diabetes at excess vascular risk are numerous, including dyslipidemia, hypertension, hyperglycemia chronic inflammation and oxidative stress. These different factors place the diabetic vasculature in a state of chronic metabolic stress and this stress leads to vascular dysfunction. Our laboratory has focused on gaining a better understanding of the impact of diabetes and insulin resistance (IR) upon vascular smooth muscle cell gene regulation. Specifically, we have observed that the transcription factor CREB (cAMP response element binding protein) is critical for the maintenance of healthy quiescent (contractile and non-proliferative) vascular smooth muscle cell (SMC) function. In rodent models of diabetes and IR there is decreased expression of CREB protein in the vasculature. Loss of vascular CREB expression is associated with simultaneous increased expression of pro-atherogenic transcriptional regulators, such as NF-kB and C/EBP delta (CCAAT enhancer binding protein). This imbalance promotes SMC activation (proliferation, migration, matrix production and apoptosis) and may be important for excess vascular disease in diabetes. The evidence for CREB regulation of SMC function and its disruption in models of diabetes and atherosclerosis will be discussed in this chapter. In addition to macrovascular disease, many other target organs are injured by the metabolic stress of diabetes including pancreatic beta cells (which contribute to disease progression) and cardiac and neuronal cells (which contribute to complications). We have identified a pattern of changes in gene regulation, loss of CREB function and augmentation of stress induced gene expression, that may contribute to the multi-organ dysfunction observed in diabetes. C1 [Reusch, Jane E. B.; Watson, Peter A.; Pugazhenthi, Subbiah] Univ Colorado, Hlth Sci Ctr, Vet Affairs Med Ctr, Div Endocrinol, Denver, CO 80202 USA. [Reusch, Jane E. B.; Watson, Peter A.] Denver VA Med Ctr, Denver, CO USA. RP Reusch, JEB (reprint author), Univ Colorado, Hlth Sci Ctr, Vet Affairs Med Ctr, Div Endocrinol, Denver, CO 80202 USA. NR 96 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER NORTH HOLLAND PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-2566 BN 978-0-08-046355-1 J9 ADV MOL CELL ENDOCR PY 2006 VL 5 BP 211 EP 231 DI 10.1016/S1569-2566(06)05011-3 PG 21 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BCV16 UT WOS:000311560500012 ER PT S AU Pihlajamaki, J Patti, ME AF Pihlajamaeki, Jussi Patti, Mary Elizabeth BE Friedman, JE TI Regulation of PGC-1 in humans with insulin resistance and type 2 diabetes: Functional implications SO NEW TRANSCRIPTION FACTORS AND THEIR ROLE IN DIABETES AND ITS THERAPY SE Advances in Molecular and Cellular Endocrinology LA English DT Article; Book Chapter ID PROLIFERATOR-ACTIVATED RECEPTOR; HUMAN SKELETAL-MUSCLE; ALPHA ERR-ALPHA; HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; IMPAIRED GLUCOSE-TOLERANCE; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; PPAR-GAMMA COACTIVATOR-1; BODY-MASS INDEX; GENE-EXPRESSION; MITOCHONDRIAL BIOGENESIS AB The PGC-1 family of coactivator genes has emerged as attractive candidates for type 2 diabetes (T2DM) diabetes for several reasons: (1) they play a central role in regulating expression of genes critical for maintenance of metabolic homeostasis and oxidative metabolism in key target tissues, and (2) expression of PGC-1 and mitochondrial oxidative genes is reduced in skeletal muscle and adipose tissue from humans with diabetes and "prediabetes." In turn, this expression phenotype may be linked to both primary sequence alterations and environmental risk factors for diabetes, including overnutrition, obesity, and inactivity. We postulate that in genetically susceptible individuals, the development of obesity and decreased aerobic capacity due to inactivity may act in concert to reduce PGC-1 expression, contributing to impaired oxidative metabolism and accumulation of lipid in key insulin target tissues, thus increasing diabetes risk. In this chapter, we review the data supporting a potential role for PGC-1 family members as integrators between genetic and environmental risk factors at a molecular level and thus contributors to pathogenesis of T2DM. C1 [Pihlajamaeki, Jussi; Patti, Mary Elizabeth] Harvard Univ, Joslin Diabet Ctr, Div Res, Sch Med, Boston, MA 02215 USA. RP Pihlajamaki, J (reprint author), Harvard Univ, Joslin Diabet Ctr, Div Res, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. NR 144 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER NORTH HOLLAND PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-2566 BN 978-0-08-046355-1 J9 ADV MOL CELL ENDOCR PY 2006 VL 5 BP 233 EP 253 DI 10.1016/S1569-2566(06)05012-5 PG 21 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BCV16 UT WOS:000311560500013 ER PT B AU Cascio, EW AF Cascio, Ethan W. GP IEEE TI The use of the compensated contoured double scatterer in the radiation test beamline at the Francis H. Burr Proton Therapy Center SO NSREC: 2006 IEEE Radiation Effects Data Workshop, Workshop Record LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop CY JUL 17-21, 2006 CL Ponte Vedra Beach, FL SP IEEE Nucl & Plasma Sci Soc DE contoured scatterer; proton beam; proton therapy; radiation testing AB The compensated contoured double scatterer is a beam spreading system that was originally developed for clinical proton therapy applications. The application of this system to radiation test beams at the Francis H. Burr Proton Therapy Center is described. C1 Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0638-8 PY 2006 BP 177 EP 182 PG 6 WC Nuclear Science & Technology SC Nuclear Science & Technology GA BFX09 UT WOS:000245236500030 ER PT J AU Turlure, F Maertens, G Rahman, S Cherepanov, P Engelman, A AF Turlure, F Maertens, G Rahman, S Cherepanov, P Engelman, A TI A tripartite DNA-binding element, comprised of the nuclear localization signal and two AT-hook motifs, mediates the association of LEDGF/p75 with chromatin in vivo SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRESS-RELATED GENES; HIV-1 INTEGRASE; GROWTH-FACTOR; PWWP DOMAIN; TRANSCRIPTIONAL COACTIVATORS; PREINTEGRATION COMPLEXES; MYELOID-LEUKEMIA; CDNA INTEGRATION; HUMAN-CELLS AB Lens epithelium-derived growth factor p75 (LEDGF/p75) is a DNA-binding, transcriptional co-activator that participates in HIV-1 integration site targeting. Using complementary approaches, we determined the mechanisms of LEDGF/p75 DNA-binding in vitro and chromatin-association in living cells. The binding of highly-purified, recombinant protein was assayed by surface plasmon resonance (SPR) and electrophoretic mobility gel shift. Neither assay revealed evidence for sequence-specific DNA-binding. Residues 146-197 spanning the nuclear localization signal (NLS) and two AT-hook motifs mediated non-specific DNA-binding, and DNA-binding deficient mutants retained the ability to efficiently stimulate HIV-1 integrase activity in vitro. Chromatin-association was assessed by visualizing the localization of EGFP fusion proteins in interphase and mitotic cells. Although a conserved N-terminal PWWP domain was not required for binding to condensed mitotic chromosomes, its deletion subtly affected the nucleoplasmic distribution of the protein during interphase. A dual AT-hook mutant associated normally with chromatin, yet when the mutations were combined with NLS changes or deletion of the PWWP domain, chromatin-binding function was lost. As the PWWP domain did not readily bind free DNA in vitro, our results indicate that chromatin-association is primarily affected through DNA-binding, with the PWWP domain likely contributing a protein interaction to the overall affinity of LEDGF/p75 for human chromatin. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI Cherepanov, Peter/F-6859-2010; Maertens, Goedele/D-8628-2015 OI Cherepanov, Peter/0000-0002-0634-538X; Maertens, Goedele/0000-0002-1963-8026 FU NIAID NIH HHS [AI60354, AI39394, AI52014, P30 AI060354, R01 AI039394, R01 AI052014, R37 AI039394] NR 55 TC 84 Z9 85 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 5 BP 1653 EP 1665 DI 10.1093/nar/gkl052 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027RL UT WOS:000236432900044 PM 16549878 ER PT J AU Guillet, M Van der Kemp, PA Boiteux, S AF Guillet, Marie Van der Kemp, Patricia Auffret Boiteux, Serge TI dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae SO NUCLEIC ACIDS RESEARCH LA English DT Article ID URACIL-DNA-GLYCOSYLASE; BASE EXCISION-REPAIR; ESCHERICHIA-COLI; ABASIC SITES; DEOXYURIDINE TRIPHOSPHATASE; DEOXYRIBONUCLEIC-ACID; SPONTANEOUS MUTATIONS; STRAND BREAKS; IN-VIVO; YEAST AB We identified a viable allele (dut1-1) of the DUT1 gene that encodes the dUTPase activity in Saccharomyces cerevisiae. The Dut1-1 protein possesses a single amino acid substitution (Gly82Ser) in a conserved motif nearby the active site and exhibits a greatly reduced dUTPase activity. The dut1-1 single mutant exhibits growth delay and cell cycle abnormalities and shows a strong spontaneous mutator phenotype. All phenotypes of the dut1-1 mutant are suppressed by the simultaneous inactivation of the uracil DNA N-glycosylase, Ung1. However, the ung1 dut1-1 double mutant accumulates uracil in its genomic DNA. The viability of the dut1-1 mutant is greatly impaired by the simultaneous inactivation of AP endonucleases. These data strongly suggest that the phenotypes of the dut1-1 mutant result from the incorporation of dUMPs into DNA subsequently converted into AP sites. The analysis of the dut1-1 strain mutation spectrum showed that cytosines are preferentially incorporated in front of AP sites in a Rev3-dependent manner during translesion synthesis. These results point to a critical role of the Dut1 protein in the maintenance of the genetic stability. Therefore, the normal cellular metabolism, and not only its byproducts, is an important source of endogenous DNA damage and genetic instability in eukaryotic cells. C1 CEA, DSV, Dept Radiobiol & Radiopathol, UMR 217,CNRS, F-92265 Fontenay Aux Roses, France. RP Guillet, M (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM marie_guillet@dfci.harvard.edu; serge.boiteux@cea.fr NR 50 TC 38 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 7 BP 2056 EP 2066 DI 10.1093/nar/gkl139 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042IZ UT WOS:000237522900016 PM 16617146 ER PT J AU Valente, AXCN Cusick, ME AF Valente, Andre X. C. N. Cusick, Michael E. TI Yeast protein interactome topology provides framework for coordinated-functionality SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; INTERACTION NETWORKS; COMPLEX NETWORKS; BUILDING-BLOCKS; CENTRALITY; PREDICTION; ORGANIZATION; BETWEENNESS; CELL AB The architecture of the network of protein-protein physical interactions in Saccharomyces cerevisiae is exposed through the combination of two complementary theoretical network measures, betweenness centrality and 'Q-modularity'. The yeast interactome is characterized by well-defined topological modules connected via a small number of inter-module protein interactions. Should such topological inter-module connections turn out to constitute a form of functional coordination between the modules, we speculate that this coordination is occurring typically in a pairwise fashion, rather than by way of high-degree hub proteins responsible for coordinating multiple modules. The unique non-hub-centric hierarchical organization of the interactome is not reproduced by gene duplication-and-divergence stochastic growth models that disregard global selective pressures. C1 NCI, Biometry Res Grp, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Valente, AXCN (reprint author), NCI, Biometry Res Grp, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM andre@deas.harvard.edu OI X. C. N. Valente, Andre/0000-0001-6684-0596 NR 61 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 9 BP 2812 EP 2819 DI 10.1093/nar/gkl325 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700038 PM 16717286 ER PT J AU Tiffin, N Adie, E Turner, F Brunner, HG van Driel, MA Oti, M Lopez-Bigas, N Ouzounis, C Perez-Iratxeta, C Andrade-Navarro, MA Adeyemo, A Patti, ME Semple, CAM Hide, W AF Tiffin, Nicki Adie, Euan Turner, Frances Brunner, Han G. van Driel, Marc A. Oti, Martin Lopez-Bigas, Nuria Ouzounis, Christos Perez-Iratxeta, Carolina Andrade-Navarro, Miguel A. Adeyemo, Adebowale Patti, Mary Elizabeth Semple, Colin A. M. Hide, Winston TI Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes SO NUCLEIC ACIDS RESEARCH LA English DT Review ID GENOME-WIDE SEARCH; LIPOPROTEIN-LIPASE GENE; GROWTH-FACTOR-BETA; GENETICALLY ISOLATED POPULATION; HUMAN SKELETAL-MUSCLE; TUMOR-NECROSIS-FACTOR; HONG-KONG CHINESE; SUSCEPTIBILITY GENES; INSULIN-RESISTANCE; CHROMOSOME 1Q21-Q24 AB Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity. We generate and analyse a list of nine primary candidate genes for T2D genes and five for obesity. Two genes, LPL and BCKDHA, are common to these two sets. We also present a set of secondary candidates for T2D (94 genes) and for obesity (116 genes) with 58 genes in common to both diseases. C1 Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. Univ Edinburgh, Dept Med Sci, Med Genet Sect, Edinburgh, Midlothian, Scotland. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. Radboud Univ, Nijmegen Ctr Mol Life Sci, Dept Biol Mol, NL-6500 HB Nijmegen, Netherlands. Radboud Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6500 GL Nijmegen, Netherlands. Univ Pompeu Fabra, Res Unit Biomed Informat GRIB, Barcelona 08003, Spain. European Bioinformat Inst, Computat Genom Grp, EMBL Cambridge Outstn, Cambridge CB10 1SD, England. Ottawa Hlth Res Inst, Ontario Genom Innovat Ctr, Ottawa, ON K1H 8L6, Canada. Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON, Canada. Howard Univ, Natl Human Genome Ctr, Genet Epidemiol Unit, Coll Med, Washington, DC 20059 USA. Univ Ibadan, Coll Med, Ibadan, Nigeria. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Tiffin, N (reprint author), Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. EM nicki@sanbi.ac.za RI Adie, Euan/B-2805-2008; Adie, Euan/A-4825-2017; Andrade, Miguel/B-6565-2008; Semple, Colin/A-5613-2009; Hide, Winston Hide/C-7217-2009; Tiffin, Nicki/A-5914-2013; van Driel, Marc/D-5844-2013; Brunner, Han/C-9928-2013; Oti, Martin/D-9385-2015; Lopez-Bigas, Nuria/F-6193-2011; Ouzounis, Christos/G-2302-2010; Gasull, Martina/A-6630-2013 OI Adeyemo, Adebowale/0000-0002-3105-3231; Adie, Euan/0000-0001-9227-4188; Andrade, Miguel/0000-0001-6650-1711; Semple, Colin/0000-0003-1765-4118; Hide, Winston Hide/0000-0002-8621-3271; Oti, Martin/0000-0002-1005-5801; Lopez-Bigas, Nuria/0000-0003-4925-8988; FU NIDDK NIH HHS [DK060837, DK062948, R01 DK060837, R01 DK062948] NR 102 TC 88 Z9 91 U1 1 U2 7 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. PY 2006 VL 34 IS 10 BP 3067 EP 3081 DI 10.1093/nar/gkl381 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069FD UT WOS:000239430900021 PM 16757574 ER PT J AU Zhang, Y Liu, XS Liu, QR Wei, LP AF Zhang, Yong Liu, X. Shirley Liu, Qing-Rong Wei, Liping TI Genome-wide in silico identification and analysis of cis natural antisense transcripts (cis-NATs) in ten species SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; DATABASE RESOURCES; OVERLAPPING GENES; NATIONAL-CENTER; DNA-SEQUENCE; RNA; EXPRESSION; SENSE; EUKARYOTES; ANNOTATION AB We developed a fast, integrative pipeline to identify cis natural antisense transcripts (cis-NATs) at genome scale. The pipeline mapped mRNAs and ESTs in UniGene to genome sequences in GoldenPath to find overlapping transcripts and combining information from coding sequence, poly(A) signal, poly(A) tail and splicing sites to deduce transcription orientation. We identified cis-NATs in 10 eukaryotic species, including 7830 candidate sense-antisense (SA) genes in 3915 SA pairs in human. The abundance of SA genes is remarkably low in worm and does not seem to be caused by the prevalence of operons. Hundreds of SA pairs are conserved across different species, even maintaining the same overlapping patterns. The convergent SA class is prevalent in fly, worm and sea squirt, but not in human or mouse as reported previously. The percentage of SA genes among imprinted genes in human and mouse is 24-47%, a range between the two previous reports. There is significant shortage of SA genes on Chromosome X in human and mouse but not in fly or worm, supporting X-inactivation in mammals as a possible cause. SA genes are over-represented in the catalytic activities and basic metabolism functions. All candidate cis-NATs can be downloaded from http://nats.cbi.pku.edu.cn/download/. C1 Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NIDA, Mol Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Wei, LP (reprint author), Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. EM weilp@mail.cbi.pkku.edu.cn RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU NHGRI NIH HHS [R01 HG004069, R01 HG004069-01] NR 66 TC 109 Z9 110 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 12 BP 3465 EP 3475 DI 10.1093/nar/gkl473 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075TL UT WOS:000239908000013 PM 16849434 ER PT J AU Chan, AP Pertea, G Cheung, F Lee, D Zheng, L Whitelaw, C Pontaroli, AC SanMiguel, P Yuan, YN Bennetzen, J Barbazuk, WB Quackenbush, J Rabinowicz, PD AF Chan, Agnes P. Pertea, Geo Cheung, Foo Lee, Dan Zheng, Li Whitelaw, Cathy Pontaroli, Ana C. SanMiguel, Phillip Yuan, Yinan Bennetzen, Jeffrey Barbazuk, William Brad Quackenbush, John Rabinowicz, Pablo D. TI The TIGR Maize Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DIFFERENTIAL METHYLATION; GENOMIC DNA; SEQUENCES; GENES; RETROTRANSPOSONS; IDENTIFICATION; ENRICHMENT; FILTRATION; PLANTS; TOOLS AB Maize is a staple crop of the grass family and also an excellent model for plant genetics. Owing to the large size and repetitiveness of its genome, we previously investigated two approaches to accelerate gene discovery and genome analysis in maize: methylation filtration and high C(0)t selection. These techniques allow the construction of gene-enriched genomic libraries by minimizing repeat sequences due to either their methylation status or their copy number, yielding a 7-fold enrichment in genic sequences relative to a random genomic library. Approximately 900 000 gene-enriched reads from maize were generated and clustered into Assembled Zea mays (AZM) sequences. Here we report the current AZM release, which consists of similar to 298 Mb representing 243 807 sequence assemblies and singletons. In order to provide a repository of publicly available maize genomic sequences, we have created the TIGR Maize Database (http://maize.tigr.org). In this resource, we have assembled and annotated the AZMs and used available sequenced markers to anchor AZMs to maize chromosomes. We have constructed a maize repeat database and generated draft sequence assemblies of 287 maize bacterial artificial chromosome (BAC) clone sequences, which we annotated along with 172 additional publicly available BAC clones. All sequences, assemblies and annotations are available at the project website via web interfaces and FTP downloads. C1 Inst Genom Res, Rockville, MD 20850 USA. Univ Georgia, Dept Genet, Athens, GA 30602 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47906 USA. Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Rabinowicz, PD (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. EM pablo@tigr.org RI Jones, Cathy/A-7135-2011; SanMiguel, Phillip/I-2196-2015 OI Jones, Cathy/0000-0003-2844-2161; SanMiguel, Phillip/0000-0002-3742-9527 NR 23 TC 22 Z9 25 U1 0 U2 0 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 JAN 1 PY 2006 VL 34 SI SI BP D771 EP D776 DI 10.1093/nar/gkj072 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700161 PM 16381977 ER PT J AU Whelan, S de Bakker, PIW Quevillon, E Rodriguez, N Goldman, N AF Whelan, Simon de Bakker, Paul I. W. Quevillon, Emmanuel Rodriguez, Nicolas Goldman, Nick TI PANDIT: an evolution-centric database of protein and associated nucleotide domains with inferred trees SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAXIMUM-LIKELIHOOD; PHYLOGENY RECONSTRUCTION; POSITIVE SELECTION; ALGORITHM; FREQUENCIES; ALIGNMENT; MODELS AB PANDIT is a database of homologous sequence alignments accompanied by estimates of their corresponding phylogenetic trees. It provides a valuable resource to those studying phylogenetic methodology and the evolution of coding-DNA and protein sequences. Currently in version 17.0, PANDIT comprises 7738 families of homologous protein domains; for each family, DNA and corresponding amino acid sequence multiple alignments are available together with high quality phylogenetic tree estimates. Recent improvements include expanded methods for phylogenetic tree inference, assessment of alignment quality and a redesigned web interface, available at the URL http://www.ebi.ac.uk/goldman-srv/pandit. C1 EMBL European Bioinformat Inst, Hinxton CB10 1SD, Cambs, England. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Whelan, S (reprint author), EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SD, Cambs, England. EM simon@ebi.ac.uk RI Whelan, Simon/A-6638-2011; de Bakker, Paul/B-8730-2009; OI de Bakker, Paul/0000-0001-7735-7858; Rodriguez, Nicolas/0000-0002-9290-7894; Goldman, Nick/0000-0001-8486-2211 FU Wellcome Trust NR 33 TC 45 Z9 45 U1 0 U2 0 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 JAN 1 PY 2006 VL 34 SI SI BP D327 EP D331 DI 10.1093/nar/gkj087 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700071 PM 16381879 ER PT J AU Farrow, PJ Barrett, LB Stevenson, M Fisher, KD Finn, J Spice, R Allan, MA Berry, M Logan, A Seymour, LW Read, ML AF Farrow, Paul J. Barrett, Lee B. Stevenson, Mark Fisher, Kerry D. Finn, Jonathan Spice, Rachel Allan, Michael A. Berry, Martin Logan, Ann Seymour, Leonard W. Read, Martin L. TI Cytoplasmic expression systems triggered by mRNA yield increased gene expression in post-mitotic neurons SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSGENE EXPRESSION; NUCLEIC-ACIDS; PLASMID DNA; DELIVERY; THERAPY; CELLS; TRANSFECTION; EFFICIENT; PEPTIDE; AUTOGENE AB Non-viral vectors are promising vehicles for gene therapy but delivery of plasmid DNA to post-mitotic cells is challenging as nuclear entry is particularly inefficient. We have developed and evaluated a hybrid mRNA/DNA system designed to bypass the nuclear barrier to transfection and facilitate cytoplasmic gene expression. This system, based on co-delivery of mRNA(A64) encoding for T7 RNA polymerase (T7 RNAP) with a T7-driven plasmid, produced between 10- and 2200-fold higher gene expression in primary dorsal root ganglion neuronal (DRGN) cultures isolated from Sprague-Dawley rats compared to a cytomegalovirus (CMV)-driven plasmid, and 30-fold greater expression than the enhanced T7-based autogene plasmid pR011. Cell-free assays and in vitro transfections highlighted the versatility of this system with small quantities of T7 RNAP mRNA required to mediate expression at levels that were significantly greater than with the T7-driven plasmid alone or supplemented with T7 RNAP protein. We have also characterized a number of parameters, such as mRNA structure, intracellular stability and persistence of each nucleic acid component that represent important factors in determining the transfection efficiency of this hybrid expression system. The results from this study demonstrate that co-delivery of mRNA is a promising strategy to yield increased expression with plasmid DNA, and represents an important step towards improving the capability of non-viral vectors to mediate efficient gene transfer in cell types, such as in DRGN, where the nuclear membrane is a significant barrier to transfection. C1 Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Univ Birmingham, Dept Med, Mol Neurosci Grp, Birmingham B15 2TT, W Midlands, England. RP Seymour, LW (reprint author), Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England. EM Len.Seymour@clinpharm.ox.ac.uk RI Stevenson, Mark/C-3745-2009; Read, Martin/A-3505-2012; OI Read, Martin/0000-0001-8918-4333; Farrow, Paul/0000-0002-0569-9688 FU Biotechnology and Biological Sciences Research Council [BB/C515871/1] NR 37 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 11 AR e80 DI 10.1093/nar/gkl442 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075TJ UT WOS:000239907800005 PM 16835307 ER PT J AU Buerhaus, PI Donelan, K Ulrich, BT Norman, L Dittus, R AF Buerhaus, Peter I. Donelan, Karen Ulrich, Beth T. Norman, Linda Dittus, Robert TI State of the registered nurse workforce in the United States SO NURSING ECONOMICS LA English DT Article ID PERCEPTIONS; SHORTAGE; QUALITY; RNS; CAMPAIGN; STUDENTS; IMPACT; CNOS; CARE AB In the five preceding articles of this series, the authors profiled specific aspects of the nursing workforce in terms of quantitative trends as well as evolving perceptions in the eyes of nurses and nurse leaders. In this final article, the authors summarize the major findings of each piece and offer specific and actionable recommendations for nurse leaders, educators, and policymakers. While many perceptions by nurses have improved since 2002, fundamental issues still face the profession including aspects of education, supply, workplace, diversity, professional image, and quality. More importantly, two-thirds of the 185,000 nurses that have joined the workforce in recent years are age 50 or greater, so the surge in workforce supply will be short-lived if stronger efforts are not adopted and sustained. Table 2 could serve as the backbone of the strategic plan for any nurse leader highlighting the major areas for improvement and recommendations for action (see page 10). C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Sch Nursing, 221 Kirkland Hall, Nashville, TN 37240 USA. NR 20 TC 59 Z9 59 U1 0 U2 2 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JAN-FEB PY 2006 VL 24 IS 1 BP 6 EP 12 PG 7 WC Nursing SC Nursing GA 063IQ UT WOS:000239012300002 PM 16583600 ER PT J AU Lake, ET Friese, CR AF Lake, ET Friese, CR TI Variations in nursing practice environments - Relation to staffing and hospital characteristics SO NURSING RESEARCH LA English DT Article DE hospitals; nurse staffing; nursing care; organization ID JOB-SATISFACTION; MAGNET HOSPITALS; WORK INDEX; CARE; OUTCOMES; PATIENT; CLIMATE; NURSES; TURNOVER; SERVICES AB Background: While improvements in nursing practice environments are considered essential to address the nursing shortage, relatively little is known about the nursing practice environments in most hospitals. Objectives: The objectives of this study are to describe variations in nursing practice environments across hospitals and to examine their associations to hospital bed size, community size, teaching intensity, and nurse staffing levels. Methods: The research design was cross-sectional analyses of nurse survey and administrative data for 156 Pennsylvania hospitals from 1999. For comparative reference, nurse survey data from earlier years from two small samples of nursing magnet hospitals were analyzed. The nursing practice environment was measured by the Practice Environment Scale of the Nursing Work Index (PES-NWI). Results: Nursing practice environments varied greatly among the hospitals studied. The nursing practice environments of the small samples of magnet hospitals were superior to those of the Pennsylvania sample. About 17% of the hospitals in the Pennsylvania sample had favorable practice environments. Pennsylvania hospitals with better practice environments had higher RN-to-bed ratios. Practice environment differences were not associated with hospital bed size or community size. Hospitals with a modest teaching level had less favorable environments. Discussion: Considerable variation exists in the quality of hospital nursing practice environments. Five out of six hospitals are targets for improvement. Favorable nursing practice environments can be achieved in a wide variety of hospital settings. C1 Univ Penn, Dept Sociol, Sch Nursing, Secondary Fac, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA USA. RP Lake, ET (reprint author), Univ Penn, Dept Sociol, Sch Nursing, Secondary Fac, 420 Guardian Dr, Philadelphia, PA 19104 USA. EM elake@nursing.upenn.edu RI Friese, Christopher/D-2097-2013 OI Friese, Christopher/0000-0002-2281-2056 FU NINR NIH HHS [K01-NR00166, R01-NR002280, R01-NR04513, T32-NR07104] NR 54 TC 120 Z9 122 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JAN-FEB PY 2006 VL 55 IS 1 BP 1 EP 9 DI 10.1097/00006199-200601000-00001 PG 9 WC Nursing SC Nursing GA 010TU UT WOS:000235221600001 PM 16439923 ER PT J AU Silver, RJ Mehta, S Soeldner, JS Martin, BC Warram, JH Goldfine, AB AF Silver, RJ Mehta, S Soeldner, JS Martin, BC Warram, JH Goldfine, AB TI Acute insulin secretion as a predictor of weight gain in healthy humans SO OBESITY LA English DT Article DE glucose metabolism; insulin secretion; acute insulin response to glucose; insulin resistance ID HYPOTHALAMIC ARCUATE NUCLEUS; NEUROPEPTIDE-Y; LOW-CARBOHYDRATE; GLYCEMIC INDEX; BODY-WEIGHT; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; RANDOMIZED-TRIAL; SEVERE OBESITY; LOWER RATES AB Objective: We sought to determine the role of the acute insulin secretory response to glucose (AIRg) in predicting weight gain in normoglycemic persons with no family history of diabetes, who are at low risk for development of disease. Research Methods and Procedures: One hundred five individuals (64 men and 41 women) who underwent measures of weight and AIRg and insulin sensitivity index (S-I) by intravenous glucose tolerance test between 1963 and 1983 were surveyed again for weight between 1994 and 1999, with a mean follow-up of 26 4 years. Results: Mean change in weight was 8 +/- 10 kg. Annualized weight change was calculated as change in kilograms divided by change in year and averaged 0.27 +/- 0.04 kg/yr. Dividing the cohort by either median AIRg or median S-I demonstrated no association of either AIRg or S-I with total or annualized weight gain. Subgroup analysis by ideal body weight or gender did not alter the association. Furthermore, no association between AIRg and weight gain rate was seen within insulin-sensitive or -resistant subgroups, although younger age at entry was associated with greater rates of weight gain. Discussion: Our data suggest that neither AIRg nor S-I plays a role in predicting weight gain in normoglycemic individuals with no family history of diabetes. C1 Joslin Diabet Ctr, Div Clin Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Davis, Sch Med, Dept Internal Med, Sacramento, CA 95817 USA. Direct Gen Act Sociale & Sante, Geneva, Switzerland. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Div Clin Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [K23-DK02795] NR 37 TC 10 Z9 10 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD JAN PY 2006 VL 14 IS 1 BP 67 EP 72 DI 10.1038/oby.2006.9 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 055JY UT WOS:000238447800009 PM 16493124 ER PT J AU Huerta, S Li, ZP Livingston, EH AF Huerta, S Li, ZP Livingston, EH TI Outcome of portal injuries following bariatric operations SO OBESITY SURGERY LA English DT Article DE portal injuries; morbid obesity; gastric bypass; lethal complications; liver transplantation ID ROUX-EN-Y; PREOPERATIVE WEIGHT-LOSS; SEVERELY OBESE-PATIENTS; GASTRIC BYPASS; SUPER-OBESE; LIVER-TRANSPLANTATION; VEIN THROMBOSIS; UNITED-STATES; MORTALITY; MORBIDITY AB Background: Portal vein thrombosis is rare following Roux-en-Y gastric bypass (RYGBP). Its natural history is dependent on the etiology of the thrombosis. Iatrogenic injuries at bariatric operations resulting in portal vein thrombosis are lethal complications typically necessitating a liver transplant, whereas postoperative portal vein thrombosis without an injury to the portal vein has a benign course. There are currently no data on management or prognostic factors of portal vein thrombosis after bariatric operations. Methods: 3 patients referred for liver transplantation secondary to portal vein injury following bariatric surgery between 2000 and 2003 are presented. Results: 2 super-obese (BMI >= 50 kg/M2) and 1 morbidly obese (BMI 44 kg/M2) patients sustained portal vein injuries during bariatric surgery (RYGBP 2, VBG 1) by experienced bariatric surgeons. In each case, the portal injury was identified and repaired. Thrombosis followed reconstruction in all 3 patients. All 3 underwent emergency liver transplantation, but died of sepsis and multi-organ failure following transplantation. Review of the literature found no cases of traumatic portal vein injuries following bariatric operations and 2 cases of postoperative portal vein thrombosis: 1 following LRYGBP (BMI 46) and one after a Lap-Band (BMI 41). Conclusion: Injury to the portal vein resulting from difficulty in discerning the anatomy of the intra-abdominal structures in the morbidly obese, is a lethal complication of bariatric surgery. Super-obese patients submitting to bariatic surgery should lose weight, undergo a two-stage bariatric procedure, or undergo laparoscopic RYGBP to minimize the risk of portal injury. Postoperative portal vein thrombosis has a benign course and can be managed conservatively. C1 Univ Texas, SW Med Ctr, VA N Texas Hlth Care Syst, Dallas, TX 75230 USA. VA Greater Los Angeles Syst, Los Angeles, CA USA. RP Huerta, S (reprint author), 4500 Lancaster Rd, Dallas, TX 75216 USA. EM Sergio.Huerta@UTSouthwestern.edu NR 28 TC 9 Z9 9 U1 0 U2 2 PU F D-COMMUNICATIONS INC PI TORONTO PA 3100 BAYVIEW AVE, UNIT 4, TORONTO, ONTARIO M2N 5L3, CANADA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD JAN PY 2006 VL 16 IS 1 BP 105 EP 109 DI 10.1381/096089206775222203 PG 5 WC Surgery SC Surgery GA 006WG UT WOS:000234927800021 PM 16417768 ER PT J AU Browning, MF Levy, HL Wilkins-Haug, LE Larson, C Shih, VE AF Browning, MF Levy, HL Wilkins-Haug, LE Larson, C Shih, VE TI Fetal fatty acid oxidation defects and maternal liver disease in pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2004) CY MAR 07-10, 2004 CL Orlando, FL SP Soc Inherited Metabolic Disorders ID 3-HYDROXYACYL-COA DEHYDROGENASE-DEFICIENCY; LOW PLATELETS SYNDROME; HELLP-SYNDROME; INBORN-ERRORS; DIAGNOSIS; HEMOLYSIS; ENZYMES; MANAGEMENT; DISORDERS; COMPLICATIONS AB OBJECTIVE: The objective was to evaluate the relationships between all types of fetal fatty acid oxidation defects and maternal liver disease, including acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. METHODS: This was a case-control study comparing fetal fatty acid oxidation defects to the outcome of maternal liver disease. Fifty case infants with fatty acid oxidation defects were identified, with 25 matched controls collected per case. This generated a total of 50 case infants and 1,250 control infants. Pregnancies were evaluated for the presence of maternal liver disease (comprised of acute fatty liver of pregnancy, HELLP syndrome, and preeclampsia evolving into HELLP syndrome) using a conditional logistic regression model. Subgroup analysis compared long chain to short and medium chain fatty acid defects. RESULTS: Maternal liver disease was noted in 16.00% of all fatty acid oxidation defect pregnancies compared with 0.88% in the general population (odds ratio 20.4, 95% confidence interval 7.82-53.2). These pregnancies demonstrated an 18.1-fold increase in maternal liver disease when compared with our matched population controls with unaffected fetuses. All classifications of fatty acid oxidation defects were at high risk of developing maternal liver disease. Long chain defects were 50 times more likely than controls to develop maternal liver disease and short and medium chain defects were 12 times more likely to develop maternal liver disease. CONCLUSION: Maternal liver disease is significantly higher across the entire spectrum of fatty acid oxidation defects pregnancies compared with the matched control population. Notably, there is significant risk to the pregnancies with fetuses affected with short and medium chain defects, not just those with fetal long chain fatty acid oxidation defects as previously reported. Future studies should examine the pathophysiology of all infant fatty acid oxidation defects and its implications for maternal liver disease for improved future health outcomes. C1 Harvard Univ, Ctr Human Genet, Simches Res Ctr,Brigham & Womens Hosp, Massachusetts Gen Hosp,Sch Med,Childrens Hosp Bos, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, New England Newborn Screening Program, Boston, MA 02125 USA. RP Browning, MF (reprint author), Harvard Univ, Ctr Human Genet, Simches Res Ctr,Brigham & Womens Hosp, Massachusetts Gen Hosp,Sch Med,Childrens Hosp Bos, Room 2222,185 Cambridge St, Boston, MA 02114 USA. EM mfbrowning@partners.org NR 31 TC 37 Z9 42 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2006 VL 107 IS 1 BP 115 EP 120 DI 10.1097/01.AOG.0000191297.47183.bd PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997ZN UT WOS:000234287700018 PM 16394048 ER PT J AU Mesholam-Gately, R Seidman, LJ AF Mesholam-Gately, Raquelle Seidman, Larry J. BE Brewer, WJ Castle, D Pantelis, C TI Genetics and family influences on olfaction: a focus in schizophrenia SO OLFACTION AND THE BRAIN LA English DT Article; Book Chapter ID NEUROPSYCHOLOGICAL RISK INDICATORS; SCHIZOTYPAL PERSONALITY-DISORDER; EYE-MOVEMENT DYSFUNCTION; CARD SORTING PERFORMANCE; EVENT-RELATED POTENTIALS; VERBAL WORKING-MEMORY; PD TEST BATTERY; NONPSYCHOTIC RELATIVES; 1ST-DEGREE RELATIVES; TEMPORAL-LOBE C1 [Mesholam-Gately, Raquelle] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Med Sch,Publ Psychiat Div,Dept Psychiat, Jamaica Plain, MA 02130 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Commonwealth Res Ct, Med Sch,Publ Psychiat Div,Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mesholam-Gately, R (reprint author), Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Med Sch,Publ Psychiat Div,Dept Psychiat, Lemuel Shattuck Hosp Campus,180 Morton St, Jamaica Plain, MA 02130 USA. RI Pantelis, Christos/H-7722-2014 OI Pantelis, Christos/0000-0002-9565-0238 NR 84 TC 1 Z9 1 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-84922-7 PY 2006 BP 167 EP 182 DI 10.1017/CBO9780511543623.011 D2 10.1017/CBO9780511543623 PG 16 WC Psychology, Biological; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA BXL58 UT WOS:000296293500011 ER PT J AU Kornblum, N Ayyanar, K Benimetskaya, L Richardson, P Iacobelli, M Stein, CA AF Kornblum, N Ayyanar, K Benimetskaya, L Richardson, P Iacobelli, M Stein, CA TI Defibrotide, a polydisperse mixture of single-stranded phosphodiester oligonucleotides with lifesaving activity in severe hepatic veno-occlusive disease: Clinical outcomes and potential mechanisms of action SO OLIGONUCLEOTIDES LA English DT Review ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; HIGH-RISK POPULATION; PLASMINOGEN-ACTIVATOR; SIGNIFICANT TOXICITY; COMPASSIONATE-USE; LIVER; DIAGNOSIS; FAILURE AB Veno-occlusive disease of the liver (VOD) remains a troubling and potentially fatal complication of high-dose chemotherapy and hematopoietic stem cell transplantation conditioning regimens. No effective therapy has been available for these patients to date, and the best supportive care measures remain woefully inadequate. Defibrotide (DF) (Gentium, S.p.A., Como, Italy), a polydisperse mixture of all the single-stranded phosphodiester oligodeoxyribonucleotides that can be obtained from the controlled depolymerization of porcine intestinal mucosal genomic DNA, seems to offer a safe and effective treatment for some patients suffering from severe VOD, a condition for which no accepted standard therapy currently exists. Early clinical studies evaluating the efficacy of DF for the treatment of severe VOD in patients undergoing hematopoietic stem cell transplantation have been very encouraging. Approximately 45% of the patients treated in multiple initial phase 11 clinical trials achieved a complete response at day +100, demonstrating normalization of serum bilirubin and resolution of the clinical syndrome. However, although multi-institutional, these represented single arm studies. A large, FDA-approved, pivotal, prospective, multi-institutional, global phase III trial of DF vs. historical controls (best available therapy) commenced in the first quarter of 2006 and should provide further validation of DF's efficacy. The drug seems to have few significant side effects, and almost all test subjects who have received this treatment have tolerated it well. Although the mechanism of action remains unclear, the drug exerts minimal systemic anticoagulant effects yet appears to induce numerous antithrombotic and profibrinolytic effects both in vitro and in vivo. It may function as an adenosine receptor agonist and causes increased concentrations of endogenous prostaglandins, which modulate thrombomodulin, platelets, and fibrinolysis. It also appears to block lipopolysaccharide (LPS)-induced tissue factor (TF) expression. However, despite the fact the DF is composed of oligonucleotides, its mechanism of action, which at the present time is unclear, is not related to Watson-Crick base pair-dependent downregulation of gene expression but is rather likely a result of its polyanionic nature. C1 Albert Einstein Montefiore Canc Ctr, Montefiore Med Ctr, Bronx, NY 10467 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Gentium SpA, I-22079 Villa Guardia, Italy. RP Stein, CA (reprint author), Albert Einstein Montefiore Canc Ctr, Montefiore Med Ctr, 111 E 210 St, Bronx, NY 10467 USA. EM cstein@montefiore.org NR 40 TC 20 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-4576 J9 OLIGONUCLEOTIDES JI Oligonucleotides PY 2006 VL 16 IS 1 BP 105 EP 114 DI 10.1089/oli.2006.16.105 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 030DU UT WOS:000236614800009 PM 16584299 ER PT J AU Michalski, MJ Vanderwerker, LC Prigerson, HG AF Michalski, Marion J. Vanderwerker, Lauren C. Prigerson, Holly G. TI Assessing grief and bereavement: Observations from the field SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID COMPLICATED GRIEF; HEALTH; COMMUNITY; ADULTS; SCALE; DEPRESSION; EXPERIENCE; DISABILITY AB The purpose of this article is to describe the evaluations involved in the Yale Bereavement Study (YBS), a three-year NIMH and NCI-funded longitudinal study conducted from January 2000 through May 2003. The quantitative and qualitative questions included in the YBS gave the respondents an opportunity to describe their most recent loss, rate and review their past losses, and assess all aspects of their current life situations. In this article, the first author describes, in a qualitative manner, the ways in which this assessment, per se, appeared helpful and not harmful to the respondents. Also, developed here is the implication for potential application of a modified version of the YBS which could be used in both research and clinical practice. C1 Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Michalski, MJ (reprint author), 616 Spring St, Southington, CT 06489 USA. FU NCI NIH HHS [CA106370, R01 CA106370]; NIMH NIH HHS [MH56529, MH63892] NR 36 TC 4 Z9 4 U1 4 U2 7 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2006 VL 54 IS 2 BP 91 EP 106 PG 16 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 164HB UT WOS:000246223200001 PM 17876964 ER PT J AU Ren, J Bharti, A Raina, D Chen, W Ahmad, R Kufe, D AF Ren, J Bharti, A Raina, D Chen, W Ahmad, R Kufe, D TI MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90 SO ONCOGENE LA English DT Article DE MUC1; heregulin; c-Src; HSP70; HSP90; mitochondria ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; BETA-CATENIN; BREAST-CARCINOMA; MONOCLONAL-ANTIBODY; GENE-TRANSCRIPTION; CYTOPLASMIC TAIL; TYROSINE KINASE; PROTEIN IMPORT; MAMMARY-GLAND AB The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by most human carcinomas. The MUC1 C-terminal subunit localizes to mitochondria and blocks stress-induced activation of the intrinsic apoptotic pathway. How MUC1 is delivered to mitochondria is not known. The present studies demonstrate that MUC1 forms intracellular complexes with HSP70 and HSP90. We show that the MUC1 cytoplasmic domain binds directly to HSP70 in vitro. By contrast, binding of MUC1 to HSP90 in vitro is induced by c-Src-mediated phosphorylation of the MUC1 cytoplasmic domain. c-Src also increases binding of MUC1 to HSP90 in cells. In concert with these results, we show that heregulin (HRG), a ligand for ErbB receptors, activates c-Src and, in turn, stimulates binding of MUC1 to HSP90. We also show that inhibitors of c-Src or HSP90 block HRG-induced targeting of MUC1 to mitochondria and integration of MUC1 into the mitochondrial outer membrane. These findings indicate that MUC1 is delivered to mitochondria by a mechanism involving activation of the ErbB receptor-c-Src pathway and transport by the molecular chaperone HSP70/HSP90 complex. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098] NR 43 TC 85 Z9 85 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 1 BP 20 EP 31 DI 10.1038/sj.onc.1209012 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 999QX UT WOS:000234406400003 PM 16158055 ER PT J AU Ota, H Tokunaga, E Chang, K Hikasa, M Iijima, K Eto, M Kozaki, K Akishita, M Ouchi, Y Kaneki, M AF Ota, H Tokunaga, E Chang, K Hikasa, M Iijima, K Eto, M Kozaki, K Akishita, M Ouchi, Y Kaneki, M TI Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells SO ONCOGENE LA English DT Article DE Sirt1; sirtinol; cellular senescence; Ras; MAPK; Akt/PKB ID HISTONE DEACETYLASE INHIBITORS; TERMINAL PROLIFERATION ARREST; CELLULAR SENESCENCE; TUMOR-CELLS; HUMAN-FIBROBLASTS; IN-VIVO; DEPSIPEPTIDE FR901228; TRANSCRIPTION FACTORS; PROTEIN DEACETYLASES; PC12 CELLS AB The induction of senescence-like growth arrest has emerged as a putative contributor to the anticancer effects of chemotherapeutic agents. Clinical trials are underway to evaluate the efficacy of inhibitors for class I and II histone deacetylases to treat malignancies. However, a potential antiproliferative effect of inhibitor for Sirt1, which is an NAD(+)-dependent deacetylase and belongs to class III histone deacetylases, has not yet been explored. Here, we show that Sirt1 inhibitor, Sirtinol, induced senescence-like growth arrest characterized by induction of senescence-associated beta-galactosidase activity and increased expression of plasminogen activator inhibitor 1 in human breast cancer MCF-7 cells and lung cancer H1299 cells. Sirtinol-induced senescence-like growth arrest was accompanied by impaired activation of mitogen-activated protein kinase ( MAPK) pathways, namely, extracellular-regulated protein kinase, c-jun N-terminal kinase and p38 MAPK, in response to epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). Active Ras was reduced in Sirtinol-treated senescent cells compared with untreated cells. However, tyrosine phosphorylation of the receptors for EGF and IGF-I and Akt/PKB activation were unaltered by Sirtinol treatment. These results suggest that inhibitors for Sirt1 may have anticancer potential, and that impaired activation of Ras-MAPK pathway might take part in a senescence-like growth arrest program induced by Sirtinol. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Tokyo, Japan. Shriners Hosp Children, Boston, MA USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@partners.org FU NIDDK NIH HHS [R01DK058127] NR 67 TC 251 Z9 268 U1 1 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 2 BP 176 EP 185 DI 10.1038/sj.onc.1209049 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 002AK UT WOS:000234583600002 PM 16170353 ER PT J AU Ryan, DP AF Ryan, David P. TI Nonsurgical approaches to colorectal cancer SO ONCOLOGIST LA English DT Article DE nonsurgical; radiofrequency ablation; chemoembolization; radiation ID RADIOFREQUENCY ABLATION; RADIATION-THERAPY; LIVER METASTASES; CHEMOTHERAPY; TRIAL; SIR-SPHERES(R); FLUOROURACIL; LEUCOVORIN; IRINOTECAN; CARCINOMA AB It is time to challenge the current orthodoxy that frowns upon surgical and nonsurgical methods of tumor reduction for patients with metastatic colon cancer. Although the studies conducted with radiofrequency ablation, chemoembolization, and radiation therapy in patients with metastatic colon cancer have tended to be small and may have been subject to selection bias, they have produced survival data that require careful consideration. At the very least, it is clear that locoregional approaches to debulking tumors are feasible and that their combination with systemic chemotherapy should be investigated. C1 Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Gastrointestinal Canc Ctr, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Gastrointestinal Canc Ctr, Boston, MA 02114 USA. EM dpryan@partners.org NR 16 TC 3 Z9 3 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2006 VL 11 IS 9 BP 999 EP 1002 DI 10.1634/theoncologist.11-9-999 PG 4 WC Oncology SC Oncology GA 095RR UT WOS:000241326100009 PM 17030641 ER PT J AU Moy, B Goss, PE AF Moy, Beverly Goss, Paul E. TI Lapatinib: Current status and future directions in breast cancer SO ONCOLOGIST LA English DT Article DE lapatinib; GW572016; dual tyrosine kinase inhibitor; breast cancer; EGFR; ErbB-1; ErbB-2; HER-2 ID GROWTH-FACTOR RECEPTOR; TYROSINE-KINASE-INHIBITOR; ENDOCRINE-THERAPY; ADJUVANT CHEMOTHERAPY; SIGNALING NETWORK; PROGNOSTIC VALUE; CLINICAL-TRIALS; EGFR FAMILY; IN-VITRO; GW572016 AB Lapatinib is an oral receptor tyrosine kinase inhibitor, targeting both the ErbB-1 and ErbB-2 receptors. Preclinical in vitro and in vivo models indicate that lapatinib is active as monotherapy, synergistically in combination with trastuzumab, and in trastuzumab-resistant cell lines. Early clinical trials also provide evidence in patients that lapatinib is active against breast cancer. This paper reviews results of phase II and III clinical trials of lapatinib in metastatic breast cancer, evidence for its potential in patients with brain metastases, and current clinical trials as adjuvant treatment in early-stage disease. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes is allowing us to bring patient-specific novel therapies such as lapatinib to the clinic. C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 90 TC 92 Z9 105 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2006 VL 11 IS 10 BP 1047 EP 1057 DI 10.1634/theoncologist.11-10-1047 PG 11 WC Oncology SC Oncology GA 108JI UT WOS:000242235700001 PM 17110623 ER PT J AU Astrakas, L Ye, S Zarifi, M Makedon, F Tzika, AA AF Astrakas, L Ye, S Zarifi, M Makedon, F Tzika, AA TI The clinical perspective of large scale projects: A case study of multiparametric MR imaging of pediatric brain tumors SO ONCOLOGY REPORTS LA English DT Article DE magnetic resonance; pediatric tumors; data sharing; medical databases; data mining ID SPECTROSCOPY AB Current developments in medical information technologies provide the clinical researcher with overwhelming amounts of data that need to be retrieved, organized, analyzed, and shared using secure, efficient, and robust protocols. The development of a local research database can provide an infrastructure for improved data management and detailed data analysis. For example, a pediatric brain tumor database of magnetic resonance imaging data, including conventional MRI imaging, hemodynamic MRI, diffusion weighted MRI and MR spectroscopic imaging, combined with neuropathological and neurological evaluation data, will significantly enhance the assessment and treatment of pediatric brain tumor patients. Furthermore, a negotiation system by which different clinical research facilities can share and combine data will permit re-analyses and meta-analyses of large data arrays that are beyond the focus or time constraints of the original researchers. Such a system will greatly enhance the utility of different data sets to a wide array of scientists. At present, efforts to organize medical data locally and between different sites is limited by diversity, interoperability, security, and accountability difficulties. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. Dartmouth Coll, Hanover, NH 03755 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 NR 17 TC 3 Z9 3 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PY 2006 VL 15 SI SI BP 1065 EP 1069 PG 5 WC Oncology SC Oncology GA 022OS UT WOS:000236066000017 PM 16525702 ER PT J AU Marasco, WA AF Marasco, WA TI A strategy for global collaborations to develop human monoclonal antibody (mAb) drugs for the treatment of cancer SO ONCOLOGY RESEARCH LA English DT Meeting Abstract CT BioFunding Summit on Anti-Cancer Innovations and Global Collaborations CY OCT 13, 2005 CL Peking Union Med Coll, Beijing, PEOPLES R CHINA SP Inst Medicinal Biotechnol, Asian Fund Canc Res, PriceWaterhouseCoopers, YM BioSciences, Novartis, Cybrdi, Int Genom Consortium, Nextech Venture, ViVo Ventures, Hogan & Hartson, Law Firm HO Peking Union Med Coll C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 2006 VL 15 IS 10-12 BP 458 EP 458 PG 1 WC Oncology SC Oncology GA 030GT UT WOS:000236623200011 ER PT J AU Slakter, JS Bochow, T D'Amico, DJ Marks, B Jerdan, J Sullivan, EK AF Slakter, JS Bochow, T D'Amico, DJ Marks, B Jerdan, J Sullivan, EK CA Anecortave Acetate Clin Study Grp TI Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Macula-Society CY JUL 15, 2005 CL Key Biscayne, FL ID STEROIDS AB Purpose: To compare 1-year safety and efficacy of anecortave acetate 15 mg with photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT treatment. Design: Prospective, masked, randomized, multicenter, parallel group, active control, noninferiority clinical trial. Participants: Five hundred thirty patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration were randomized to treatment with either anecortave acetate 15 mg or PDT. Methods: In the anecortave acetate group, the drug was administered under the Tenon's capsule as a periocular posterior juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the first administration of anecortave acetate, patients in this treatment group received a sham PDT treatment, and sham PDT treatments were repeated every 3 months if there was evidence of leakage on fluorescein angiography (FA). Patients assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed based upon FA, and a sham PJD procedure at the beginning of the study and at month 6. Best-corrected visual acuity was determined at baseline and all follow-up visits. Safety data were regularly reviewed by an independent safety committee. Main Outcome Measure: Percent responders (patients losing < 3 lines of vision) at month 12. Results: Percent responders in the anecortave acetate and PDT groups were 45% and 49%, respectively (not statistically different, P = 0.43). The confidence interval (CI) for the difference ranged from -13.2% favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome for anecortave acetate was improved in patients for whom reflux was controlled and who were treated within the 6-month treatment window (57% vs. 49%; 95% Cl, -4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse events related to the study drug were reported in either treatment group. Conclusions: The safety and efficacy outcomes in this study demonstrate that the benefits of anecortave acetate for the treatment of choroidal neovascularization outweigh the risks associated with either the drug or the PJD administration procedure. C1 Vitreous Retina Macula Consultants New York, New York, NY USA. Eye Care Associates E Texas, Tyler, TX USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Alcon Res Ltd, Ft Worth, TX USA. RP Slakter, JS (reprint author), 460 Pk Ave,5th Floor, New York, NY 10022 USA. NR 19 TC 65 Z9 72 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 JAN PY 2006 VL 113 IS 1 BP 3 EP 13 DI 10.1016/j.ophtha.2005.10.019 PG 11 WC Ophthalmology SC Ophthalmology GA 998JJ UT WOS:000234314400002 PM 16368146 ER PT S AU Chang, SK Errabelli, D Rizvi, I Solban, N O'Riordan, K Hasan, T AF Chang, Sung K. Errabelli, Divya Rizvi, Imran Solban, Nicolas O'Riordan, Katherine Hasan, Tayyaba BE Achilefu, SI Bornhop, DJ Raghavachari, R TI Molecular imaging of photodynamic therapy - art. no. 609701 SO Optical Molecular Probes for Biomedical Applications SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Molecular Probes for Biomedical Applications CY JAN 22-24, 2006 CL San Jose, CA DE photodynamic therapy; optical imaging; molecular imaging ID ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER; VASCULAR DAMAGE; RADIATION; TUMORS; MICE; ANTIBODY AB Recent advances in light sources, detectors and other optical imaging technologies coupled with the development of novel optical contrast agents have enabled real-time, high resolution, in vivo monitoring of molecular targets. Noninvasive monitoring of molecular targets is particularly relevant to photodynamic therapy (PDT), including the delivery of photosensitizer in the treatment site and monitoring of molecular and physiological changes following treatment. Our lab has developed optical imaging technologies to investigate these various aspects of photodynamic therapy (PDT). We used a laser scanning confocal microscope to monitor the pharmacokinetics of various photosensitizers in in vitro as well as ex vivo samples, and developed an intravital fluorescence microscope to monitor photosensitizer delivery in vivo in small animals. A molecular specific contrast agent that targets the vascular endothelial growth factor (VEGF) was developed to monitor the changes in the protein expression following PDT. We were then able to study the physiological changes due to post-treatment VEGF upregulation by quantifying vascular permeability with in vivo imaging. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chang, SK (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6139-3 J9 P SOC PHOTO-OPT INS PY 2006 VL 6097 BP 9701 EP 9701 AR 609701 DI 10.1117/12.649844 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BEF90 UT WOS:000237160900001 ER PT J AU Friedlander, AH Golub, MS AF Friedlander, AH Golub, MS TI The significance of carotid artery atheromas on panoramic radiographs in the diagnosis of occult metabolic syndrome SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; SUBCLINICAL ATHEROSCLEROSIS; ASSOCIATION CONFERENCE; DIABETES-MELLITUS; CHOLESTEROL; PREVALENCE AB Objective. Metabolic syndrome (MetS), the co-occurrence of abdominal obesity, hypertriglyceridemia, reduced HDL cholesterol, hypertension, and insulin resistance promotes carotid atherosclerosis and stroke. The objective of this study was to determine if the presence of calcified atheromas detected on panoramic radiographs of individuals free of overt vascular disease may herald occult MetS. Study design. Ninety-four individuals (mean age 65.6 years) with a calcified atheroma detected by a VA dental clinic were evaluated. A like-aged group was used for comparative analysis. Results. Fifteen percent of individuals (mean age 64 years) with an atheroma had occult MetS. Mean waist circumference was 116 cm, BMI 32.7 kg/m(2), triglycerides 250 mg/dL, HDL cholesterol 35 mg/dL, blood pressure 147/87 mm Hg, and glucose 117 mg/dL. Only 6% of controls had occult MetS but this difference in prevalence was not proven to be statistically significant (P = .059). Conclusion. Some individuals with a calcified atheroma may have undiagnosed MetS and should be referred to their physician because aggressive management may preclude a stroke. C1 VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Grad Med Educ, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 40 TC 14 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2006 VL 101 IS 1 BP 95 EP 101 DI 10.1016/j.tripleo.2005.04.027 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 997ZP UT WOS:000234287900015 PM 16360613 ER PT J AU Querol, M Chen, JW Bogdanov, AA AF Querol, M Chen, JW Bogdanov, AA TI A paramagnetic contrast agent with myeloperoxidase-sensing properties SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID DESORPTION/IONIZATION MASS-SPECTROMETRY; LOW-DENSITY-LIPOPROTEIN; HYPOCHLOROUS ACID; ENZYMATIC OLIGOMERIZATION; REDOX PROPERTIES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CROSS-LINKING; LACTOPEROXIDASE; MRI AB Myeloperoxidase (MPO) is an essential component of inflammatory response in norm and pathology. With an ultimate goal of non-invasive imaging of MPO we used a gadolinium-chelating bis(5-hydroxytrytamide) derivative of diethylenetetraamine pentaacetic acid (L-1 - Gd3+ salt) as a paramagnetic sensor of enzymatic activity. We tested whether L-1 - Gd3+ is active in reducing the oxidized form of myeloperoxidase, generated as a result of hydrogen peroxide reduction by the enzyme. We expected that upon activation by MPO/H2O2 L-1 - Gd3+ would not only oligomerise but also bind to other macromolecules present in the media and that the overall process will give rise to a net T-1-weighted MRI signal increase. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, S2-804,55 Lake Ave, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu NR 62 TC 37 Z9 38 U1 1 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2006 VL 4 IS 10 BP 1887 EP 1895 DI 10.1039/b601540a PG 9 WC Chemistry, Organic SC Chemistry GA 041NH UT WOS:000237462400009 PM 16688334 ER PT J AU Xu, B Pelish, H Kirchhausen, T Hammond, GB AF Xu, Bo Pelish, Henry Kirchhausen, Tomas Hammond, Gerald B. TI Large scale synthesis of the Cdc42 inhibitor secramine A and its inhibition of cell spreading SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID DIVERSITY-ORIENTED SYNTHESIS; PRODUCT-LIKE LIBRARIES; NATURAL PRODUCT; CHEMICAL GENETICS; BIOLOGY; RHO; MOLECULES; CHEMISTRY; GTPASES; RAC AB We describe a large scale synthesis of secramine A. Consistent with its ability to inhibit activation of the small GTPase Cdc42, we find that secramine A inhibits cell spreading, a process previously shown to be Cdc42-dependent. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Hammond, GB (reprint author), Univ Louisville, Dept Chem, Louisville, KY 40292 USA. RI Xu, Bo/C-2594-2008 FU NIGMS NIH HHS [GM 62566] NR 18 TC 20 Z9 20 U1 1 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2006 VL 4 IS 22 BP 4149 EP 4157 DI 10.1039/b609143a PG 9 WC Chemistry, Organic SC Chemistry GA 101EA UT WOS:000241720500018 PM 17312971 ER PT J AU Levine, RA AF Levine, RA TI Typewriter tinnitus: A carbamazepine-responsive syndrome related to auditory nerve vascular compression SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE paroxysmal; pharmacology; microvascular; treatment ID 8TH CRANIAL NERVE; CEREBELLOPONTINE ANGLE; PAROXYSMAL TINNITUS; FACIAL SPASM AB Six subjects with similar unilateral tinnitus that was fully suppressed by carbamazepine have been identified. Their ages at the time of the sudden onset of their tinnitus ranged from 39 to 87 years ( mean 67). The 3 men had right ear tinnitus. Two of the 3 women had left ear tinnitus. All 6 described a staccato quality of their intermittent tinnitus ('like a typewriter in the background, pop corn, Morse code'). Five of the 6 subjects had no other hearing or vestibular complaints; their audiograms were symmetric and consistent with their ages. Vascular compression of the auditory nerve ipsilateral to the tinnitus was detected in 4 of the 5 subjects imaged. The similarities between typewriter tinnitus and other cranial nerve syndromes associated with vascular compression ( trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia) suggest that surgical decompression of the auditory nerve can relieve medication-refractive cases of typewriter tinnitus. Copyright (C) 2006 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM ObbyLevine@yahoo.com NR 13 TC 39 Z9 43 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2006 VL 68 IS 1 BP 43 EP 46 DI 10.1159/000090490 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 018OY UT WOS:000235775900012 PM 16514262 ER PT J AU Seshamani, M Ruiz, C Schwartz, SK Mirza, N AF Seshamani, M Ruiz, C Schwartz, SK Mirza, N TI Cymetra (TM) injections to treat leakage around a tracheoesophageal puncture SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the Triological-Society CY JAN, 2005 CL Washington, DC SP Triol Soc, Eastern Sect DE voice prosthesis; tracheoesophageal puncture; laryngectomy; leakage; Cymetra ID VOICE; REHABILITATION; RESTORATION AB Tracheoesophageal puncture (TEP) is a commonly used method of voice restoration following total laryngectomy, but leakage around the prosthesis is prevalent. Several treatments for leakage have been proposed in the literature, but with varying success. This paper examines the efficacy of Cymetra (TM) to help shrink the TEP site and stop leakage. Six patients with leaking TEP sites refractory to downsizing and/or cautery were selected for the study. Injection sites were determined based on the primary sites of leakage. Cymetra was rehydrated with 1.0% lidocaine saline solution and injected via a 23-gauge needle a few millimeters deep to the mucosa, approximately 2 mm from the edge. The patients were followed for up to 13 months. Following 1 trial of Cymetra injection, 4 patients achieved successful results. Only 1 patient has not yet achieved full resolution of leakage. Cymetra may provide a safer and more effective option for resolution of leakage than other methods currently employed. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Seshamani, M (reprint author), Univ Penn, Sch Med, Box 265,3450 Hamilton Walk, Philadelphia, PA 19104 USA. EM meena.seshamani@marshallscholarship.org NR 6 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2006 VL 68 IS 3 BP 146 EP 148 DI 10.1159/000091277 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 015VX UT WOS:000235580500005 PM 16449823 ER PT J AU Hosalkar, HS Fox, EJ Delaney, T Torbert, JT Ogilvie, CM Lackman, RD AF Hosalkar, HS Fox, EJ Delaney, T Torbert, JT Ogilvie, CM Lackman, RD TI Desmoid tumors and current status of management SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; AGGRESSIVE FIBROMATOSIS; RADIATION-THERAPY; RADIOTHERAPY; MUTATIONS; TRISOMY-8; PATTERNS; SURGERY; GENE AB Desmoid tumors, also known as aggressive fibromatosis, are rare fibroblastic tumors that exhibit a wide range of local aggressiveness, from largely indolent to locally destructive. Understanding of the pathogenesis and the great heterogeneity in the natural history of desmoid tumors is invaluable to the development of therapeutic strategies. The optimal treatment protocol has not yet been established and, in many cases, a multidisciplinary approach including surgery, chemotherapy, and radiation therapy has been employed. The rarity of cases in even major tumor centers has traditionally limited the ability to study this disease. Several novel pharmacologic and biologic treatment approaches are actively being developed, although long-term follow-up is needed for their substantiation. C1 Univ Penn, Dept Orthoped Oncol, Philadelphia, PA 19106 USA. Massachusetts Gen Hosp, Dept Med Oncol, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Fox, EJ (reprint author), Univ Penn, Dept Orthoped Oncol, 301 S 8th St,Garfield Duncan Bldg, Philadelphia, PA 19106 USA. EM edward.fox@uphs.upenn.edu NR 51 TC 27 Z9 28 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JAN PY 2006 VL 37 IS 1 BP 53 EP + DI 10.1016/j.ocl.2005.08.004 PG 12 WC Orthopedics SC Orthopedics GA 994WF UT WOS:000234061200007 PM 16311111 ER PT J AU Vaughan, N James, T McDermott, D Griest, T Fausti, S AF Vaughan, N James, T McDermott, D Griest, T Fausti, S TI A 5-year prospective study of diabetes and hearing loss in a veteran population SO OTOLOGY & NEUROTOLOGY LA English DT Article DE diabetes; hearing loss; hemoglobin A1c; insulin; pure-tone threshold ID INNER-EAR; MELLITUS; MICROANGIOPATHY; AGE AB Hypothesis: Veterans with diabetes will have significantly greater hearing loss than nondiabetic veterans. Background: The association between diabetes and hearing loss remains unclear despite the volume of research that has been devoted to the question. Often, differences in hearing thresholds between diabetic and nondiabetic patients are confounded by age and noise exposure. Methods: In this 5-year prospective study, 342 diabetic veterans and 352 nondiabetic veterans from the Portland VA Medical Center in Oregon were tested on a variety of audiometric measures, including pure-tone thresholds. Results: Age and noise exposure were accounted for in the analyses. There was a trend toward greater hearing loss in diabetic patients 60 years of age and younger across the frequency range. These differences were statistically significant only in the highest frequencies tested (10, 12.5, 14, and 16 kHz). The effects of both diabetes and noise exposure on high-frequency hearing thresholds were dependent on age. For patients older than 60 years, the mean thresholds were not significantly different. Conclusion: These results suggest that diabetic patients 60 years old or younger may show early high-frequency hearing loss similar to early presbycusis. After age 60, difference in hearing loss between diabetic and nondiabetic patients was reduced. C1 Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Vaughan, N (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Nancy.Vaughan@med.va.gov NR 14 TC 37 Z9 42 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2006 VL 27 IS 1 BP 37 EP 43 DI 10.1097/01.mao.0000194812.69556.74 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 004AO UT WOS:000234724600008 PM 16371845 ER PT J AU Handzel, O Burgess, BJ Nadol, JB AF Handzel, O Burgess, BJ Nadol, JB TI Histopathology of the peripheral vestibular system after cochlear implantation in the human SO OTOLOGY & NEUROTOLOGY LA English DT Article DE histopathology; cochlear implantation; peripheral vestibular system; Scarpa's ganglion cells; temporal bones ID ENDOLYMPHATIC HYDROPS; SCARPAS GANGLION; OBLITERATION; OTOPATHOLOGY; VERTIGO AB Objectives: The objective of this study was to describe the histology of the peripheral vestibular system in temporal bones from patients who in life had undergone cochlear implantation and to correlate the findings with previous reports of vestibular dysfunction after cochlear implantation. This is the first quantitative report of the impact of implantation on the vestibular neuronal end organ. Methods: There were 19 temporal bones available for histologic study. Of these, 17 were suitable for the description of the morphology of the membranous labyrinth, 8 for counting Scarpa's ganglion cells, and 6 for measuring the densities of vestibular hair cells. The bones were fixed, cut, and stained according to previously published methods. Preferably, the implanted electrode was left in situ. Vestibular hair cells were counted with Nomarski's optics. Results: Differences in Scarpa's ganglion cell counts and hair cell densities between the implanted and nonimplanted sides were not statistically significant. In 59% of the implanted bones, the cochlea was hydropic, and in the majority of these bones the saccule was collapsed. Conclusion: Cochlear implantation does not cause deafferentation of the peripheral vestibular system. Cochlear hydrops accompanied by saccular collapse is common and may cause attacks of vertigo of delayed onset, similar to Meniere's syndrome as previously reported in several clinical series. Hydrops could be caused by obstruction of endolymphatic flow in the ductus reuniens or in the hook portion of the cochlea or by damage to the lateral cochlear wall caused by implantation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.liarvord.edu OI Handzel, Ophir/0000-0002-6905-3034 NR 28 TC 46 Z9 48 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2006 VL 27 IS 1 BP 57 EP 64 DI 10.1097/01.mao.0000188658.36327.8f PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 004AO UT WOS:000234724600011 PM 16371848 ER PT J AU Halpin, C Rauch, SD AF Halpin, C Rauch, SD TI Using audiometric thresholds and word recognition in a treatment study SO OTOLOGY & NEUROTOLOGY LA English DT Article DE audiometry; pure-tone average; hearing thresholds; word recognition AB Objectives: First, to examine a possible limit on significant results imposed by a progressive floor effect for hearing threshold improvement in a treatment study. This floor effect for hearing recovery suggests that if inclusion criteria are not set sufficiently high, the superiority of a treatment group may not be detectable. Second, to examine the outcomes when using two different types of criteria for significant change in a subject's word recognition score. Methods: Several single-number criteria (e.g., 15 percentage points) are compared with the 95% (p = 0.05) criteria from the binomial critical difference table for monosyllables. Critical differences for binomial variables change depending on whether the starting value lies in the middle (near 50% correct) or at either extreme of the range of scores (0 or 100%). Different judgments of significant word recognition improve- ment (or decrease) using binomial versus single-value criteria are presented. Data Source: A recent treatment study of sudden sensorineural hearing loss (n = 318) is used to illustrate these effects. Conclusion: First, there is a progressive floor effect of presenting severity that covaries with the outcome measure hearing threshold recovery. In some designs, this may act to constrain the ability to detect a significant difference. Second, in the example data set, the use of single-value criteria for significant within subject change in word recognition (e.g., 15 percentage points) introduced a miscategorization error rate of approximately 9% when compared with the result of the binomial 95% critical difference table. C1 Harvard Univ, Dept Audiol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Halpin, C (reprint author), Harvard Univ, Dept Audiol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM cfhalpin@meei.harvard.edu NR 8 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2006 VL 27 IS 1 BP 110 EP 116 DI 10.1097/00129492-200601000-00020 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 004AO UT WOS:000234724600020 PM 16371857 ER PT J AU Hess, DR AF Hess, Dean R. TI Monitoring during mechanical ventilation SO PAEDIATRIC RESPIRATORY REVIEWS LA English DT Article; Proceedings Paper CT 7th International Congress on Pediatric Pulmonology (CIPP VII) CY JUL 08-11, 2006 CL Montreal, CANADA ID INTENSIVE-CARE UNIT; PULSE OXIMETRY; PULMONARY MECHANICS C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM dhess@partners.org NR 23 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1526-0542 J9 PAEDIATR RESPIR REV JI Paediatr. Respir. Rev. PY 2006 VL 7 SU 1 BP S37 EP S38 DI 10.1016/j.prrv.2006.04.177 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 119JA UT WOS:000243007400013 PM 16798590 ER PT J AU Wang, SX Lim, G Yang, LL Sung, BK Mao, JR AF Wang, SX Lim, G Yang, LL Sung, BK Mao, JR TI Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats SO PAIN LA English DT Article DE neuropathic pain; allodynia; hyperalgesia; glucocorticoid receptor; glutamate transporter; EAAC1; nerve injury ID NF-KAPPA-B; AMINO-ACID TRANSPORTER; NEUROPATHIC PAIN; PERIPHERAL MONONEUROPATHY; ANTIINFLAMMATORY ACTION; MOLECULAR MECHANISMS; BASOLATERAL AMYGDALA; MORPHINE-TOLERANCE; NMDA RECEPTOR; P65 SUBUNIT AB Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2=0.5 mu g =vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappa B (NF-kappa B) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 =0.5 mu g = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappa B within the spinal cord dorsal horn. Since, NF-kappa B has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF- kappa B may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr,Dept Anesthesia & Crit Care,Div Pain, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr,Dept Anesthesia & Crit Care,Div Pain, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [DA08835]; NINDS NIH HHS [NS45681, R01 NS42661] NR 58 TC 29 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2006 VL 120 IS 1-2 BP 78 EP 85 DI 10.1016/j.pain.2005.10.015 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 009KP UT WOS:000235111100010 PM 16360273 ER PT S AU Oaklander, AL AF Oaklander, Anne Louise BE Cervero, F Jensen, TS TI Neuropathological examination of peripheral nerves in painful neuropathies (neuralgias) SO PAIN SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID SUPERFICIAL DORSAL HORN; SENSORY NEUROPATHY; POSTHERPETIC NEURALGIA; SPINAL-CORD; TRIGEMINAL NEURALGIA; DIABETIC NEUROPATHY; CUTANEOUS INNERVATION; FIBER DEGENERATION; PLEXUS NEUROPATHY; SCIATIC-NERVE C1 [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol, Nerve Injury Unit,Med Sch, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit,Med Sch, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Dept Neuropathol, Nerve Injury Unit,Med Sch, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Anesthesiol Neurol & Neuropathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol, Nerve Injury Unit,Med Sch, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM aoaklander@partners.org NR 72 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-08-054498-4 J9 HAND CLINIC PY 2006 VL 81 BP 463 EP 479 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA BCR19 UT WOS:000311077900034 PM 18808853 ER PT S AU Watson, CPN Oaklander, AL AF Watson, C. Peter N. Oaklander, Anne Louise BE Cervero, F Jensen, TS TI Postherpetic neuralgia SO PAIN SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID POST-HERPETIC NEURALGIA; PLACEBO-CONTROLLED TRIAL; PAINFUL DIABETIC-NEUROPATHY; RANDOMIZED CONTROLLED-TRIAL; LIDOCAINE PATCH 5-PERCENT; ENTRY ZONE LESIONS; DOUBLE-BLIND; TOPICAL LIDOCAINE; LONG-TERM; NERVE-FIBERS C1 [Watson, C. Peter N.] Univ Toronto, Toronto, ON, Canada. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Boston, MA USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Anesthesiol Neurol & Neuropathol, Boston, MA 02114 USA. RP Watson, CPN (reprint author), 1 Sir Williams Lane, Toronto, ON M9A 1T8, Canada. EM peter.watson@utoronto.ca NR 108 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-08-054498-4 J9 HAND CLINIC PY 2006 VL 81 BP 661 EP 677 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA BCR19 UT WOS:000311077900047 PM 18808866 ER PT J AU Surkan, PJ Dickman, PW Steineck, G Onelov, E Kreicbergs, U AF Surkan, PJ Dickman, PW Steineck, G Onelov, E Kreicbergs, U TI Home care of a child dying of a malignancy and parental awareness of a child's impending death SO PALLIATIVE MEDICINE LA English DT Article DE awareness; cancer; child; health care facilities; palliative care ID PALLIATIVE CARE; TERMINAL CARE; CANCER; DISEASE; LIFE; EXPERIENCES; PREVALENCE; NATIONWIDE; SYMPTOMS; ILLNESS AB In this population-based study, we found that parents who are aware that their child will die from a malignancy are more likely to care for their child at home during the child's last month of life compared to parents who are not aware. End-of-life home care was comparable to hospital care for satisfactory pain relief, access to pain relief and access to medications for other physical symptoms. Using an anonymous postal questionnaire, we obtained information from 449 parents in Sweden who had lost a child due to a malignancy between 1992 and 1997, 4 to 9 years before participating in our study. The prevalence of dying at home and being cared for at home during the last month of life was 23.7% when parents realized intellectually more than 1 month in advance that the child would die (versus 12% who did not), 28.7% for parents who sensed that the child was aware of his or her imminent death (versus 7.8% who did not sense this) and 21.9% for those who received information that the child's illness was incurable (versus 9.4% who did not receive the information). Prevalence of children's unrelieved pain was 11.6% for those receiving home care and 15.3% for those receiving care outside the home. C1 Karolinska Inst, Karolinska Hosp, Dept Oncol & Pathol, SE-17176 Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Karolinska Hosp, Dept Pathol & Oncol, S-10401 Stockholm, Sweden. Sahlgrenska Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA USA. Karolinska Hosp, Dept Women & Child Hlth, Stockholm, Sweden. RP Surkan, PJ (reprint author), Karolinska Inst, Karolinska Hosp, Dept Oncol & Pathol, Z5-U1, SE-17176 Stockholm, Sweden. EM psurkan@hsph.harvard.edu RI Dickman, Paul/B-4572-2013; OI Dickman, Paul/0000-0002-5788-3380; Steineck, Gunnar/0000-0002-0787-3969 NR 24 TC 29 Z9 29 U1 1 U2 3 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2006 VL 20 IS 3 BP 161 EP 169 DI 10.1191/0269216306pm1139oa PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 038MD UT WOS:000237224300002 PM 16764220 ER PT J AU Hunt, H Valdimarsdottir, U Mucci, L Kreicbergs, U Steineck, G AF Hunt, Hayley Valdimarsdottir, Unnur Mucci, Lorelei Kreicbergs, Ulrika Steineck, Gunnar TI When death appears best for the child with severe malignancy: a nationwide parental follow-up SO PALLIATIVE MEDICINE LA English DT Article DE end-of-life; malignancy; morbidity; palliative; parents; pediatric ID PEDIATRIC ONCOLOGY; DECISION-MAKING; CANCER; LIFE; ADOLESCENTS; ANXIETY; GENDER; END AB Background: Loss of a child to malignancy is associated with long-term morbidity among surviving parents. This study aims to identify particular sources of stress among parents of children with severe malignancy. Methods: We attempted to contact all parents in Sweden who lost a child to cancer between 1992 and 1997. Some 449 parents answered an anonymous questionnaire, including a question regarding whether they ever thought that death would be best for the child with severe malignancy. Results: Mothers whose children were unable to communicate during their last week of life were more likely to think that death would be best for the child (relative risk (RR): 1.6; 95% confidence interval (CI): 1.2-2.1). Fathers whose children faced six years or more with malignancy were more likely to think that death would be best for their child (RR: 2.1; 95% CI: 1.3-3.5). Conclusions: The inability of the child with severe malignancy to communicate increases the likelihood of mothers thinking that death would be best for the child, while longer duration of the child's illness increases the occurrence of this thought among fathers. C1 Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Karolinska Inst, Dept Women & Child Hlth, Stockholm, Sweden. Phyllis F Cantor Ctr, Dana Farber Canc Inst, Boston, MA USA. Sahlgrenska Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden. RP Hunt, H (reprint author), Karolinska Inst, Karolinska Hosp, Dept Pathol & Oncol, Div Clin Canc Epidemiol, Z5-U1, SE-17176 Stockholm, Sweden. EM hayley.hunt@ki.se OI Steineck, Gunnar/0000-0002-0787-3969 NR 23 TC 6 Z9 6 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2006 VL 20 IS 6 BP 567 EP 577 DI 10.1177/0269216306069671 PG 13 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 094ZV UT WOS:000241278900002 PM 17060249 ER PT J AU Grunfeld, E Lethbridge, L Dewar, R Lawson, B Paszat, LF Johnston, G Burge, F McIntyre, P Earle, CC AF Grunfeld, Eva Lethbridge, Lynn Dewar, Ron Lawson, Beverley Paszat, Lawrence F. Johnston, Grace Burge, Frederick McIntyre, Paul Earle, Craig C. TI Towards using administrative databases to measure population-based indicators of quality of end-of-life care: testing the methodology SO PALLIATIVE MEDICINE LA English DT Article DE health services; palliative care; quality indicators ID CANCER CARE; HEALTH-CARE; BREAST-CANCER; IDENTIFICATION; AGENDA AB This study is concerned with methods to measure population-based indicators of quality end-of-life care. Using a retrospective cohort approach, we assessed the feasibility, validity and reliability of using administrative databases to measure quality indicators of end-of-life care in two Canadian provinces. The study sample consisted of all females who died of breast cancer between 1 January 1998 and 31 December 2002, in Nova Scotia or Ontario, Canada. From an initial list of 19 quality indicators selected from the literature, seven were determined to be fully measurable in both provinces. An additional seven indicators in one province and three in the other province were partially measurable. Tests comparing administrative and chart data show a high level of agreement with inter-rater reliability, confirming consistency in the chart abstraction process. Using administrative data is an efficient, population-based method to monitor quality of care which can compliment other methods, such as qualitative and purposefully collected clinical data. C1 Canc Care Nova Scotia, Canc Outcomes Res Program, Halifax, NS B3H 2Y9, Canada. Dalhousie Univ, Div Med Oncol, Halifax, NS, Canada. Canc Care Nova Scotia, Surveillance & Epidemiol Unit, Halifax, NS, Canada. Dalhousie Univ, Dept Family Med, Halifax, NS, Canada. Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. Dalhousie Univ, Sch Hlth Serv Adm, Halifax, NS, Canada. Dalhousie Univ, Div Palliat Med, Halifax, NS, Canada. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Grunfeld, E (reprint author), Canc Care Nova Scotia, Canc Outcomes Res Program, 1278 Tower Route,5th Floor,Bethune Bldg, Halifax, NS B3H 2Y9, Canada. EM eva.grunfeld@ccns.nshealth.ca FU Canadian Institutes of Health Research [80067-1] NR 48 TC 74 Z9 75 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2006 VL 20 IS 8 BP 769 EP 777 DI 10.1177/0269216306072553 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 122UA UT WOS:000243251300006 PM 17148531 ER PT J AU Koropchak, CM Pollak, KI Arnold, RM Alexander, SC Skinner, CS Olsen, MK Jeffreys, AS Rodriguez, KL Abernethy, AP Tulsky, JA AF Koropchak, Celine M. Pollak, Kathryn I. Arnold, Robert M. Alexander, Stewart C. Skinner, Celette Sugg Olsen, Maren K. Jeffreys, Amy S. Rodriguez, Keri L. Abernethy, Amy P. Tulsky, James A. TI Studying communication in oncologist-patient encounters: The SCOPE trial SO PALLIATIVE MEDICINE LA English DT Article DE patient-provider relationship; physician-patient communication; oncologist ID CANCER-PATIENTS; PRIMARY-CARE; SKILLS; DEPRESSION; QUALITY; MODEL AB Study objective: Most oncologists have not received adequate training in physician-patient communication, and existing effective courses tend to be time and resource intensive. We are developing and testing a tailored CD-ROM educational intervention that includes feedback on oncologists' own audio-recorded conversations with their advanced cancer patients. In this report, we describe the study methods and identify challenges to implementation and how these were overcome. Study design: A three-phase, randomized, controlled trial. In Phase 1, we audio-recorded oncologist-patient clinic encounters. In Phase 2, oncologists were randomly assigned to a communication CD-ROM intervention or control. Phase 3 consisted of audio-recording all participating oncologists conversing with a new sample of patients, two to 12 months after the intervention, to assess its effectiveness. Setting: Oncology clinics at Duke University Medical Center (DUMC) and the Durham Veterans Affairs Medical Center (DVAMC) in Durham, NC, and the University of Pittsburgh Medical Center (UPMC) in Pittsburgh, PA. Participants: Medical, radiation and gynecological oncologists and their patients with advanced cancer. Intervention: A tailored CD-ROM that contains an interactive educational interface with reference materials and video-clips of model conversations, along with the oncologists' own Phase 1 audio-recorded conversations. Conclusion: We present challenges and solutions to oncologist recruitment, identifying appropriate patients with advanced cancer, adapting to clinic flow, and developing a self-administered communications intervention. C1 Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Univ Pittsburgh, Inst Canc, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Inst Doctor Patient Commun, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Inst Enhance Palliat Care, Pittsburgh, PA 15260 USA. Durham VA Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27706 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Koropchak, CM (reprint author), Duke Univ, Med Ctr, Ctr Palliat Care, Box 2720,2424 Erwin Rd,Suite 1105, Durham, NC 27705 USA. EM korop001@mc.duke.edu FU NCI NIH HHS [R01 CA-100387-01] NR 29 TC 27 Z9 27 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2006 VL 20 IS 8 BP 813 EP 819 DI 10.1177/0269216306070657 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 122UA UT WOS:000243251300011 PM 17148536 ER PT J AU Tanaka, M Chari, S Adsay, V Fernandez-del Castillo, C Falconi, M Shimizu, M Yamaguchi, K Yamao, K Matsuno, S AF Tanaka, Masao Chari, Suresh Adsay, Volkan Fernandez-del Castillo, Carlos Falconi, Massimo Shimizu, Michio Yamaguchi, Koji Yamao, Kenji Matsuno, Seiki TI International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas SO PANCREATOLOGY LA English DT Review DE intraductal papillary mucinous neoplasm; mucinous cystic neoplasm; guidelines for management of IPMN/MCN; pancreatic neoplasm; pancreatectomy ID MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; BRANCH DUCT TYPE; DISTAL PANCREATECTOMY; INTRAEPITHELIAL NEOPLASIA; PERORAL PANCREATOSCOPY; NATURAL-HISTORY; CLINICOPATHOLOGICAL FEATURES; MR CHOLANGIOPANCREATOGRAPHY; DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC RETROGRADE AB Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology. Copyright (C) 2006 S. Karger AG, Basel and IAP. C1 Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. Mayo Clin, Dept Gastroenterol, Rochester, MN USA. Wayne State Univ, Dept Pathol, Detroit, MI USA. Wayne State Univ, Harper Hosp, Karmanos Canc Ctr, Detroit, MI USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA USA. Univ Verona, Dept Surg, I-37100 Verona, Italy. Saitama Med Sch, Dept Pathol, Saitama, Japan. Aichi Canc Ctr, Dept Gastroenterol, Nagoya, Aichi 464, Japan. Tohoku Univ, Dept Surg Gastroenterol, Grad Sch Med, Sendai, Miyagi 980, Japan. RP Tanaka, M (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. EM masaotan@med.kyushu-u.ac.jp OI Falconi, Massimo/0000-0001-9654-7243 NR 86 TC 939 Z9 991 U1 6 U2 34 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2006 VL 6 IS 1-2 BP 17 EP 32 DI 10.1159/000090023 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 136XF UT WOS:000244256700006 PM 16327281 ER PT J AU Schneider, A Lamb, J Barmada, MM Cuneo, A Money, ME Whitcomb, DC AF Schneider, Alexander Lamb, Janette Barmada, M. Michael Cuneo, Anthony Money, Mary E. Whitcomb, David C. TI Keratin 8 mutations are not associated with familial, sporadic and alcoholic pancreatitis in a population from the United States SO PANCREATOLOGY LA English DT Article DE keratin 8; hereditary pancreatitis; alcoholic pancreatitis; chronic pancreatitis ID TROPICAL CALCIFIC PANCREATITIS; CATIONIC TRYPSINOGEN GENE; SERINE-PROTEASE INHIBITOR; CYSTIC-FIBROSIS GENE; SPINK1/PSTI MUTATIONS; LIVER-DISEASE; KAZAL TYPE-1; POLYMORPHISMS; BANGLADESH; HEALTH AB Background and Aims: Genetic predispositions play a major role in the development of chronic pancreatitis. Recently, a mutation in the keratin 8 gene (G62C) was reported to be associated with chronic pancreatitis in Italy. We determined whether mutations in the keratin 8 gene are associated with familial, sporadic and alcoholic recurrent acute or chronic pancreatitis in a population from the United States. Methods: We investigated the relevant genomic region of the keratin 8 gene in 80 patients with familial pancreatitis without a cationic trypsinogen (PRSS1) gene mutation from 52 different families, 21 patients with familial hereditary pancreatitis and a PRSS1 mutation from 20 different families, 126 patients with sporadic pancreatitis without a PRSS1 mutation, 61 patients with alcoholic pancreatitis and 271 controls by direct DNA sequencing. Results: We found the heterozygous G62C mutation in n = 3/80 patients ( n = 2/52 patients from different families, 3.8%) with familial pancreatitis without PRSS1 mutation and in n = 3/126 patients (2.4%) with sporadic pancreatitis. We detected an adjacent heterozygous I63V mutation in n = 2/80 patients ( n = 2/52 patients from different families, 3.8%) with familial pancreatitis without PRSS1 mutation and in n = 1/61 patients (1.6%) with alcoholic pancreatitis. We found the G62C mutation in n = 2/271 controls (0.7%) and the I63V mutation in n = 2/271 controls ( 0.7%). There were no statistically signifi cant differences in the genotype frequencies between patients and controls ( p >0.05). Screening of additional available family members revealed that these variants did not segregate with the disease phenotype. There was no statistically signifi cant difference in the frequency of these keratin 8 variants between patients with chronic pancreatitis and controls ( p >0.05). Conclusion: These keratin 8 variants are not associated with familial, sporadic or alcoholic pancreatitis. Copyright (C) 2006 S. Karger AG, Basel and IAP. C1 Univ Pittsburgh, UPMC Presbyterian, Ctr Genom Sci, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Dept Med, Div Gastroenterol, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Dept Human Genet, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Washington Cty Hosp, Hagerstown, MD USA. Univ Heidelberg Hosp, Dept Med 2, D-68135 Mannheim, Germany. RP Whitcomb, DC (reprint author), Univ Pittsburgh, UPMC Presbyterian, Ctr Genom Sci, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM whitcomb@pitt.edu OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 22 TC 7 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2006 VL 6 IS 1-2 BP 103 EP 108 DI 10.1159/000090029 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 136XF UT WOS:000244256700014 PM 16327287 ER PT J AU Fernandez-del Castillo, C AF Fernandez-del Castillo, Carlos TI Frozen section diagnosis of pancreatic malignancy: A sensitive diagnostic technique - Invited commentary - To freeze or not to freeze ... Is that still a question? SO PANCREATOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2006 VL 6 IS 3 BP 214 EP 214 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 136XI UT WOS:000244257000009 ER PT J AU Weintraub, D Morales, KH Duda, JE Moberg, PJ Stern, MB AF Weintraub, Daniel Morales, Knashawn H. Duda, John E. Moberg, Paul J. Stern, Matthew B. TI Frequency and correlates of co-morbid psychosis and depression in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; depression; psychosis; co-morbidity ID RATING-SCALE; RISK-FACTORS; TEACHING TAPE; MOTOR SECTION; HALLUCINATIONS; PREVALENCE; DELUSIONS AB Though both psychosis and depression are common in Parkinson's disease (PD), it is not clear if an association between the two disorders exists. One hundred and thirty PD patients were divided into four groups based on a comprehensive psychiatric assessment: (1) no depression or psychosis (47.7%); (2) psychosis only (16.2%); (3) depression only (26.2%); and (4) psychosis and depression (10.0%). Co-morbid psychosis and depression did not occur more frequently than expected by chance (P = .77). Psychosis was associated with dopamine agonist use (P = .02), depression with mild-cognitive impairment (P = .03), and their co-occurrence with higher daily levodopa dosages (P < .01). These results suggest that psychosis and depression in PD are distinct neurobehavioral disorders. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04]; PHS HHS [067894] NR 31 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2006 VL 12 IS 7 BP 427 EP 431 DI 10.1016/j.parkreldis.2006.03.006 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 099OW UT WOS:000241605700004 PM 16797214 ER PT J AU Beheshti, J Mark, EJ Akbaei, HMH Aslani, J Ghanei, M AF Beheshti, Javad Mark, Eugene J. Akbaei, Hassan Mohammad Hosein Aslani, Jafar Ghanei, Mostafa TI Mustard lung secrets: Long term clinicopathological study following mustard gas exposure SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE sulfur mustard; chronic lung disease; bronchiolitis obliterans organizing pneumonia; organizing pneumonia; chemical warfare ID BRONCHIOLITIS OBLITERANS; SULFUR MUSTARD; ORGANIZING PNEUMONIA; PULMONARY-FIBROSIS; CT; INHALATION; STATEMENT; DISEASES AB Considering the undefinite nature of lung pathology in patients exposed to sulfur mustard (SM) many years after exposure, we conducted this study to document and quantify lung disease in this setting. In a cross sectional study, we selected 23 patients exposed to SM gas approximately 14 years ago during the Iran-Iraq war (1980-1988). We studied their clinical history, physical examination, pulmonary function test (PFT), high-resolution computed tomography scan (HRCT) of the chest, bronchoscopy, and bronchoalveolar lavage (BAL) sampling, and transbronchial lung biopsies. Other potential causes of lung disease, including smoking of cigarettes, were excluded. All 23 patients were symptomatic with cough, dyspnea, and/or felt tight in the chest. All of them had significant air trapping in HRCT and a marked increase of residual volume in PFT. The most common inflammatory cell in BAL fluid was neutrophil (88%). Of the 23 cases, there was sufficient tissue for detailed evaluation in 22. Histologically, 11 cases showed airway epithelial injury, and nine of the 14 lung biopsies with alveoli had histopathological changes diagnosable as organizing pneumonia (OP) or bronchiolitis obliterans OP (BOOP). Two out of 14 cases showed changes suggestive of OP. Inhalation of SM can lead to persistant and clinically significant lung disease, including bronchial mucosal injury and OP, many years after exposure. (c) 2006 Elsevier GmbH. All rights reserved. C1 Baqiyatallah Med Sci Univ, Chem Injured Res Ctr, Tehran, Iran. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ghanei, M (reprint author), Baqiyatallah Med Sci Univ, Chem Injured Res Ctr, Mollasadra St,Postal Code 14359151371, Tehran, Iran. EM m.ghanei@bmsu.ac.ir NR 24 TC 49 Z9 51 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2006 VL 202 IS 10 BP 739 EP 744 DI 10.1016/j.prp.2006.04.008 PG 6 WC Pathology SC Pathology GA 098CO UT WOS:000241498800006 PM 16887283 ER PT J AU Waber, DP Pomeroy, SL Chiverton, AM Kieran, MW Scott, RM Goumnerova, LC Rivkin, MJ AF Waber, DP Pomeroy, SL Chiverton, AM Kieran, MW Scott, RM Goumnerova, LC Rivkin, MJ TI Everyday cognitive function after craniopharyngioma in childhood SO PEDIATRIC NEUROLOGY LA English DT Article ID TEMPORAL-LOBE; MEMORY; CHILDREN; DEFICITS; COMPLAINTS AB Despite clinical impressions that cognitive complaints are prominent in patients with a history of craniopharyngioma, formal neuropsychologic documentation is inconsistent. This study assessed everyday cognitive complaints and neuropsychologic test performance to evaluate the prevalence of problems and the relationship of these domains to one another in patients treated for craniopharyngiorna in childhood or adolescence. Ten patients treated for craniopharyngioma completed measures of everyday cognitive function (Cognitive Failures Questionnaire, Rivermead Behavioural Memory Test) and a battery of standard neuropsychologic tests. The prevalence of problems was ascertained for each measure. Most patients demonstrated significant deficits in everyday memory (Cognitive Failures Questionnaire, 9/10 patients; Rivermead Behavioural Memory Test, 7/10 patients). Scores were within normal limits, however, for intelligence quotient, achievement, attention, verbal memory, and spatial working memory. Processing speed was slow (5110 patients). Spatial working memory predicted Cognitive Failures Questionnaire (P < 0.07), as did somatic symptoms from the Beck Depression Inventory (P < 0.01), but these associations appeared independent. Adolescents and young adults with treated craniopharyngioma experience deficits in everyday cognitive functions, many involving memory, that are not easily detected by standard neuropsychologic testing. The extent of self-rated cognitive problems is related to spatial working memory and somatic concerns. (c) 2006 by Elsevier Inc. All rights reserved. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Waber, DP (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. EM deborah.waber@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU NICHD NIH HHS [P30-HD18655] NR 35 TC 28 Z9 31 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JAN PY 2006 VL 34 IS 1 BP 13 EP 19 DI 10.1016/j.pediatrneurol.2005.06.002 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 003DA UT WOS:000234660600003 PM 16376272 ER PT J AU Savidge, TC Newman, PG Pan, WH Weng, MQ Shi, HN McCormick, BA Quaroni, A Walker, WA AF Savidge, TC Newman, PG Pan, WH Weng, MQ Shi, HN McCormick, BA Quaroni, A Walker, WA TI Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling SO PEDIATRIC RESEARCH LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; TOLL-LIKE RECEPTORS; CROSS-TOLERANCE; GENE-EXPRESSION; LIPOTEICHOIC ACID; INDUCTION; ENDOTOXIN; PATHWAYS; HYPORESPONSIVENESS; DIFFERENTIATION AB Intestinal epithelial cells (IEC) are constantly exposed to bacterial components, such as LPS, without triggering proinflammatory immune responses.. This study demonstrates that chronic exposure of human-derived IEC to LPS induces tolerance to an endogenous inflammatory cytokine (1L-1 beta) activated IL-8 response that Occurs independently of TLR-4/MD-2 signaling. IL-8 production in response to activation by unrelated TNF-alpha and PMA signaling pathways is also inhibited, indicating a broad-spanning tolerance. Quantitative rtPCR and IL-8 promoter-luciferase assays demonstrate that tolerance is regulated at the transcriptional level and occurs independently of IEC cytodifferentiation. By contrast, LPS does not significantly alter other proinflammatory signaling cascades in IEC that function independently of IL-8 production, e.g., IL-6 secretion and PEEC (Hepoxilin A3)-induced neutrophil transepithelial migration in response to invasive Salmonella typhimurium. Human IEC have therefore developed LPS-induced signaling cascades that promote an IL-8 hyporesponsiveness to proinflammatory cytokines while LPS exposure does not compromise the ability of IEC to mount other proinflammatory immune responses to invasive enteropathogens. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Cornell Univ, Physiol Sect, Ithaca, NY 14853 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, 114 16th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R37 HD012437, R37 HD12437]; NIDDK NIH HHS [R01 DK70260, R01 DK070260, P01 DK33506, P30 DK40561, P30 DK040561-10, P30 DK040561, P01 DK033506] NR 31 TC 21 Z9 29 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2006 VL 59 IS 1 BP 89 EP 95 DI 10.1203/01.pdr.0000195101.74184.e3 PG 7 WC Pediatrics SC Pediatrics GA 997UY UT WOS:000234275500018 PM 16326999 ER PT J AU Kooijman, AC Cornelissen, FW Dryja, TP Pott, JWR AF Kooijman, A. C. Cornelissen, F. W. Dryja, T. P. Pott, J. W. R. TI Impaired perception of moving high-contrast and low-contrast optotypes by bradyopsia patients lacking RGS9 SO PERCEPTION LA English DT Meeting Abstract C1 Univ Groningen, Med Ctr, Dept Ophthalmol, NL-9700 RB Groningen, Netherlands. Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. EM a.kooijman@ohk.umcg.nl NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2006 VL 35 SU S BP 129 EP 130 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 127PR UT WOS:000243599300410 ER PT J AU Rudolph, JL Tilahun, D Treanor, PR Pochay, VE Mahendrakar, MA Sagar, P Babikian, VL AF Rudolph, JL Tilahun, D Treanor, PR Pochay, VE Mahendrakar, MA Sagar, P Babikian, VL TI Use of a large bore syringe creates significantly fewer high intensity transient signals (HITS) into a cardiopulmonary bypass system than a small bore syringe SO PERFUSION-UK LA English DT Article ID CEREBRAL MICROEMBOLISM; CAROTID-ENDARTERECTOMY; ASSOCIATION; SURGERY; STROKE AB Introduction: High intensity transient signals (HITS) have been reported to occur following perfusionist intervention during cardiac surgery. This study investigates the relationship of the syringe bore, injection rate, and HITS created. Methods: Syringes (10 mL) with a male luer-lock connection (Large Bore) and Abboject 'jet syringes' with a 20 GA needle and male luer-lock connector (Small Bore) were filled with 10 mL, of 0.9 N saline. A perfusionist was randomly assigned a set of four similar syringes followed by the other syringe bore. Each of the four syringes was injected into an in vitro saline-primed cardiopulmonary bypass (CPB) system over 5, 10, 15, or 20 sec. Sixteen randomizations of small and large bore syringes were completed at the four injection times (128 injections). HITS in the CPB arterial line were detected with transcranial Doppler (TCD) probes, were recorded for the 2 min following the injection, and were counted independently off-line by two reviewers. Results: The use of a large bore syringe compared to a small bore syringe created significantly fewer HITS (29+/-6 versus 145+/-17 [mean+/-SEM], p <0.001) introduced into the CPB arterial line. Injection over a longer time produced significantly fewer HITS than shorter injection times (p <0.001). Conclusion: Significantly fewer HITS are introduced into the CPB system by using standard syringes and slower injection time. C1 VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. VA Boston Healthcare Syst, Dept Cardiac Surg, Boston, MA USA. VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Rudolph, JL (reprint author), VA BHS, GRECC JP182, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU NIA NIH HHS [5 K12 AG00294-18] NR 16 TC 4 Z9 4 U1 2 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0267-6591 J9 PERFUSION-UK JI Perfusion-UK PY 2006 VL 21 IS 1 BP 67 EP 71 DI 10.1191/0267659106pf843oa PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 011PQ UT WOS:000235281000010 PM 16485702 ER PT J AU Valeri, CR MacGregor, H Ragno, G Healey, N Fonger, J Khuri, SF AF Valeri, C. R. MacGregor, H. Ragno, G. Healey, N. Fonger, J. Khuri, S. F. TI Effects of centrifugal and roller pumps on survival of autologous red cells in cardiopulmonary bypass surgery SO PERFUSION-UK LA English DT Article ID LACTATE DEHYDROGENASE; MEGALOBLASTIC ANAEMIA; BLOOD-CELLS; VOLUME; VIVO AB Background: Either a roller pump or a centrifugal pump can be used in the extracorporeal circuit during surgery with cardiopulmonary bypass. In this study, we assessed the effect of these two pumps on the 24-h post-transfusion survival values of autologous red blood cells (RBC). Study design and methods: Fourteen male patients subjected to extracorporeal bypass procedures were studied. In seven patients, the autologous red cells were collected following the cardiopulmonary bypass procedure using the roller pump, and in seven patients, autologous red cells were collected following the cardiopulmonary procedure using the centrifugal pump. The 24-h post-transfusion survival values of the autologous RBC were measured using the 51 disodium chromate/99m technetium double isotope procedure. The effects of the extracorporeal bypass procedures using the roller pump and the centrifugal pump were also assessed by the measurements of hematocrit, platelet count, plasma hemoglobin, and serum lactate dehydrogenase levels. Results: The 51 disodium chromate 24-h post-transfusion survival values of the autologous RBC were similar whether the roller pump or the centrifugal pump was used in the extracorporeal. circulation, as were the hematocrit, platelet count, plasma hemoglobin and serum lactate dehydrogenase levels. Conclusion: The 24-h post-transfusion survival values of autologous RBC, measured by the 51 disodium chromate/99m technetium double isotope procedure, were not significantly different, whether the roller pump or the centrifugal pump was used in the extracorporeal circuit using membrane oxygenators during cardiopulmonary surgical procedures. C1 USN, Blood Res Lab, Boston, MA USA. Boston VA Healthcare Syst, W Roxbury Div, Boston, MA USA. RP Valeri, CR (reprint author), NBRL Inc, 195 Bournehurst Dr, Plymouth, MA 02360 USA. EM navblood@nbrl.org NR 16 TC 16 Z9 19 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0267-6591 J9 PERFUSION-UK JI Perfusion-UK PY 2006 VL 21 IS 5 BP 291 EP 296 DI 10.1177/0267659106073976 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 118KD UT WOS:000242940300008 PM 17201084 ER PT J AU Karnon, J Delea, T Johnston, SRD Smith, R AF Karnon, J Delea, T Johnston, SRD Smith, R TI Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy - The UK perspective SO PHARMACOECONOMICS LA English DT Article ID ISOLATED LOCOREGIONAL RECURRENCE; EARLY BREAST-CANCER; PHASE-III; CHEMOTHERAPY; MASTECTOMY AB Background: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrolment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. Methods: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. Results: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pound per patient (10 pound 833 letrozole vs 7101 pound with no therapy). Cost effectiveness was estimated at 10 pound 338 per QALY gained (95% CI 5276, 43 828). The results were robust to sensitivity analyses. Conclusion: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy. C1 Univ Sheffield, Sch Hlth & Related Res, Sheffield S1 4DA, S Yorkshire, England. Policy Anal Inc, Brookline, MA USA. Royal Marsden Hosp, London SW3 6JJ, England. S Carolina Oncol Associates, Columbia, SC USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Karnon, J (reprint author), Univ Sheffield, Sch Hlth & Related Res, Regent St, Sheffield S1 4DA, S Yorkshire, England. EM j.karnon@sheffield.ac.uk NR 24 TC 31 Z9 32 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2006 VL 24 IS 3 BP 237 EP 250 DI 10.2165/00019053-200624030-00004 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 026TB UT WOS:000236364100004 PM 16519546 ER PT J AU Furuno, JP Metlay, JP Harnett, JP Wilson, J Langenberg, P McGregor, JC Zhu, JK Perencevich, EN AF Furuno, JP Metlay, JP Harnett, JP Wilson, J Langenberg, P McGregor, JC Zhu, JK Perencevich, EN TI Population antibiotic susceptibility for Streptococcus pneumoniae and treatment outcomes in common respiratory tract infections SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE Streptococcus pneumoniae; ecological analysis; respiratory tract infection; antibiotic resistance; outcomes ID ACUTE OTITIS-MEDIA; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL RESISTANCE; UNITED-STATES; MANAGED CARE; CLINICAL OUTCOMES; ACUTE SINUSITIS; IMPACT; TRENDS; EXACERBATIONS AB Purpose Antibiotic-resistant Streptococcus pneumoniae potentially threatens the successful treatment of common respiratory tract infections (RTls); however, the relationship between antibiotic resistance and treatment outcomes remains unclear. We aimed to test the hypothesis that higher in vitro penicillin and erythromycin nonsusceptibility levels among clinical isolates of S. pneumoniae are associated with higher risk of treatment failure in suppurative acute otitis media (AOM), acute sinusitis, and acute exacerbation of chronic bronchitis (AECB). Methods We conducted a population-level analysis using treatment outcomes data from a national, managed-care claims database, and antibiotic susceptibility data from a national repository of antimicrobial susceptibility results between 1997 and 2000. Treatment outcomes in patients with suppurative AOM, acute sinusitis, or AECB receiving selected macrolides or beta-lactams were assessed. Associations between RTI-specific treatment outcomes and antibiotic nonsusceptibility were determined using Spearman correlation coefficients with condition-specific paired outcome and susceptibility data for each region and each year. Results There were 649 552 available RTI outcomes and 7252 susceptibility tests performed on S. pneumoniae isolates. There were no statistically significant trends across time for resolution proportions following treatment by either beta-lactams or macrolides among any of the RTIs. Correlation analyses found no statistically significant association between S. pneumoniae susceptibility and RTI treatment outcomes apart from a significant positive association between of erythromycin nonsusceptibility in ear isolates and macrolide treatment resolution for suppurative AOM. Conclusion On the population level, in vitro S. pneumoniae nonsusceptibility to macrolide or beta-lactam antibiotics was not associated with treatment failure in conditions of probable S. pneumoniae etiology. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Pfizer Inc, US Outcomes Res Grp, New York, NY USA. NIH, Natl Ctr Minor Hlth & Hlth Disparities, Bethesda, MD 20892 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. VA Maryland Healthcare Syst, Baltimore, MD USA. RP Furuno, JP (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 100 N Greene St,Lower Level, Baltimore, MD 21201 USA. RI McGregor, Jessina/A-7625-2008 NR 39 TC 6 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2006 VL 15 IS 1 BP 1 EP 9 DI 10.1002/pds.1135 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 006CO UT WOS:000234872900001 PM 16136615 ER PT J AU Sands, BE Duh, MS Cali, C Ajene, A Bohn, RL Miller, D Cole, JA Cook, SF Walker, AM AF Sands, BE Duh, MS Cali, C Ajene, A Bohn, RL Miller, D Cole, JA Cook, SF Walker, AM TI Algorithms to identify colonic ischemia, complications of constipation and irritable bowel syndrome in medical claims data: development and validation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE automated databases; colonic ischemia; constipation; irritable bowel syndrome; epidemiology ID PREVALENCE; DATABASES; CRITERIA AB Purpose A challenge in the use of insurance claims databases for epidemiologic research is accurate identification and verification of medical conditions. This report describes the development and validation of claims-based algorithms to identify colonic ischemia, hospitalized complications of constipation, and irritable bowel syndrome (IBS). Methods From the research claims databases of a large healthcare company, we selected at random 120 potential cases of IBS and 59 potential cases each of colonic ischemia and hospitalized complications of constipation. We sought the written medical records and were able to abstract 107, 57, and 51 records, respectively. We established a 'true' case status for each subject by applying standard clinical criteria to the available chart data. Comparing the insurance claims histories to the assigned case status, we iteratively developed, tested, and refined claims-based algorithms that would capture the diagnoses obtained from the medical records. We set goals of high specificity for colonic ischemia and hospitalized complications of constipation, and high sensitivity for IBS. Results The resulting algorithms substantially improved on the accuracy achievable from a naive acceptance of the diagnostic codes attached to insurance claims. The specificities for colonic ischemia and serious complications of constipation were 87.2 and 92.7%, respectively, and the sensitivity for IBS was 98.9%. Conclusions U.S. commercial insurance claims data appear to be usable for the study of colonic ischemia, IBS, and serious complications of constipation. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ingenix, Auburndale, MA USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 100 Charles River Plaza,9th Floor,165 Cambridge S, Boston, MA 02114 USA. EM bsands@partners.org FU NIDDK NIH HHS [K23 DK02850] NR 14 TC 12 Z9 12 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2006 VL 15 IS 1 BP 47 EP 56 DI 10.1002/pds.1118 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 006CO UT WOS:000234872900006 PM 15915441 ER PT J AU Pawlyk, AC Sanford, LD Brennan, FX Morrison, AR Ross, RJ AF Pawlyk, AC Sanford, LD Brennan, FX Morrison, AR Ross, RJ TI Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep SO PHARMACOLOGICAL REPORTS LA English DT Article DE amygdala; corticotropin-releasing factor; stress; psychological; sleep; REM ID FACTOR-RECEPTOR; STRESS; RAT; IMMOBILIZATION; LOCALIZATION; EMOTION; BRAIN; CRH AB Psychological stressors have a prominent effect on rapid eye movement sleep (REMS) in humans and animals. We hypothesized that the stress-related neurochemical corticotropin-releasing factor (CRF), acting in the amygdala, could initiate neural events that lead to REMS alterations. Therefore, we made bilateral microinjections of three different doses of CRF into the central nucleus of the amygdala (CeA) in five rats. Only the lowest dose of CRF (1 ng) induced a change in sleep, specifically REMS, during the 4-h post-injection period. Thus, REMS alterations following psychological stress may depend, in part, on CRF release in the CeA. C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Behav Hlth Serv 116 MHC, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Dept Anat & Pathol, Norfolk, VA 23501 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Ross, RJ (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. EM ross_r@mail.trc.upenn.edu FU NHLBI NIH HHS [HL7953]; NIMH NIH HHS [MH42903] NR 20 TC 11 Z9 11 U1 0 U2 1 PU POLISH ACAD SCIENCES INST PHARMACOLOGY PI KRAKOW PA SMETNA 12, 31-343 KRAKOW, POLAND SN 1734-1140 J9 PHARMACOL REP JI Pharmacol. Rep. PD JAN-FEB PY 2006 VL 58 IS 1 BP 125 EP 130 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 029HY UT WOS:000236554200017 PM 16531640 ER PT J AU van den Brink, GR Peppelenbosch, MP Roberts, DJ AF van den Brink, Gijs R. Peppelenbosch, Maikel P. Roberts, Drucilla J. BE Johnson, LR TI Hedgehog Signaling in Gastrointestinal Morphogenesis and Morphostasis SO PHYSIOLOGY OF THE GASTROINTESTINAL TRACT, VOLS 1 AND 2, 4TH EDITION LA English DT Article; Book Chapter ID KINESIN-RELATED PROTEIN; HUMAN SONIC HEDGEHOG; GROWTH-FACTOR-ALPHA; PANCREAS DEVELOPMENT; VACTERL-ASSOCIATION; MENETRIERS-DISEASE; COLORECTAL-CANCER; CUBITUS-INTERRUPTUS; POLARIZING ACTIVITY; ESOPHAGEAL ATRESIA C1 [van den Brink, Gijs R.] Univ Amsterdam, Acad Med Ctr, Lab Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. [Peppelenbosch, Maikel P.] Univ Groningen, Dept Cell Biol, NL-9713 AV Groningen, Netherlands. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP van den Brink, GR (reprint author), Univ Amsterdam, Acad Med Ctr, Lab Expt Internal Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 114 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045615-7 PY 2006 BP 271 EP 285 PG 15 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA BCR99 UT WOS:000311229600011 ER PT J AU Tache, Y Million, M AF Tache, Yvette Million, Mulugeta BE Johnson, LR TI Central Corticotropin-Releasing Factor and the Hypothalamic-Pituitary-Adrenal Axis in Gastrointestinal Physiology SO PHYSIOLOGY OF THE GASTROINTESTINAL TRACT, VOLS 1 AND 2, 4TH EDITION LA English DT Article; Book Chapter ID GASTRIC-ACID-SECRETION; IRRITABLE-BOWEL-SYNDROME; CENTRAL-NERVOUS-SYSTEM; STRESS-RELATED ALTERATIONS; EDINGER-WESTPHAL NUCLEUS; COLONIC MOTOR FUNCTION; FACTOR CRF RECEPTOR; MESSENGER-RNA EXPRESSION; WATER-AVOIDANCE STRESS; DORSAL VAGAL COMPLEX C1 [Tache, Yvette; Million, Mulugeta] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Tache, Yvette; Million, Mulugeta] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Med,Div Digest Dis, Los Angeles, CA 90095 USA. [Tache, Yvette; Million, Mulugeta] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 275 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045615-7 PY 2006 BP 791 EP 816 PG 26 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA BCR99 UT WOS:000311229600032 ER PT J AU Montrose, MH Akiba, Y Takeuchi, K Kaunitz, JD AF Montrose, Marshall H. Akiba, Yasutada Takeuchi, Koji Kaunitz, Jonathan D. BE Johnson, LR TI Gastroduodenal Mucosal Defense SO PHYSIOLOGY OF THE GASTROINTESTINAL TRACT, VOLS 1 AND 2, 4TH EDITION LA English DT Article; Book Chapter ID DUODENAL BICARBONATE SECRETION; PROSTAGLANDIN-E-RECEPTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR; GASTRIC EPITHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; INTESTINAL TREFOIL FACTOR; NECTURUS ANTRAL MUCOSA; PANCREATIC-DUCT CELLS; GENE-RELATED PEPTIDE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS C1 [Montrose, Marshall H.] Univ Cincinnati, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA. [Akiba, Yasutada] W Los Angeles VAMC, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Takeuchi, Koji] Kyoto Pharmaceut Univ, Dept Pharmacol & Expt Therapeut, Yamashina Ku, Kyoto 607, Japan. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] W Los Angeles VAMC, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. RP Montrose, MH (reprint author), Univ Cincinnati, Dept Mol & Cellular Physiol, Med Sci Bldg,Room 4253,231 Albert Sabin Way, Cincinnati, OH 45267 USA. NR 425 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045615-7 PY 2006 BP 1259 EP 1291 PG 33 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA BCR99 UT WOS:000311229600052 ER PT J AU Montalbetti, N Dalghi, M Repetto, M Cantiello, HF AF Montalbetti, N Dalghi, M Repetto, M Cantiello, HF TI Role of oxidative stress in the control of the TRPP2 channel, polycystin-2 in the human syncytiotrophoblast SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales, RA-1113 Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A58 EP A58 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200207 ER PT J AU Montalbetti, N Cantero, MR Cantiello, HF AF Montalbetti, N Cantero, MR Cantiello, HF TI Contributionofthecyclicampsecondmessengerpathwaytothe control of cation channels in human syncytiotrophoblast SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A58 EP A58 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200208 ER PT J AU Montalbetti, N Li, Q Chen, XZ Cantiello, HF AF Montalbetti, N Li, Q Chen, XZ Cantiello, HF TI Cation channel function in the human syncytiotroproblast is under control of microtubular structures SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Univ Alberta, Dept Physiol, Edmonton, AB, Canada. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A58 EP A58 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200206 ER PT J AU Movassaghi, K Halen, IV Ganchi, P Amin-Hanjani, S Mesa, J Yaremchuk, MJ AF Movassaghi, K Halen, IV Ganchi, P Amin-Hanjani, S Mesa, J Yaremchuk, MJ TI Cranioplasty with subcutaneously preserved autologous bone grafts SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID DECOMPRESSIVE CRANIECTOMY; CEREBRAL INFARCTION; CRANIAL DEFECT; FLAPS; REPAIR; FROZEN; FRESH AB Background: The efficacy of reconstructing a cranial defect with the craniectomy bone graft (bone flap) banked in a subcutaneous pocket of the abdominal wall after emergency decompressive craniotomy was evaluated. Methods: A retrospective study was performed on 53 of 65 consecutive patients who, underwent emergency decompressive craniectomy and bone graft placement in the abdominal wall and survived to graft replacement. Clinical outcome after graft replacement was determined by the adequacy of the recovered craniectomy graft to achieve satisfactory reconstruction, the incidence of infection and the need for revisional surgery. Results: Forty-nine of the 53 patients (92 percent) in whom delayed autogenous graft replacement was attempted achieved a satisfactory one-stage reconstruction. In 42 of these 49 patients, autogenous graft replacement alone was per-formed. In eight patients it was necessary to supplement the graft with alloplastic material to achieve desired contour. One patient who underwent reconstruction with the autogenous bone graft alone, underwent late revision cranioplasty to improve contour. There were three infections. One graft was found infected in the abdominal pocket at retrieval. Two were lost to operative infection after graft replacement. Histology of two stored grafts performed after abdominal pocket retrieval demonstrated a mixture of necrotic and newly formed woven bone. A bone scan performed 1 year after graft replacement showed radionuclide activity of the graft almost identical to that of intact neighboring bone. Conclusions: Subcutaneous storage preserves viability of portions of autogenous bone grafts. Cranioplasty per-formed with a subcutaneously preserved craniectomy graft has a low revision rate. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Surg, Div Plast Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Surg, Div Plast Surg, Suite 453, Boston, MA 02114 USA. EM dr.y@dryaremchuk.com NR 22 TC 51 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2006 VL 117 IS 1 BP 202 EP 206 DI 10.1097/01.prs.0000187152.48402.17 PG 5 WC Surgery SC Surgery GA 000CX UT WOS:000234439600029 PM 16404268 ER PT B AU Huang, J Harrington, D AF Huang, J Harrington, D BE Nikulin, M Commenges, D Huber, C TI Operating characteristics of partial least squares in right-censored data analysis and its application in predicting the change of HIV-I RNA SO PROBABILITY, STATISTICS AND MODELLING IN PUBLIC HEALTH LA English DT Proceedings Paper CT Workshop on Probability, Statistics and Modelling in Public Health CY SEP 22-23, 2003 CL Bordeaux, FRANCE SP l IFR-99 Sante Publique DE dimension reduction; partial least squares; accelerative failure time model; cross-validation; prediction ID PRINCIPAL COMPONENTS REGRESSION; TYPE-1 PROTEASE INHIBITOR; LINEAR-REGRESSION; EFFECTS MODELS; SURVIVAL-DATA; RESISTANCE; SHRINKAGE; VARIABLES; ESTIMATORS; SAQUINAVIR AB It is often of interest to effectively use the information on a large number of covariates in predicting response or outcome. Various statistical tools have been developed to overcome the difficulties caused by the high-dimensionality of the covariate space in the setting of a linear regression model. This paper focuses on the situation where the outcomes of interest are subjected to right censoring. We implement the extended partial least squares method along with other commonly used approaches for analyzing the high dimensional covariates to a data set from AIDS clinical trials (ACTG333). Predictions were computed on the covariate effect and the response for a future subject with a set of covariates. Simulation studies were conducted to compare our proposed methods with other prediction procedures for different numbers of covariates, different correlations among the covariates and different failure time distributions. Mean squared prediction error and mean absolute distance were used to measure the accuracy of prediction on the covariate effect and the response, respectively. We also compared the prediction performance of different approaches using numerical studies. The results show that the Buckley-James based partial least squares, stepwise subset model selection and principal components regression have similar predictive power and the partial least squares method has several advantages in terms of interpretability and numerical computation. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr Suite 1102, Chicago, IL 60611 USA. Dana Farber Canc Inst, Harvard Sch Public Hlth, Dept Biostat Sci, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. RP Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr Suite 1102, Chicago, IL 60611 USA. EM jjhuang@northwestern.edu; dph@jimmy.harvard.edu FU AI58217 awarded by the National Institute of Allergy and Infectious Diseases [AI24643, AI58217]; NIH; Statistics and Data Analysis Center (SDAC) of the AIDS Clinical Trials Group (ACTG) FX This work was supported by the grants AI24643 and AI58217 awarded by the National Institute of Allergy and Infectious Diseases, NIH. The data set from protocol 333 was graciously provided by the Statistics and Data Analysis Center (SDAC) of the AIDS Clinical Trials Group (ACTG). NR 41 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26022-6 PY 2006 BP 202 EP + DI 10.1007/0-387-26023-4_14 PG 5 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Public, Environmental & Occupational Health; Mathematics GA BDG73 UT WOS:000233422800014 ER PT B AU Schmahmann, JD AF Schmahmann, J. D. GP Medimond TI The cerebellar cognitive affective syndrome and the dysmetria of thought theory: Clinical relevance for the developing brain SO Proceedings of the 10th International Child Neurology Congress LA English DT Proceedings Paper CT 10th International Child Neurology Congress CY JUN 11-16, 2006 CL Montreal, CANADA ID POSTERIOR-FOSSA TUMORS; DEFICIT HYPERACTIVITY DISORDER; CHILDREN; CHILDHOOD; RESECTION; DIFFICULTIES; ADOLESCENTS; HYPOPLASIA; SEQUELAE; LESIONS AB The cerebellum is involved not only in the coordination of movement, but also in the realms of cognition and emotion. This assertion is supported by anatomical and functional imaging studies, and behavioral observations in animals. The cerebellar cognitive affective syndrome (CCAS) that we described in adults with lesions confined to cerebellum, and in children surviving resection of cerebellar tumors anchored these observations in clinical neurology. The CCAS is characterized by impairments in executive function, visual spatial analysis, and selected aspects of language, with emotional dysregulation when lesions involve the cerebellar vermis. These findings are detected in children with complete or partial cerebellar agenesis, cerebellar hypoplasia with non-progressive cerebellar ataxia, and those born very preterm. Additionally, children with disorders that are defined by behavioral impairments including early infantile autism, dyslexia and attention deficit hyperactivity disorder also have a link to the cerebellum. Some adolescents develop an atypical psychosis some years after resection of cerebellar tumors in early childhood. C1 Massachusetts Gen Hosp, Ataxia Unit, Cognit Behav Neurol Unit, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Ataxia Unit, Cognit Behav Neurol Unit, Boston, MA 02114 USA. NR 43 TC 0 Z9 0 U1 0 U2 4 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-7587-248-1 PY 2006 BP 121 EP 129 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BFP06 UT WOS:000243530600021 ER PT B AU Yaremchuk, MJ Randolph, MA AF Yaremchuk, M. J. Randolph, M. A. BE Diner, PA Arnaud, E Vazquez, MP TI Cartilage tissue engineering SO Proceedings of the 5th International Congress of Maxillofacial and Craniofacial Distraction LA English DT Proceedings Paper CT 5th International Congress of the Maxillofacial and Craniofacial Distraction CY JUN 21-24, 2006 CL Paris, FRANCE ID CHONDROCYTES; COMPOSITE; TRANSPLANTATION; DEGRADATION; HYDROGELS; COLLAGEN; POLYMER; CELLS; BONE AB Tissues could be engineered using cells and polymer scaffolds. A viable cell source is crucial for generating extracellular matrix, and we have explored numerous possibilities including autologous chondrocytes from several anatomical sites, allogeneic chondrocytes, and stem cells. Each of these cell populations presents different opportunities and challenges for generating extracellular matrix and healing at the defect site. The second component for successfully engineering cartilage or bone is having a suitable delivery vehicle or scaffold, many of which have been described for bone and cartilage formation and repair. We have developed several hydrogel polymers that could be employed for cartilage or bone regeneration, some that can be chemically synthesized to meet specific requirements for tissue generation. Other strategies may include using both degradable and nondegradable scaffolds to achieve the desired results of tissue formation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yaremchuk, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-252-6 PY 2006 BP 5 EP 10 PG 6 WC Dentistry, Oral Surgery & Medicine; Orthopedics SC Dentistry, Oral Surgery & Medicine; Orthopedics GA BFP13 UT WOS:000243535300002 ER PT J AU Heist, EK Ruskin, JN AF Heist, EK Ruskin, JN TI Atrial fibrillation and congestive heart failure: Risk factors, mechanisms, and treatment SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID LEFT-VENTRICULAR DYSFUNCTION; CARDIAC RESYNCHRONIZATION THERAPY; ARRHYTHMIA SUPPRESSION TRIAL; RHYTHM MANAGEMENT AFFIRM; SINUS RHYTHM; SYSTOLIC DYSFUNCTION; CATHETER ABLATION; DILATED CARDIOMYOPATHY; RETROSPECTIVE ANALYSIS; MYOCARDIAL-INFARCTION C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 32 Fruit St,GRB 122, Boston, MA 02114 USA. EM jruskin@partners.org NR 85 TC 42 Z9 45 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JAN-FEB PY 2006 VL 48 IS 4 BP 256 EP 269 DI 10.1016/j.pcad.2005.09.001 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025SS UT WOS:000236287800004 PM 16517247 ER PT B AU Hespell, RB Paster, BJ Dewhirst, FE AF Hespell, Robert B. Paster, Bruce J. Dewhirst, Floyd E. BE Dworkin, M Falkow, S Rosenberg, E Schleifer, KH Stackebrandt, E TI The Genus Selenomonas SO PROKARYOTES: A HANDBOOK ON THE BIOLOGY OF BACTERIA, VOL 4, THIRD EDITION: BACTERIA: FIRMICUTES, CYANOBACTERIA LA English DT Article; Book Chapter ID ANAEROBIC RUMEN BACTERIA; NUTRITIONAL CHARACTERISTICS; SP-NOV; LACTATE-DEHYDROGENASE; CONTINUOUS CULTURE; BOVINE RUMEN; RUMINANTIUM; GROWTH; GLUCOSE; FERMENTATION C1 [Hespell, Robert B.] ARS, USDA, No Reg Res Ctr, Peoria, IL 61604 USA. [Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Dewhirst, Floyd E.] Forsyth Dent Ctr, Boston, MA 02115 USA. RP Hespell, RB (reprint author), ARS, USDA, No Reg Res Ctr, Peoria, IL 61604 USA. NR 52 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-25494-4 PY 2006 BP 982 EP 990 DI 10.1007/0-387-30744-3_33 D2 10.1007/0-387-30744-3 PG 9 WC Microbiology SC Microbiology GA BKJ68 UT WOS:000268326600033 ER PT S AU Marmar, CR McCaslin, SE Metzler, TJ Best, S Weiss, DS Fagan, J Liberman, A Pole, N Otte, C Yehuda, R Mohr, D Neylan, T AF Marmar, Charles R. McCaslin, Shannon E. Metzler, Thomas J. Best, Suzanne Weiss, Daniel S. Fagan, Jeffery Liberman, Akiva Pole, Nnamdi Otte, Christian Yehuda, Rachel Mohr, David Neylan, Thomas BE Yehuda, R TI Predictors of posttraumatic stress in police and other first responders SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE police; PTSD; risk; first responders; peritraumatic ID EMERGENCY SERVICES PERSONNEL; CRITICAL INCIDENT EXPOSURE; OF-LIFE OUTCOMES; VIETNAM VETERANS; ACOUSTIC STARTLE; PTSD SYMPTOMS; RISK-FACTORS; FOLLOW-UP; DISORDER; OFFICERS AB We provide an overview of previous research conducted by our group on risk and resilience factors for PTSD symptoms in police and other first responders. Based on our work, the findings of other investigators on individual differences in risk for PTSD, and drawing on preclinical studies fear conditioning and extinction, we propose a conceptual model for the development of PTSD symptoms emphasizing the role of vulnerability and resilience to peritraumatic panic reactions. We tested this conceptual model in a cross-sectional sample of police officers (n = 715). Utilizing an hierarchical linear regression model we were able to explain 39.7% of the variance in PTSD symptoms. Five variables remained significant in the final model; greater peritraumatic distress (beta = 0.240, P <.001), greater peritraumatic dissociation (beta = 0.174, P <.001), greater problem-solving coping (beta = 0.103, P <.01), greater routine work environment stress (beta = 0.182,P <.001), and lower levels of social support (beta = -0.246,P <.001). These results were largely consistent with the proposed conceptual model. Next steps in this line of research will be to test this model prospectively in a sample of 400 police academy recruits assessed during training and currently being followed for the first 2 years of police service. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. Columbia Univ, New York, NY 10027 USA. Natl Inst Justice, Washington, DC 20531 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Mt Sinai Sch Med, Div Traumat Stress Studies, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Marmar, CR (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St,116 P, San Francisco, CA 94121 USA. EM Charles.marmar@med.va.gov FU NIMH NIH HHS [R01-MH56350] NR 49 TC 95 Z9 96 U1 6 U2 31 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 1 EP 18 DI 10.1196/annals.1364.001 PG 18 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600001 PM 16891557 ER PT S AU Golier, JA Harvey, PD Legge, J Yehuda, R AF Golier, Julia A. Harvey, Philip D. Legge, Juliana Yehuda, Rachel BE Yehuda, R TI Memory performance in older trauma survivors - Implications for the longitudinal course of PTSD SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE trauma; memory; aging; neuropsychology; geriatric ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; INTIMATE PARTNER VIOLENCE; HIPPOCAMPAL VOLUME; COMBAT VETERANS; HOLOCAUST SURVIVORS; COGNITIVE DEFICITS; PYRAMIDAL NEURONS; VIETNAM VETERANS; EXPLICIT MEMORY AB Impaired declarative memory performance and smaller hippocampal volume have been observed in young and middle-aged adults with chronic posttraumatic stress disorder (PTSD). These alterations may put trauma survivors with PTSD at greater risk for cognitive decline in later life. This article focuses on the emerging literature on neuropsychological impairment in aging trauma survivors, in particular, elderly combat veterans and survivors of the Holocaust. In veterans and in Holocaust survivors, PTSD was associated with substantial impairments in learning, free and cued recall, and recognition memory compared to the respective nonexposed subjects; however, in neither group was PTSD associated with impaired retention or "rapid forgetting." Additionally, PTSD was not associated with smaller right or left hippocampal volume in either cohort. PTSD is associated with considerable cognitive burden with age. Longitudinal studies of older subjects are warranted to examine whether PTSD is associated with accelerated aging or progressive memory loss. C1 James J Peters VA Med Ctr, OOMH, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Golier, JA (reprint author), James J Peters VA Med Ctr, OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Julia.golier@med.va.gov NR 49 TC 35 Z9 35 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 54 EP 66 DI 10.1196/annals.1364.006 PG 13 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600006 PM 16891562 ER PT S AU Shin, LM Rauch, SL Pitman, RK AF Shin, Lisa M. Rauch, Scott L. Pitman, Roger K. BE Yehuda, R TI Amygdala, medial prefrontal cortex, and hippocampal function in PTSD SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE anterior cingulate; posttraumatic stress disorder; fMRI; PET; neuroimaging ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; EMOTIONAL FACIAL EXPRESSIONS; INTIMATE PARTNER VIOLENCE; ANTERIOR CINGULATE; SYMPTOM PROVOCATION AB The last decade of neuroimaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). Neuroimaging research reviewed in this article reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. Lastly, the reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD. Remaining research questions and related future directions are presented. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Medford, MA 02155 USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM lisa.shin@tufts.edu NR 98 TC 413 Z9 421 U1 12 U2 62 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 67 EP 79 DI 10.1196/annals.1364.007 PG 13 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600007 PM 16891563 ER PT S AU Yehuda, R AF Yehuda, Rachel BE Yehuda, R TI Advances in understanding neuroendocrine alterations in PTSD and their therapeutic implications SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE posttraumatic stress disorder; cortisol; neuroendocrine alterations; novel therapeutic strategies; hypothalamic-pituitary-adrenal axis ID POSTTRAUMATIC-STRESS-DISORDER; DEXAMETHASONE-SUPPRESSION TEST; CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; URINARY CORTISOL EXCRETION; PERIPHERAL MONONUCLEAR LEUKOCYTES; GLUCOCORTICOID-RECEPTOR RESPONSE; BORDERLINE PERSONALITY-DISORDER; MAJOR DEPRESSIVE DISORDER; VEHICLE ACCIDENT VICTIMS AB The findings from investigations of the neuroendocrinology of posttraumatic stress disorder (PTSD) have highlighted alterations that have not historically been associated with pathologic processes, and have, accordingly, raised several questions about the nature of the findings and their relationship to PTSD. The most infamous of these observations-low cortisol levels-has been the subject of much discussion and scrutiny because the finding has been both counterintuitive, and not uniformly reproducible. This fact notwithstanding, novel therapeutic approaches to the treatment of PTSD are in large part predicated on the assumption that glucocorticoid levels may be lower in PTSD. This article summarizes important neuroendocrine observations in cortisol and provides strategies for understanding what has emerged over the past two decades, to be a complex and sometimes contradictory literature. C1 Mt Sinai Sch Med, Div Traumat Stress Studies, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@med.va.gov; rachel.yehuda@med.va.gov FU NIMH NIH HHS [R01MH064675, R01MH249555] NR 144 TC 149 Z9 152 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 137 EP 166 DI 10.1196/annals.1364.012 PG 30 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600012 PM 16891568 ER PT S AU Pitman, RK Gilbertson, MW Gurvits, TV May, FS Lasko, NB Metzger, LJ Shenton, ME Yehuda, R Orr, SP AF Pitman, Roger K. Gilbertson, Mark W. Gurvits, Tamara V. May, Flavia S. Lasko, Natasha B. Metzger, Linda J. Shenton, Martha E. Yehuda, Rachel Orr, Scott P. CA Harvard VA PTSD Twin Study Investi BE Yehuda, R TI Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE stress disorders; posttraumatic; twins; monozygotic; startle response; neurological examination; magnetic resonance imaging; hippocampus; septum pellucidum ID POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL VOLUME; DAMAGE; MRI; VULNERABILITY; REGISTRY; NUCLEUS; BRAIN AB A biological abnormality found to be associated with posttraumatic stress disorder (PTSD) may be, among other things, a pretrauma vulnerability factor, that is, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD upon traumatic exposure. Alternately, it may be an acquired PTSD sign, that is, it may have developed after the traumatic exposure, along with the PTSD. We have studied pairs of Vietnam combat veterans and their noncombat-exposed, identical twins in an effort to resolve these competing origins. Combat veterans were diagnosed as current PTSD or non-PTSD (i.e., never had). Average heart rate responses (HRRs) to a series of sudden, loud-tone presentations were larger in Vietnam combat veteran twins with PTSD, but these larger responses were not shared by their noncombat-exposed cotwins, whose responses were similar to those of the non-PTSD combat veterans and their noncombat-exposed cotwins. These results suggest that larger HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast, increased neurological soft signs (NSSs), diminished hippocampal volume, and presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat veteran twins with PTSD and their "high-risk," unexposed cotwins compared to Vietnam combat veteran twins without PTSD and their "low-risk," unexposed cotwins. These results support the conclusion that the latter abnormalities represent antecedent, familial vulnerability factors for developing chronic PTSD upon exposure to a traumatic event. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. VA Med Ctr, Res Serv, Manchester, NH USA. Brigham & Womens Hosp, Neuroimaging Lab, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Surg Planning Lab, MRI Div, Dept Radiol, Boston, MA 02115 USA. James J Peters VA Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 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 [K02MH01110, R01 MH054636, K02 MH001110-10, R01MH54636, K02 MH001110] NR 30 TC 84 Z9 86 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 242 EP 254 DI 10.1196/annals.1364.019 PG 13 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600019 PM 16891575 ER PT S AU Yehuda, R Flory, JD Southwick, S Charney, DS AF Yehuda, Rachel Flory, Janine D. Southwick, Steven Charney, Dennis S. BE Yehuda, R TI Developing an agenda for translational studies of resilience and vulnerability following trauma exposure SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE resilience; PTSD; trauma; translational research; brain; neuroendocrine markers ID POSTTRAUMATIC-STRESS-DISORDER; PITUITARY-ADRENOCORTICAL REGULATION; CORTICOTROPIN-RELEASING FACTOR; NEUROPEPTIDE-Y CONCENTRATIONS; STAGE BREAST-CANCER; DEHYDROEPIANDROSTERONE-SULFATE; SOCIAL SUPPORT; DEXAMETHASONE SUPPRESSION; MAJOR DEPRESSION; URINARY CORTISOL AB Here we outline a translational research agenda for studies of resilience, defined as the process of adapting well in the face of adversity or trauma. We argue that an individual differences approach to the study of resilience, in which the full range of behavioral and biological responses to stress exposure is examined can be applied across human samples (e.g., people who have developed psychopathology versus those who have not; people who have been exposed to trauma versus those who have not) and even, in some cases, across species. We delineate important psychological resilience-related factors including positive affectivity and optimism, cognitive flexibility, coping, social support, emotion regulation, and mastery. Key brain regions associated with stress-related psychopathology have been identified with animal models of fear (e.g., extinction and fear conditioning; memory reconsolidation) and we describe how these regions can be studied in humans using neuroirnaging technology. Finally, we cite recent research identifying neuroendocrine markers of resilience and recovery in humans (e.g., neuropeptide Y [NPY], dehydroepiandrosterone [DHEA]) that can also be measured, in some cases, in other species. That exposure to adversity or trauma does not necessarily lead to impairment and the development of psychopathology in all people is an important observation. Understanding why this is so will provide clues for the development of therapeutic interventions for those people who do develop stress-related psychopathology, or even for the prevention of adverse outcomes. C1 Mt Sinai Sch Med, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. Vet Affairs Connecticut, New Haven, CT 06510 USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov; Rachel.Yehuda@med.va.gov NR 94 TC 112 Z9 114 U1 3 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 379 EP 396 DI 10.1196/annals.1364.028 PG 18 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600028 PM 16891584 ER PT S AU Tischler, L Brand, SR Stavitsky, K Labinsky, E Newmark, R Grossman, R Buchsbaum, MS Yehuda, R AF Tischler, Lisa Brand, Sarah R. Stavitsky, Karina Labinsky, Ellen Newmark, Randall Grossman, Robert Buchsbaum, Monte S. Yehuda, Rachel BE Yehuda, R TI The relationship between hippocampal volume and declarative memory in a population of combat veterans with and without PTSD SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE post-traumatic stress disorder; memory; trauma exposure; hippocampal volume; CVLT ID POSTTRAUMATIC-STRESS-DISORDER AB Both reduced hippocampal volume and cognitive alterations have been found in posttraumatic stress disorder (PTSD). The purpose of this article was to examine the relationship between hippocampal volume, combat exposure, symptom severity, and memory performance in a sample of combat veterans with and without a history of PTSD. Subjects were 33 male veteran volunteers (16 PTSD+, 17 PTSD-) who underwent an MRI and neuropsychological testing with the California Verbal Learning Test (CVLT), a measure of declarative memory. Relationships between hippocampal volume (i.e., right + left hippocampal volume/whole brain volume) and performance on the CVLT were determined using partial correlational analysis controlled for age and Wechsler Adult Intelligence Scale, Third Edition (WAIS-III) vocabulary scores. Percent hippocampal volume for the entire sample was positively associated with several aspects of memory performance as reflected by the CVLT. In the PTSD+ group, CVLT performance was negatively correlated with lifetime, but not current CAPS symptoms. CVLT performance appears to be strongly correlated with hippocampal volume in a group of trauma survivors with and without PTSD. Insofar as CVLT performance in the PTSD group was negatively associated with worst episode, but not to current PTSD symptoms, memory performance in combat veterans may reflect some aspect of risk related to the magnitude of the psychological response to trauma, rather than current symptoms that may be interfering with cognitive performance. It will be of interest to study cognitive abilities that may relate to the likelihood of specific PTSD symptoms and to track changes in CVLT performance and hippocampal volume over time in persons with and without a history of trauma exposure. C1 James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov; Rachel.Yehuda@med.va.gov NR 17 TC 34 Z9 37 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 405 EP 409 DI 10.1196/annals.1364.031 PG 5 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600031 PM 16891587 ER PT S AU Grossman, R Yehuda, R Golier, J McEwen, B Harvey, P Maria, NS AF Grossman, Robert Yehuda, Rachel Golier, Julia McEwen, Bruce Harvey, Philip Maria, Nelly Sta. BE Yehuda, R TI Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad & Sci DE posttraumatic stress disorder; cortisol; cognitive function; working memory; declarative memory; attention; hypothalamicpituitary-adrenal axis ID POSTTRAUMATIC-STRESS-DISORDER; GLUCOCORTICOID-RECEPTOR NUMBER; URINARY CORTISOL EXCRETION; LONG-TERM POTENTIATION; CA3 PYRAMIDAL NEURONS; HIPPOCAMPAL VOLUME; DECLARATIVE MEMORY; PLASMA-CORTISOL; COMBAT VETERANS; WORKING-MEMORY AB On the basis of peripheral (nonbrain) neuroendocrine findings in subjects with posttraumatic stress disorder (PTSD), it has been hypothesized that these individuals also have a greater central (brain) sensitivity to glucocorticoids. In nonpsychiatric subjects, it has been found that working and declarative memory performance is selectively impaired by acute glucocorticoid administration. We hypothesized that subjects with PTSD, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration. These data are part of a larger study using functional neuroimaging and peripheral HPA axis measures in these same subjects. Subjects underwent a 0.5-mg dexamethasone suppression test and measurement of basal cortisol, basal plasma lymphocyte glucocorticoid receptor number, and postdexamethasone cortisol on a separate day. Under double-blind randomized crossover conditions, 17-mg hydrocortisone or placebo was administered by intravenous (i.v.) bolus to 15 medication-free PTSD subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by age, sex, and education level. Participants then underwent positron emission tomography (PET) scanning and 90 min after the initial drug/placebo administration, cognitive testing was then performed. By repeated measures ANCOVA (covaried for baseline performance on that neuropsychological test), neither attention tasks of digit span forward nor backward showed significant change. However, there were significant drug (F = 17.644, df = 1,25 P < 0.001), group (F = 4.383, df 1,25 P = 0.048), and drug by group interactions (F = 4.756, df 1,25 P = 0.040) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The subject group with PTSD experienced a greater decline in verbal declarative memory performance following hydrocortisone administration. For working memory, there were significant group (F = 6.048, df = 1,25 P = 0.022) and drug by group interactions (F = 6.048, df = 1,25 P = 0.022) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The hydrocortisone administration led to impairment in working memory in the group of subjects with PTSD, but not in the control subject group. Exploratory correlations between percent cortisol suppression following dexamethasone and baseline plasma lymphocyte glucocorticoid receptor number with declarative and working memory measures among subject groups separately and in a combined way revealed a negative correlation between lymphocyte glucocorticoid receptor density and working memory (r = -0.54, df = 25, P = 0.008). Brain sensitivity to glucocorticoids appears to be greater in subjects with PTSD. Heightened vulnerability of declarative memory in subjects with PTSD may indicate hippocampal involvement, whereas working memory vulnerability suggests additional brain regions (prefrontal, cingulate, temporal, and parietal cortices) and neurotransmitter systems (dopamine and serotonin) particularly sensitive to glucocorticoids in persons with PTSD. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Rockefeller Res Inst, Dept Neuroendocrinol, New York, NY USA. Univ Pittsburgh, Med Ctr, Dept Psychol, Pittsburgh, PA USA. RP Grossman, R (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230, New York, NY 10029 USA. EM robertgrossman@yahoo.com FU NCRR NIH HHS [5M01RR0071]; NIMH NIH HHS [1K08MH01543-01A1, R01MH49555] NR 42 TC 30 Z9 30 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 410 EP 421 DI 10.1196/annals.1364.032 PG 12 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600032 PM 16891588 ER PT S AU McCaslin, SE Inslicht, SS Neylan, TC Metzler, TJ Otte, C Lenoci, M Henn-Haase, C Best, S Yehuda, R Marmar, CR AF McCaslin, Shannon E. Inslicht, Sabra S. Neylan, Thomas C. Metzler, Thomas J. Otte, Christian Lenoci, Maryann Henn-Haase, Clare Best, Suzanne Yehuda, Rachel Marmar, Charles R. BE Yehuda, R TI Association between alexithymia and neuroendocrine response to psychological stress in police academy recruits SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE alexithymia; neuroendocrine; stress; posttraumatic stress disorder ID SCALE AB Alexithymia has been associated with both posttraumatic stress disorder and neuroendocrine responses to stress. This study examined the relationship of alexithymia to salivary cortisol and 3-methoxy4-hydroxy-phenylglycol (MHPG) in a sample of police academy recruits exposed to a video stress challenge. Alexithymia scores were negatively associated with catecholamine response to the video challenge but no association was found between alexithymia scores and cortisol reactivity. C1 Univ Calif San Francisco, PTSD Res Program, VAMC, San Francisco, CA 94121 USA. Dept Psychiat, San Francisco, CA 94121 USA. Univ Hosp Hamburg Eppendorf, D-20246 Hamburg, Germany. Mt Sinai Sch Med, Div Traumat Stress Studies, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP McCaslin, SE (reprint author), Univ Calif San Francisco, PTSD Res Program, VAMC, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM Shannon.McCaslin@va.gov NR 7 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 425 EP 427 DI 10.1196/annals.1364.034 PG 3 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600034 PM 16891590 ER PT S AU Inslicht, SS Marmar, CR Neylan, TC Metzler, TJ Hart, SL Otte, C McCaslin, SE Larkin, GL Hyman, KB Baum, A AF Inslicht, Sabra S. Marmar, Charles R. Neylan, Thomas C. Metzler, Thomas J. Hart, Stacey L. Otte, Christian McCaslin, Shannon E. Larkin, Gregory Luke Hyman, Kelly B. Baum, Andrew BE Yehuda, R TI Increased cortisol in women with intimate partner violence-related posttraumatic stress disorder SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE posttraumatic stress disorder; cortisol; HPA axis; platelet catecholamines; epinephrine; norepinephrine; intimate partner violence ID VICTIMS AB Intimate partner violence (IPV) is a chronic and recurrent traumatic stressor associated with PTSD; however, its biological correlates are not well understood. This study examined diurnal salivary cortisol and platelet catecholamines in women with lifetime IPV-related PTSD and in women exposed to IPV who did not develop PTSD. Cortisol was elevated in women with lifetime PTSD compared to controls. No differences were found for platelet catecholamines. C1 Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. Univ Hosp Hamburg Eppendorf, D-20246 Hamburg, Germany. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RP Inslicht, SS (reprint author), Vet Affairs Med Ctr, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM Sabra.Inslicht@med.va.gov RI Hart, Stacey/E-4819-2011; OI LARKIN, GREGORY LUKE/0000-0002-8655-7824 NR 6 TC 22 Z9 22 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 428 EP 429 DI 10.1196/annals.1364.035 PG 2 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600035 PM 16891591 ER PT S AU Golier, JA Legge, J Yehuda, R AF Golier, Julia A. Legge, Juliana Yehuda, Rachel BE Yehuda, R TI The ACTH response to dexamethasone in Persian Gulf War veterans SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE PTSD; Gulf War; medically unexplained illness; ACTH; cortisol; dexamethasone ID POSTTRAUMATIC-STRESS-DISORDER; PITUITARY-ADRENAL AXIS; PHYSICAL HEALTH; PLASMA-CORTISOL; SUPPRESSION; SURVIVORS; ABUSE; PTSD; EXPOSURE; ILLNESS AB The basis of postdeployment health symptoms in Gulf War veterans remains poorly understood. Alterations in the feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis have been demonstrated in posttraumatic stress disorder (PTSD) and other bodily disorders related to stress. The objective of this article was to examine whether similar HPA axis alterations are related to Gulf War deployment, postdeployment health symptoms, or PTSD. Plasma adrenocorticotropic hormone (ACTH) was measured on consecutive mornings at 08:00 h before and after a low dose of oral dexamethasone (DEX) at 23:00 h in Gulf War veterans with PTSD (n = 14), Gulf War veterans without PTSD (n = 11), and healthy veterans never deployed to a war zone (n = 12). Both Gulf War veterans with PTSD and Gulf War veterans without PTSD had significantly lower post-DEX ACTH levels than the nonexposed veterans, in the absence of group differences in basal ACTH or DEX levels. Among Gulf War veterans, post-DEX ACTH levels were significantly associated with musculoskeletal symptoms. Gulf War deployment and postdeployment health symptoms appear to be associated with alterations in feedback regulation of the pituitary gland that suggests a possible common link between postdeployment health symptoms and other chronic stress-related conditions. C1 James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Golier, JA (reprint author), Bronx Vet Adm Med Ctr, COMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Julia.golier@med.va.gov NR 25 TC 9 Z9 9 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 448 EP 453 DI 10.1196/annals.1364.040 PG 6 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600040 PM 16891596 ER PT S AU Brand, SR Engel, SM Canfield, RL Yehuda, R AF Brand, Sarah R. Engel, Stephanie M. Canfield, Richard L. Yehuda, Rachel BE Yehuda, R TI The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE maternal PTSD; infant behavior; 9/11; cortisol ID POSTTRAUMATIC-STRESS-DISORDER; CORTISOL AB In view of evidence of in utero glucocorticoid programming, and our prior observation of lower cortisol levels in 9-month-old infants of mothers with posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we undertook an examination of the effect of in utero maternal stress, as determined by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in the infant. Methods: Ninety-eight pregnant women directly exposed to the World Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and completed a PTSD symptom questionnaire and a behavior rating scale to measure infant temperament, including distress to limitations, and response to novelty. Results: Mothers who developed PTSD in response to 9/11 had lower morning and evening salivary cortisol levels, compared to mothers who did not develop PTSD. Maternal morning cortisol levels were inversely related to their rating of infant distress and response to novelty (i.e., loud noises, new foods, unfamiliar people). Also, mothers who had PTSD rated their infants as having greater distress to novelty than did mothers without PTSD (t = 2.77, df = 61, P = 0.007). Conclusion: Longitudinal studies are needed to determine how the association between maternal PTSD symptoms and cortisol levels and infant temperament reflect genetic and/or epigenetic mechanisms of intergenerational transmission. C1 James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov; Rachel.Yehuda@med.va.gov FU NIEHS NIH HHS [P42 ES07384]; NIMH NIH HHS [R01 MH64675-01, 5R01 MH64675-03] NR 7 TC 48 Z9 55 U1 1 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 454 EP 458 DI 10.1196/annals.1364.041 PG 5 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600041 PM 16891597 ER PT S AU Labinsky, E Blair, W Yehuda, R AF Labinsky, Ellen Blair, William Yehuda, Rachel BE Yehuda, R TI Longitudinal assessment of dissociation in holocaust survivors with and without PTSD and nonexposed aged Jewish adults SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE PTSD; dissociation; holocaust; aging; longitudinal ID SCALE; RELIABILITY; VALIDITY AB The trajectory of posttraumatic stress disorder (PTSD) and PTSD-related symptoms in relation to aging is not well understood. We previously observed higher levels of dissociation as measured by the Dissociative Experiences Scale (DES) among older Holocaust survivors with, compared to those without, PTSD, though scores on the DES in Holocaust survivors were markedly lower than those that had been reported for younger cohorts. We undertook a longitudinal evaluation of dissociation in Holocaust survivors. Twenty-six Holocaust survivors with current PTSD, 30 Holocaust survivors without current PTSD, and 19 nonexposed were evaluated at the initial evaluation and subsequently 8.11 years later. Repeated measures analysis of variance (ANOVA) on the DES scores from these times demonstrated a significant main effect for time and a significant group by time interaction, reflecting a marked decline in Holocaust survivors, particularly those with PTSD. Controlling for age obliterated the effect of time, but not the group by time interaction. A similar pattern was shown with The Clinician Administered PTSD Scale (CAPS) scores. Different symptoms related to PTSD show different trajectories of change with age, with dissociation appearing to be less prominent with age. C1 Mt Sinai Sch Med, New York, NY 10029 USA. James J Peterson Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Labinsky, E (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1228, New York, NY 10029 USA. EM Ellen.Labinsky@msnyuhealth.org FU NCRR NIH HHS [M01 RR00071]; NIMH NIH HHS [R01 MH64675-01] NR 5 TC 12 Z9 12 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 459 EP 462 DI 10.1196/annals.1364.042 PG 4 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600042 PM 16891598 ER PT S AU Yehuda, R Labinsky, E Tischler, L Brand, SR Lavin, Y Blair, W Bierer, LM Goodman, RZ Grossman, RA AF Yehuda, Rachel Labinsky, Ellen Tischler, Lisa Brand, Sarah R. Lavin, Yonit Blair, William Bierer, Linda M. Goodman, Rachel Z. Grossman, Robert A. BE Yehuda, R TI Are adult offspring reliable informants about parental PTSD? A validation study SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE parental PTSD; Holocaust; offspring AB We developed a short questionnaire-Parental PTSD Questionnaire-(PPQ), designed to assess the presence of posttraumatic stress disorder (PTSD) symptoms in parents. Fifty-eight adult offspring of Holocaust survivors (23 men and 35 women) completed the questionnaire about a parent who was independently evaluated by a trained clinician using the Clinician Administered PTSD Scale (CAPS). Only 5.2% of the offspring reported, "not knowing" if their parent had experienced 10 or fewer symptoms, while 56.9% provided estimates for all 17 items. There were no significant differences between lifetime frequencies of the individual symptoms as endorsed on the PPQ compared to the CAPS when subjects with completed PPQs were compared with CAPS. Interrater reliability between offspring and clinician was highly significant for each of the items when evaluated separately so as to include data for subjects who endorsed not knowing if a certain symptom had been present. Further studies are warranted to examine the psychometric properties of this measure. C1 James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov; Rachel.Yehuda@med.va.gov NR 1 TC 13 Z9 14 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 484 EP 487 DI 10.1196/annals.1364.047 PG 4 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600047 PM 16891603 ER PT S AU Bierer, LM Tischler, L Labinsky, E Cahill, S Foa, E Yehuda, R AF Bierer, Linda M. Tischler, Lisa Labinsky, Ellen Cahill, Shawn Foa, Edna Yehuda, Rachel BE Yehuda, R TI Clinical correlates of 24-h cortisol and norepinephrine excretion among subjects seeking treatment following the World Trade Center attacks on 9/11 SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE 24-h cortisol; norepinephrine; 9/11; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; DEPRESSION; SEVERITY AB Whereas trauma-associated arousal has been linked fairly consistently with elevations in both glucocorticoids and catecholamines, neuroendocrine correlates of hyperarousal in the context of posttraumatic stress disorder (PTSD) have been more variable. Further, neuroendocrine predictors of the development of PTSD following trauma have been related to prior exposure, and data from several laboratories suggests that hyperarousal may develop in a neuroendocrine milieu of relatively diminished basal glucocorticoid secretion. Methods: In this article we examined 24-h cortisol and norepinephrine excretion in 42 treatment-seeking survivors of the 9/11 World Trade Center (WTC) attacks, 32 of whom met criteria for PTSD, and 15 of whom met criteria for major depression, at the time of evaluation; 14 of the 15 subjects meeting criteria for major depression also suffered from PTSD. Results: PTSD subjects' 24-h cortisol excretion (46.3 +/- 20.0 mu L/dL) was lower than that of the non-PTSD cohort (72.2 +/- 22.4 mu L/dL; t = 3.18, df = 37, P = 0.003), and 24-h urinary cortisol was negatively correlated with the experience of the WTC attacks as a Criterion-A event (r = -0.427, P = 0.007), and with self-rated avoidance (r = -0.466, P = 0.003) and total score (r = -0.398, P = 0.012) on the PTSD Symptom Scale (PSS). In contrast, 24-h norepinephrine excretion was not associated with the development of PTSD or with PTSD-related symptoms, but was negatively correlated with days since 9/11 at the time of evaluation (r = -0.393, P = 0.015). Discussion: The latter finding suggests a relationship of norepinephrine to a dimension of stress-related arousal not captured by the symptom-rating scales chosen for this study to reflect symptoms related to PTSD and other neuropsychiatric disorders, but instead, of one to that of the sudden multidimensional life disruption suffered by the WTC C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Yehuda, R (reprint author), Bronx Vet Adm Med Ctr, Bronx, NY USA. EM rachel.yehuda@med.va.gov; rachel.yehuda@med.va.gov NR 8 TC 24 Z9 24 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 514 EP 520 DI 10.1196/annals.1364.055 PG 7 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600054 PM 16891610 ER PT J AU Keel, PK Heatherton, TF Dorer, DJ Joiner, TE Zalta, AK AF Keel, PK Heatherton, TF Dorer, DJ Joiner, TE Zalta, AK TI Point prevalence of bulimia nervosa in 1982, 1992, and 2002 SO PSYCHOLOGICAL MEDICINE LA English DT Article ID EATING DISORDER INVENTORY; COLLEGE-STUDENTS; SOCIOECONOMIC-STATUS; SPECIFICITY; WEIGHT; TRENDS AB Background. Recent epidemiological data suggest a decline in bulimia nervosa (BN) incidence in primary care. We sought to examine BN point prevalence from 1982 to 2002 in a college population. Method. In 1982, 1992, and 2002, 800 women and 400 men were randomly sampled from a university for a study of health and eating patterns. Participation rates were 72% in women and 63% in men, resulting in n = 2491 participants. Results. BN point prevalence decreased significantly in women over the period of observation. Eating Disorder Inventory Bulimia scores decreased across cohorts, and these decreases remained significant when male and female and Caucasian and non-Caucasian students were analyzed separately. Conclusion. These data support a decline in BN rates that cannot be attributed to changes in service utilization. Changing socio-cultural factors may explain a true decrease in BN incidence and prevalence. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Keel, PK (reprint author), E11 Seashore Hall, Iowa City, IA 52242 USA. EM pamela-keel@uiowa.edu RI Heatherton, Todd/H-5478-2011; OI Zalta, Alyson/0000-0002-5159-8431 FU NIMH NIH HHS [R01 MH063758]; PHS HHS [R01-63758] NR 30 TC 81 Z9 82 U1 3 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2006 VL 36 IS 1 BP 119 EP 127 DI 10.1017/S0033291705006148 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 001WP UT WOS:000234573700014 PM 16202192 ER PT J AU Bogdan, R Perlis, RA Pizzagalli, DA AF Bogdan, Ryan Perlis, Roy A. Pizzagalli, Diego A. TI The effects of 5-HTT genotype and stress on hedonic capacity SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE stress; reward; depression C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S25 EP S25 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400113 ER PT J AU Ganis, G Schendan, HE Kosslyn, SM AF Ganis, Giorgio Schendan, Haline E. Kosslyn, Stephen M. TI Neuroimaging evidence for object model verification theory: Role of prefrontal control in visual object categorization SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE object categorization; functional neuroimaging; top-down processing C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 USA. Boston Univ, 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S40 EP S40 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400186 ER PT J AU Putnam, KM Kinreich, S Warfield, GA McSweeney, LB Zanarini, MC Rauch, SL Kim, DS Roenen, I Sharma, H AF Putnam, Katherine M. Kinreich, Sivan Warfield, Garrett A. McSweeney, Lauren B. Zanarini, Mary C. Rauch, Scott L. Kim, Dae-Shik Roenen, Itamar Sharma, Harish TI Automatic processes of the regulation of negative affect in borderline personality disorder: An event-related fMRI study SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE borderline personality disorder; emotion regulation; functional neuroimaging C1 Boston VAMC, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S80 EP S80 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400368 ER PT J AU Fava, M Rush, AJ AF Fava, M Rush, AJ TI Current status of augmentation and combination treatments for major depressive disorder: A literature review and a proposal for a novel approach to improve practice SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Review DE augmentation therapy; combination therapy; antidepressant-resistant depression; remission ID SEROTONIN REUPTAKE INHIBITORS; TREATMENT-RESISTANT DEPRESSION; PLACEBO-CONTROLLED TRIAL; TREATMENT-REFRACTORY DEPRESSION; ATYPICAL ANTIPSYCHOTIC-DRUGS; ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; BIPOLAR-II DEPRESSION; ADENOSYL-L-METHIONINE; STAR-ASTERISK-D AB Most patients with major depressive disorder (MDD) do not reach symptom remission. These patients with residual symptoms have worse function and worse prognosis than those who remit. Several augmentation and combination treatments are used to either increase the chances of achieving remission or to eliminate/minimize residual depressive symptoms. Evidence for these pharmacological approaches rests primarily on open, uncontrolled studies, and there are clearly not enough controlled studies. Clinicians should carefully weigh these different treatment options to increase their patients' chances of achieving and sustaining remission from depression. This paper will review the pertinent studies and will propose a novel approach to improve practice involving the use of augmentation or combination strategies at the outset of initial treatment to primarily enhance the chances of remission through synergy and/or a broader spectrum of action. This novel approach could potentially enhance retention and/or increase remission rates since the lack of response with antidepressant monotherapy may lead many depressed patients with little or no benefit to drop out of treatment, precluding the subsequent use of augmentation or combination strategies altogether. In addition, the emergence of certain side-effects (e.g., agitation, insomnia) or the persistence of some initial baseline symptoms (e.g., anxiety, insomnia) may lead to premature discontinuation from monotherapy in the absence of concomitant use of augmenting pharmacological options targeting these symptoms. C1 Harvard Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Texas, SW Med Sch, Dallas, TX 75235 USA. RP Fava, M (reprint author), Harvard Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, Sch Med, Bulfinch 351-55 Fruit St, Boston, MA 02114 USA. EM MFava@partners.org OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003, GMO N01 MH90003] NR 168 TC 97 Z9 99 U1 4 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 EI 1423-0348 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2006 VL 75 IS 3 BP 139 EP 153 DI 10.1159/000091771 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 035SI UT WOS:000237021600002 PM 16636629 ER PT J AU Rubin, GD Bradley, WG Foley, D Herold, CJ Jaramillo, D Seeger, LL AF Rubin, Geoffrey D. Bradley, William G., Jr. Foley, Dennis Herold, Christian J. Jaramillo, Diego Seeger, Leanne L. TI Image Interpretation Session: 2005 SO RADIOGRAPHICS LA English DT Editorial Material C1 Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Radiol, Milwaukee, WI 53226 USA. Univ Hosp Vienna, Dept Radiol, Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. David Geffen Sch Med, Los Angeles, CA USA. RP Rubin, GD (reprint author), Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. RI Rubin, Geoff/D-2557-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2006 VL 26 IS 1 BP 127 EP 127 DI 10.1148/rg.265055962 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 064GV UT WOS:000239078100013 ER PT J AU Mullins, ME AF Mullins, ME TI Modern emergent stroke imaging: Pearls, protocols, and pitfalls SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE ISCHEMIC-STROKE; PERFUSION COMPUTED-TOMOGRAPHY; TISSUE-PLASMINOGEN ACTIVATOR; ACUTE HEMISPHERIC STROKE; DIFFUSION-WEIGHTED MRI; CEREBRAL-ARTERY STROKE; EARLY CT SIGNS; HYPERACUTE STROKE; INTRAARTERIAL THROMBOLYSIS; CEREBROVASCULAR-DISEASE AB Stroke remains one of the most important clinical diagnoses for which patients are referred to the radiologist for emergent imaging. Timely and accurate imaging guides admission from the emergency department or transfer to a hospital with a dedicated stroke service, triage to the intensive care unit, anticoagulation, thrombolysis, and many other forms of treatment and management. It is important to approach each patient's imaging needs logically and tailor each work-up, and constantly to review the entire process for potential improvements. Time saved in getting an accurate diagnosis of stroke may indeed decrease morbidity and mortality. This article discusses the current management of stroke imaging and reviews the relevant literature. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Mullins, ME (reprint author), Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM Mark.Mullins@emoryheaIthcare.org NR 77 TC 10 Z9 10 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2006 VL 44 IS 1 BP 41 EP + DI 10.1016/j.rcl.2005.08.002 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 997DS UT WOS:000234225800004 PM 16297681 ER PT J AU Grant, PE Yu, D AF Grant, PE Yu, D TI Acute injury to the immature brain with hypoxia with or without hypoperfusion SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; PROTON MR SPECTROSCOPY; PERINATAL ASPHYXIA; ISCHEMIC INJURY; ENCEPHALOPATHY; STROKE; INFANT; DAMAGE AB This article reviews the imaging features and evolution of immature brain injury caused by hypoxia with or without hypoperfusion in the neonate and young child. Clinical presentations and available literature on mechanisms and clinical outcomes are discussed. In many of these cases, diffusion-weighted imaging does not show the full extent of the injury but detects a pattern of injury that is important in guiding clinical care. Awareness of the delayed cell death mechanisms is essential to understand diffusion-weighted imaging sensitivity and evolution and to provide the most accurate clinical interpretation, especially in cases of hypoxia with or without hypoperfusion. C1 Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. Shields MRI Hlth Care Grp, Brockton, MA USA. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, Ellison 237, Boston, MA 02114 USA. EM egrant2@partners.org FU NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [K23 NS42758] NR 34 TC 14 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2006 VL 44 IS 1 BP 63 EP + DI 10.1016/j.rcl.2005.08.001 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 997DS UT WOS:000234225800005 PM 16297682 ER PT S AU Bernards, A AF Bernards, Andre BE Balch, WE Der, CJ Hall, A TI Ras superfamily and interacting proteins database SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; REGULATOR RCC1; IDENTIFICATION AB For geneticists and other researchers alike it is often useful to know how many related proteins might perform similar functions. With this in mind, a survey was performed to determine what proportion of human and Drosophila genes code for Ras superfamily members and their positive or negative regulators. Results indicate that just < 2% of genes in both genomes predict such proteins. A database was compiled to provide easy access to this information. This database also includes information on approximately 360 putative Ras superfamily effector proteins and may be a useful tool for those interested in GTPase biology. C1 Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA USA. NR 17 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 1 EP 9 DI 10.1016/S0076-6879(05)07001-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800001 PM 16757309 ER PT S AU Avruch, J Praskova, M Ortiz-Vega, S Liu, MR Zhang, XF AF Avruch, Joseph Praskova, Maria Ortiz-Vega, Sara Liu, Mat-Rhew Zhang, Xian-Feng BE Balch, WE Der, CJ Hall, A TI Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID TUMOR-SUPPRESSOR RASSF1A; DOMAIN FAMILY PROTEIN; PROMOTES APOPTOSIS; EPIGENETIC INACTIVATION; EFFECTOR MOLECULE; BINDING-PROTEIN; LUNG-CANCER; CYCLE EXIT; K-RAS; DROSOPHILA AB The six human Nore1/RASSF genes encode a family of putative tumor suppressor proteins, each expressed as multiple mRNA splice variants. The predominant isoforms of these noncatalytic polypeptides are characterized by the presence in their carboxyterminal segments of a Ras-Association (RA) domain followed by a SARAH domain. The expression of the RASSF1A and Nore1A isoforms is extinguished selectively by gene loss and/or epigenetic mechanisms in a considerable fraction of epithelial cancers and cell lines derived there from, and reexpression usually suppresses the proliferation and tumorigenicity of these cells. RASSF1A/Nore1A can cause cell cycle delay in G1 and/or M and may promote apoptosis. The founding member, Nore1A, binds preferentially through its RA domain to the GTP-charged forms of Ras, Rap-1., and several other Ras subfamily GTPases with high affinity. By contrast, RASSF1, despite an RA domain 50% identical to Nore1, exhibits relatively low affinity for Ras-like GTPases but may associate with Ras-GTP indirectly. Each of the RASSF polypeptides, including the C elegans ortholog encoded by T24F1.3, binds to the Ste20-related protein kinases MST1 and MST2 through the SARAH domains of each partner. The recombinant MST1/2 kinases, spontaneous dimers, autoactivate in vitro through an intradimer transphosphorylation of the activation loop, and the Nore1/RASSF1 polypeptides inhibit this process. Recombinant MST1 is strongly activated in vivo by recruitment to the membrane; the recombinant MST1 that is bound to RasG12V through Nore1A is activated; however, the bulk of MST1 is not. Endogenous complexes of MST1. with both Nore1A and RASSF1A are detectable, and Nore1A/MST1 can associate with endogenous Ras in response to serum addition. Nevertheless, the physiological functions of the Nore1/RASSF polypeptides in mammalian cells, as well as the role of the MST1/2 kinases in their growth-suppressive actions, remain to be established. The Drosophila MST1/2 ortholog hippo is a negative regulator of cell cycle progression and is necessary for developmental apoptosis. Overexpression of mammalian MST1 or MST2 promotes apoptosis, as does overexpression of mutant active Ki-Ras. Interference with the ability of endogenous MST1/2 to associate with the Nore1/RASSF polypeptides inhibits Ras-induced apoptosis. At present, however, the relevance of KiRas-induced apoptosis to the physiological functions of c-Ras and to the growth-regulating actions of spontaneously occurring oncogenic Ras mutants is not known. C1 Massachusetts Gen Hosp, Dept Biol Mol, Diabet Unit, Boston, MA 02115 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Diabet Unit, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK17776, T32 DK007028]; NIGMS NIH HHS [GM51281] NR 63 TC 26 Z9 28 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 290 EP 310 DI 10.1016/S0076-6879(05)07025-4 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800025 PM 16757333 ER PT S AU Lafuente, E Boussiotis, VA AF Lafuente, Esther Boussiotis, Vassiliki A. BE Balch, WE Der, CJ Hall, A TI Rap 1 regulation of RIAM and cell adhesion SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID GTPASE RAP1; ACTIVATION; RAS; LYMPHOCYTES; AFFINITY; DISTINCT AB The small GTPase Rap1 has been involved in different cellular processes. Rap1 is known to increase cell adhesion by means of integrin activation, to induce cell spreading, and to regulate adherent junctions at cell-cell contacts. How Rap1 mediates these cell responses is poorly known, but currently developing evidence points to the involvement of different effector pathways. Recently, we described RIAM, a Rap1 interacting adaptor protein that regulates integrin activation and hence cell adhesion. RIAM is required for Rap1-induced adhesion and seems to control Rap1 localization at the plasma membrane, where Rap1 regulates integrin activation. In this chapter, we focus in the role of RIAM in regulating Rap1-mediated cell adhesion. We describe the method for studying the Rap1-RIAM interaction using in vitro and in vivo approaches such as yeast two hybrids, pull-down assays. and coimmunoprecipitation. The role of Rap1 and RIAM in integrin-mediated adhesion is studied by cell adhesion assays to immobilized integrin substrates and by changes in integrin activation as determined by activation epitope exposure. Finally, we describe an approach to determine the role of RIAM in regulating intracellular localization of active Rap1. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Lafuente, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 345 EP + DI 10.1016/S0076-6879(05)07029-1 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800029 PM 16757337 ER PT S AU Vasudevan, KM Ranganathan, P Rangnekar, VM AF Vasudevan, Krishna Murthi Ranganathan, Padhma Rangnekar, Vivek M. BE Balch, WE Der, CJ Hall, A TI Regulation of Par-4 by oncogenic Ras SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID PROTEIN PAR-4; APOPTOSIS; CELLS; CANCER; ACTIVATION; SUPPRESSION; INHIBITION; EXPRESSION; INTERACTS; PRODUCT AB Oncogenic Ras causes down-regulation of the proapoptotic tumor suppressor gene Par-4. Replenishment of the basal levels of Par-4 results in inhibition of Ras-inducible cellular transformation. Moreover, overexpression of Par-4 (twofold to fourfold over basal levels) results in apoptosis of cells expressing oncogenic Ras. Par-4 does not, on its own, induce apoptosis in immortalized or nontransformed cells. This chapter describes the key methods used for analysis of Par-4 down-regulation by oncogenic Ras, which can be extended to study most genes whose down-regulation by oncogenic Ras is critical for oncogenic transformation and cell survival. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY USA. Univ Kentucky, Dept Radiat Med, Lexington, KY USA. RP Vasudevan, KM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 24 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 422 EP 442 DI 10.1016/S0076-6879(05)07035-7 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800035 PM 16757343 ER PT J AU Davison, EH Pless, AP Gugliucci, MR King, LA King, DW Salgado, DM Spiro, A Bachrach, P AF Davison, EH Pless, AP Gugliucci, MR King, LA King, DW Salgado, DM Spiro, A Bachrach, P TI Late-life emergence of early-life trauma - The phenomenon of late-onset stress symptomatology among aging combat veterans SO RESEARCH ON AGING LA English DT Article DE aging; combat veterans; combat trauma; life-course effects of trauma; focus group research ID WORLD-WAR-II; MALE VIETNAM VETERANS; DISORDER SYMPTOMS; OLDER ADULTS; FOCUS GROUPS; MENS LIVES; RESILIENCE; HEALTH; PTSD; RETIREMENT AB This study aimed to provide preliminary evidence for, and explore potential antecedents and correlates of, a phenomenon observed in aging combat veterans termed late-onset stress symptomatology (LOSS). LOSS is a hypothesized phenomenon among older veterans who (a) experienced highly stressful combat events in early adulthood; (b) functioned successfully throughout their lives, with no chronic stress-related disorders; but (c) begin to register increased combat-related thoughts, feelings, reminiscences, memories, or symptoms commensurate with the changes and challenges of aging, sometimes decades after their combat experiences. Using a qualitative focus group methodology with 47 World War 11, Korean Conflict, and Vietnam War veterans, the authors obtained preliminary evidence for the presence of LOSS as defined, identified some of its features, revealed some normative late-life stressors that may precipitate LOSS, and uncovered potential intrapersonal risk and resilience factors for LOSS. The authors present illustrative quotations from the group discussions and discuss the implications and future directions of this research. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Mental Hlth Clin, Womens Hlth Sci Div, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ New England, Biddeford, ME USA. VA Med Ctr, Bedford, MA USA. RP Davison, EH (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Mental Hlth Clin, Womens Hlth Sci Div, Boston, MA USA. EM eve.davison@med.va.gov NR 54 TC 30 Z9 30 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD JAN PY 2006 VL 28 IS 1 BP 84 EP 114 DI 10.1177/0164027505281560 PG 31 WC Gerontology SC Geriatrics & Gerontology GA 992TS UT WOS:000233907500005 ER PT J AU Jennings, PA Aldwin, CM Levenson, MR Spiro, A Mroczek, DK AF Jennings, PA Aldwin, CM Levenson, MR Spiro, A Mroczek, DK TI Combat exposure, perceived benefits of military service, and wisdom in later life - Findings from the normative aging study SO RESEARCH ON AGING LA English DT Article DE wisdom; coping; combat trauma; perceived benefits; self-transcendence ID POSTTRAUMATIC-STRESS-DISORDER; PERSPECTIVE; RESILIENCE; VETERANS; VIETNAM; TRAUMA; HEALTH; GROWTH; TRANSCENDENCE; DEPRESSION AB Stress, even extremely traumatic stress, may pose both risks and benefits. Although combat can have lifelong negative consequences, the perception of positive benefits from military experience can mitigate the negative effects of combat on mental health. However, little research has examined the impact of trauma earlier in life on the development of positive adaptation, such as wisdom, later in life. The authors examined whether combat exposure and the perception of benefits from military experience, assessed in 1990, were associated with greater wisdom in later life, assessed in 2001 in 615 men from the Normative Aging Study men (mean age 74 years, SD = 6.8 years). A quadrilinear relationship between combat exposure and wisdom was found. Moderate levels of combat were associated with higher levels of wisdom. The perception of benefits and coping predicted wisdom. Thus, how one appraises and copes with problems may be more important in the prediction of positive adaptation than the simple occurrence of stress. C1 Univ Calif San Francisco, Cultivating Emot Balance Project, Hlth Psychol Program, San Francisco, CA 94143 USA. Oregon State Univ, Dept Human Dev & Family Sci, Corvallis, OR 97331 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Dent Med, Boston, MA 02215 USA. Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. Fordham Univ, Bronx, NY 10458 USA. RP Jennings, PA (reprint author), Univ Calif San Francisco, Cultivating Emot Balance Project, Hlth Psychol Program, San Francisco, CA 94143 USA. OI Jennings, Patricia/0000-0003-1026-1362 NR 72 TC 17 Z9 17 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD JAN PY 2006 VL 28 IS 1 BP 115 EP 134 DI 10.1177/0164027505281549 PG 20 WC Gerontology SC Geriatrics & Gerontology GA 992TS UT WOS:000233907500006 ER PT J AU Meissner, HH Hoo, GWS Khonsary, SA Mandelkern, M Brown, CV Santiago, SM AF Meissner, HH Hoo, GWS Khonsary, SA Mandelkern, M Brown, CV Santiago, SM TI Idiopathic pulmonary fibrosis: Evaluation with positron emission tomography SO RESPIRATION LA English DT Article DE pulmonary fibrosis; idiopathic interstitial pneumonia; positron emission tomography; usual interstitial pneumonitis ID RESOLUTION COMPUTED-TOMOGRAPHY; INTERSTITIAL LUNG-DISEASE; ALVEOLITIS; ACTIVATION; PNEUMONIA; DIAGNOSIS; MODEL AB Background: The pathogenesis of interstitial lung disease remains under investigation, but may be related to increased inflammatory or cellular activity. This activity may be detectable with physiologic imaging. Objectives: We investigated the role of physiologic imaging using F-18-2-fluoro-2-deoxy-D-glucose ((18)FDG)-positron emission tomography ( PET) scans in idiopathic pulmonary fibrosis (IPF). Methods: Seven male patients with histologically confirmed IPF underwent (18)FDG-PET scans. Scans were analyzed qualitatively and interpreted as positive or negative. Patients also underwent pulmonary function tests and computed tomography (CT) scans. Results: The average total lung capacity was 71 +/- 22% predicted ( mean +/- SD) and diffusing capacity for carbon monoxide was 44 +/- 14% predicted. All had changes consistent with IPF on chest CT and 2 patients had ground glass attenuation. Six of seven patients (86%) had a positive (18)FDG-PET scan. Changes in the (18)FDG-PET scan were seen in 1 patient corresponding to changes in clinical status. Conclusions: Our findings suggest that (18)FDG-PET scans may be helpful in the evaluation of IPF. Increased activity suggests active disease and changes in response to therapy. Copyright (C) 2006 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Div Nucl Med, Los Angeles, CA USA. RP Santiago, SM (reprint author), W Los Angeles VA Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Silverio.santiago@med.va.gov NR 24 TC 31 Z9 32 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PY 2006 VL 73 IS 2 BP 197 EP 202 DI 10.1159/000088062 PG 6 WC Respiratory System SC Respiratory System GA 023LD UT WOS:000236127300013 PM 16141712 ER PT J AU Sandberg, MA Gaudio, AR AF Sandberg, MA Gaudio, AR TI Reading speed of patients with advanced retinitis pigmentosa or choroideremia SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE choroideremia; contrast sensitivity; reading; retinitis pigmentosa; visual acuity; visual field ID MULTIFOCAL INTRAOCULAR LENSES; LOW-VISION; CONTRAST SENSITIVITY; VISUAL FUNCTION; PSYCHOPHYSICS; PERFORMANCE AB Purpose: To quantify, account for, and enhance the reading speed of patients with generalized retinal degeneration and small central visual fields. Methods: Thirty-three patients with retinitis pigmentosa or choroideremia and 12 normal controls participated in the study. The patients had visual acuities of 20/200 or better, central visual field diameters of <= 20 degrees, and log(10) contrast sensitivities of <= 1.65. Reading speed was measured by having participants silently read timed sentences presented with differing font size, font type (Times vs. Courier, and text polarity (standard black text on a white background vs. reversed white text on a black background) and then recall that text aloud. Results: The patients' mean reading speed for standard polarity text using the Times font and their optimal font size was 43% of normal (P < 0.001). Patient reading speed was significantly related to visual acuity (r(2) = 0.44; P < 0.001) and to contrast sensitivity (r(2) = 0.68; P < 0.001) but not to central visual field diameter. In a multiple regression model, only contrast sensitivity by itself was a strong independent predictor of patient reading speed, although visual acuity and visual field in combination did nearly as well. On average, the patients read significantly faster with the Times font than with the Courier font (P < 0.001). The percentage improvement in reading speed with reverse polarity text was most related to contrast sensitivity (r(2) = 0.47; P < 0.001), and 83% of patients with log(10) contrast sensitivity of < 1.0 versus 36% with higher contrast sensitivity read faster with reverse polarity text (P = 0.02). Conclusion: Patients with retinitis pigmentosa or choroideremia and small central fields have, on average, impaired reading speed associated primarily with reduced contrast sensitivity, and those with very poor contrast sensitivity will most likely benefit from reversing text polarity. C1 Harvard Univ, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM masandberg@aol.com NR 18 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2006 VL 26 IS 1 BP 80 EP 88 DI 10.1097/00006982-200601000-00013 PG 9 WC Ophthalmology SC Ophthalmology GA 004YO UT WOS:000234788800013 PM 16395143 ER PT J AU Cheng, J Kydd, AR Nakase, K Noonan, KM Murakami, A Tao, H Zhu, Q Marasco, WA AF Cheng, Jihua Kydd, Andre R. Nakase, Koichi Noonan, Kristin M. Murakami, Akikazu Tao, Hong Zhu, Quan Marasco, Wayne A. TI Negative regulation of the SH2-homologycontaining protein-tyrosine phosphatase-1 (Shp-1) P2 promoter by the HTLV-1 tax oncoprotein SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Cheng, Jihua; Kydd, Andre R.; Nakase, Koichi; Noonan, Kristin M.; Murakami, Akikazu; Tao, Hong; Zhu, Quan; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Cheng, Jihua; Nakase, Koichi; Zhu, Quan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM wayne_marasco@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P12 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000121 ER PT J AU Freund, NT Sui, J Marasco, WA Gershoni, JM AF Freund, Natalia Tarnovitski Sui, Jianhua Marasco, Wayne A. Gershoni, Jonathan M. TI Epitope-based vaccines: SARS - a model SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Freund, Natalia Tarnovitski; Gershoni, Jonathan M.] Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Canc Immunol, Boston, MA USA. [Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P62 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000171 ER PT J AU Lieberman, J AF Lieberman, Judy TI Harnessing RNA interference to prevent or treat HSV-2 and HIV SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Lieberman, Judy] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S48 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000049 ER PT J AU Pereyra, F Addo, MM Kaufmann, DE Miura, T Rathod, A Baker, B Trocha, A Ueda, P Rosenberg, R Cohen, D Stone, D Liu, Y Wrin, T Buchbinder, S Petropoulos, CJ Rosenberg, E Walker, BD AF Pereyra, Florencia Addo, Marylyn M. Kaufmann, Daniel E. Miura, Toshiyuki Rathod, Almas Baker, Brett Trocha, Alicja Ueda, Peggy Rosenberg, Rachel Cohen, Daniel Stone, David Liu, Yang Wrin, Terri Buchbinder, Susan Petropoulos, Christos J. Rosenberg, Eric Walker, Bruce D. TI Elite control of HIV infection: implications for vaccines SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pereyra, Florencia; Addo, Marylyn M.; Kaufmann, Daniel E.; Miura, Toshiyuki; Rathod, Almas; Baker, Brett; Trocha, Alicja; Ueda, Peggy; Rosenberg, Rachel; Rosenberg, Eric; Walker, Bruce D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Pereyra, Florencia; Addo, Marylyn M.; Kaufmann, Daniel E.; Miura, Toshiyuki; Rathod, Almas; Baker, Brett; Trocha, Alicja; Ueda, Peggy; Rosenberg, Rachel; Rosenberg, Eric; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. [Pereyra, Florencia; Walker, Bruce D.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Cohen, Daniel] Fenway Community Hlth Care Ctr, Boston, MA 02115 USA. [Stone, David] Lemuel Shattuck Hosp, Boston, MA 02130 USA. [Liu, Yang; Wrin, Terri; Petropoulos, Christos J.] Monogram Biosci Inc, San Francisco, CA 94080 USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. NR 0 TC 0 Z9 0 U1 2 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 PY 2006 VL 3 SU 1 MA S16 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000017 ER PT J AU Pizzato, M Helander, A Popova, E Calistri, A Zamborlini, A Palu, G Gottlinger, H AF Pizzato, Massimo Helander, Anna Popova, Elena Calistri, Arianna Zamborlini, Alessia Palu, Giorgio Goettlinger, Heinrich TI The enhancement of HIV-1 infectivity by Nef depends on dynamin 2 SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pizzato, Massimo; Calistri, Arianna; Zamborlini, Alessia; Palu, Giorgio] Univ Padua, Inst Microbiol, I-35100 Padua, Italy. [Pizzato, Massimo; Helander, Anna; Popova, Elena; Calistri, Arianna; Zamborlini, Alessia; Goettlinger, Heinrich] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pizzato, Massimo] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis, London, England. EM heinrich.gottlinger@umassmed.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S96 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000097 ER PT J AU Reinherz, EL Keskin, D Qiao, Z Kim, M AF Reinherz, E. L. Keskin, D. Qiao, Z. Kim, M. TI Misguiding cues used by HIV to thwart protective immunity SO RETROVIROLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 PY 2006 VL 3 SU 1 MA S24 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000025 ER PT J AU Zhou, TQ Xu, L Dey, B Hessell, AJ Majeed, S Van Ryk, D Xiang, SH Yang, XZ Zhang, MY Zwick, MB Arthos, J Burton, DR Dimitrov, DS Sodroski, J Wyatt, R Nabel, GJ Kwong, PD AF Zhou, Tongqing Xu, Ling Dey, Barna Hessell, Ann J. Majeed, Shahzad Van Ryk, Donald Xiang, Shi-Hua Yang, Xinzhen Zhang, Mei-Yun Zwick, Michael B. Arthos, James Burton, Dennis R. Dimitrov, Dimiter S. Sodroski, Joseph Wyatt, Richard Nabel, Gary J. Kwong, Peter D. TI Design clues from functional constraints and broadly neutralizing antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhou, Tongqing; Xu, Ling; Dey, Barna; Majeed, Shahzad; Wyatt, Richard; Nabel, Gary J.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Hessell, Ann J.; Zwick, Michael B.; Burton, Dennis R.] Scripps Res Inst, La Jolla, CA USA. [Van Ryk, Donald; Arthos, James] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Xiang, Shi-Hua; Yang, Xinzhen; Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Mei-Yun; Dimitrov, Dimiter S.] NCI, Ctr Canc Res & Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S22 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000023 ER PT J AU Eisenstein, EM Eisenstein, D AF Eisenstein, E. M. Eisenstein, D. TI A behavioral homeostasis theory of habituation and sensitization: II. Further developments and predictions SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE habituation; sensitization; learning; instinct; circadian; homeostasis; dementia; evolution ID GALVANIC SKIN-RESPONSE; SYNAPTIC PLASTICITY; KAIC PHOSPHORYLATION; MAIN CHARACTERISTICS; APLYSIA-CALIFORNICA; ALARM CALLS; PHASE-ANGLE; CONDUCTANCE; COCKROACH; MICROORGANISMS AB Habituation may be viewed as a decremental behavioral change to iterative stimuli of little immediate relevance. It is observed from protozoa to humans, indicating its evolutionary significance /24,25/. If habituation is interpreted as the process of filtering out unimportant repetitive stimuli, then how should sensitization be interpreted? The 'behavioral homeostasis theory' of these two behaviors is based on the notion that organisms at a high level of 'alertness' prior to experiencing a new iterative stimulus will show a large initial response followed by a decrement (habituation) if the stimulus is of little significance. Conversely, the same organism at a low level of 'alertness' will show a small initial response to the same stimulus followed by an increase in 'alertness' and a larger response to the next stimulus (sensitization) in order to receive enough information to assess its significance. Circadian rhythmicity is hypothesized to play a role in determining 'alertness' to a new iterative stimulus at any given time. The level of responsiveness in initial habituaters and sensitizers, as an asymptote is approached, is a balance between being too 'alert' to an unimportant stimulus and missing other significant stimuli, and being too 'un-alert' and missing a change in the relevance of the present iterative stimulus. The concept of 'behavioral homeostasis' includes behaviors beyond habituation and sensitization across phylogeny. It includes instinctive as well as learned, and group as well as individual behavior. Such behavioral homeostatic processes to optimize detection and assessment of constantly occurring external stimuli are critical for organism survival. Clinical implications of this theory are also examined. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Eisenstein, EM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM edward.eisenstein@med.va.gov NR 71 TC 17 Z9 17 U1 2 U2 9 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2006 VL 17 IS 5 BP 533 EP 557 PG 25 WC Neurosciences SC Neurosciences & Neurology GA 117OJ UT WOS:000242882300004 PM 17180878 ER PT S AU Chen, IA Hanczyc, MM Sazani, PL Szostak, JW AF Chen, Irene A. Hanczyc, Martin M. Sazani, Peter L. Szostak, Jack W. BE Gesteland, RF Cech, TR Atkins, JF TI Protocells: Genetic Polymers Inside Membrane Vesicles SO RNA WORLD, THIRD EDITION SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID CATALYZED RNA POLYMERIZATION; IN-VITRO EVOLUTION; MURCHISON CARBONACEOUS CHONDRITE; LARGE UNILAMELLAR VESICLES; NUCLEIC-ACID STRUCTURE; MONOCARBOXYLIC ACIDS; PHOSPHOLIPID-VESICLES; GIANT LIPOSOMES; LIGASE RIBOZYME; PHASE-BEHAVIOR C1 [Chen, Irene A.; Szostak, Jack W.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Hanczyc, Martin M.; Sazani, Peter L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Chen, Irene A.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Chen, IA (reprint author), Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. NR 134 TC 13 Z9 14 U1 1 U2 13 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-739-6 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 43 BP 57 EP 88 PG 32 WC Biology SC Life Sciences & Biomedicine - Other Topics GA BNJ34 UT WOS:000274736900006 ER PT S AU Spencer, RJ Lee, JT AF Spencer, Rebecca J. Lee, Jeannie T. BE Gesteland, RF Cech, TR Atkins, JF TI Large Noncoding RNAs in Mammalian Gene Dosage Regulation SO RNA WORLD, THIRD EDITION SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID X-CHROMOSOME INACTIVATION; IMPRINTED ANTISENSE RNA; EMBRYONIC STEM-CELLS; MOUSE XIST GENE; REPRESSIVE HISTONE METHYLATION; BECKWITH-WIEDEMANN-SYNDROME; POLYCOMB GROUP-COMPLEXES; BETA-GLOBIN LOCUS; INTERGENIC TRANSCRIPTION; H19 GENE C1 [Spencer, Rebecca J.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Spencer, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. NR 153 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-739-6 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 43 BP 595 EP 630 PG 36 WC Biology SC Life Sciences & Biomedicine - Other Topics GA BNJ34 UT WOS:000274736900024 ER PT J AU Bhan, I Chen, EJ Bazari, H AF Bhan, I Chen, EJ Bazari, H TI Isolation of Cardiobacterium hominis from the peritoneal fluid of a patient on continuous ambulatory peritoneal dialysis SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material AB Cardiobacterium hominis, an uncommon cause of bacterial endocarditis, is rarely implicated in infections outside the vascular system. We report the isolation of C. hominis from the peritoneal fluid of a patient on continuous ambulatory peritoneal dialysis with a presentation suggestive of peritonitis but no evidence of infective endocarditis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02114 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. RP Bhan, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Div, GRB 1003,55 Fruit St, Boston, MA 02114 USA. EM ibhan@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2006 VL 38 IS 4 BP 301 EP 303 DI 10.1080/00365540500349026 PG 3 WC Infectious Diseases SC Infectious Diseases GA 041KO UT WOS:000237455300011 PM 16709531 ER PT J AU Alam, HB AF Alam, H. B. TI An update on fluid resuscitation SO SCANDINAVIAN JOURNAL OF SURGERY LA English DT Review DE resuscitation; shock; fluids; blood; plasma; hypertonic saline; cellular injury; hypothermia; gene transcription; apoptosis; inflammation; immune activation ID HYPERTONIC SALINE RESUSCITATION; II CLINICAL-TRIAL; ADHESION MOLECULE-1 EXPRESSION; HYPOTHERMIC CIRCULATORY ARREST; ABDOMINAL COMPARTMENT SYNDROME; EXSANGUINATION CARDIAC-ARREST; CONVENTIONAL RINGERS SOLUTION; CRITICALLY ILL PATIENTS; RISK SURGICAL-PATIENTS; PROGRAMMED CELL-DEATH AB Hemorrhagic shock is the leading cause of death in civilian and military trauma. Effective hemorrhage control and better resuscitation strategies have the potential of saving lives. However, if not performed properly, resuscitation can actually exacerbate cellular injury caused by hemorrhagic shock, and the type of fluid used for resuscitation plays an important role in this injury pattern. It is logical to prevent this cellular injury through wiser resuscitation strategies than attempting immunomodulation after the damage has already occurred. It is important to recognize that unlike numerous other variables, resuscitation is completely under our control. We decide who, when and how should get resuscitated. This paper summarizes data from a number of studies to illustrate the differential effects of commonly used resuscitation fluids on cellular injury, and how these relate to clinical practice. In addition, some novel resuscitation strategies are described that may become clinically available in the near future. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 119 TC 17 Z9 18 U1 0 U2 1 PU FINNISH SURGICAL SOC PI HELSINKI PA MAKELANKATU 2 C, PO BOX 49, SF-00501 HELSINKI, FINLAND SN 1457-4969 J9 SCAND J SURG JI Scand. J. Surg. PY 2006 VL 95 IS 3 BP 136 EP 145 PG 10 WC Surgery SC Surgery GA 092KR UT WOS:000241096000002 PM 17066606 ER PT J AU Spencer, KM McCarley, RW AF Spencer, KM McCarley, RW TI Gamma-band EEG measures of hemispheric function and integration in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM kevin_spencer@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 12 EP 13 PG 2 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524700025 ER PT J AU Dracheva, S Davis, KL Chin, B Woo, DA Haroutunian, V AF Dracheva, S Davis, KL Chin, B Woo, DA Haroutunian, V TI Myelin-associated MRNA and protein expression deficits in the anterior cingulate cortex and hippocampus of schizophrenia patients: Possible link with SOX10 methylation status SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. EM stella.dracheva@mssm.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 46 EP 46 PG 1 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524700104 ER PT J AU White, T Karatekin, C Pardo, J Manoach, DS Schmidt, M Schulz, SC AF White, T Karatekin, C Pardo, J Manoach, DS Schmidt, M Schulz, SC TI Developmental differences in working memory load from childhood through young adulthood SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 Univ Minnesota, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM twhite@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 118 EP 118 PG 1 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524700287 ER PT J AU Kubicki, M Nestor, P Connor, E Ungar, L Niznikiewicz, M McCarley, RW Shenton, ME AF Kubicki, M Nestor, P Connor, E Ungar, L Niznikiewicz, M McCarley, RW Shenton, ME TI Relationship between color stroop performance and cingulum bundle diffusion anisotropy in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat NeuroImaging Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Clin Neurosci Div, Lab Neurosci,Boston VA Healthcare Syst,Brockton D, Boston, MA 02115 USA. EM kubicki@bwh.harvard.edu NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 160 EP 161 PG 2 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524700396 ER PT J AU Harlow, BL Vitonis, AF Joffe, H Sparen, P Cnattingius, S Hultman, CM AF Harlow, BL Vitonis, AF Joffe, H Sparen, P Cnattingius, S Hultman, CM TI Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior pre-pregnancy or prenatal psychiatric hospitalizations SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal Psychiat Res Unit, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. EM Par.Sparen@ki.se NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 186 EP 186 PG 1 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524701016 ER PT J AU Deeg, HJ Antin, JH AF Deeg, HJ Antin, JH TI The clinical spectrum of acute graft-versus-host disease SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; SKIN EXPLANT MODEL; MATCHED SIBLING DONORS; CENTRAL-NERVOUS-SYSTEM; RISK-FACTORS; ENGRAFTMENT SYNDROME; GENE POLYMORPHISMS; UNRELATED DONORS C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Deeg, HJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM jdeeg@fhcrc.org FU NCI NIH HHS [CA18029, CA15704]; NHLBI NIH HHS [HL36444] NR 83 TC 42 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2006 VL 43 IS 1 BP 24 EP 31 DI 10.1053/j.seminhematol.2005.09.003 PG 8 WC Hematology SC Hematology GA 003MT UT WOS:000234687000004 PM 16412786 ER PT J AU Zhang, M Chakravarti, A AF Zhang, M Chakravarti, A TI Novel radiation-enhancing agents in malignant gliomas SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; DIAGNOSED GLIOBLASTOMA-MULTIFORME; ACTIVATED PROTEIN-KINASE; ADJUVANT TEMOZOLOMIDE; MEDIATES RESISTANCE; PROGNOSTIC-FACTORS; CANCER-THERAPY; EGF RECEPTOR; PHASE-II; CELLS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org NR 45 TC 18 Z9 19 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2006 VL 16 IS 1 BP 29 EP 37 DI 10.1016/j.semradonc.2005.08.004 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 002AZ UT WOS:000234585100005 PM 16378904 ER PT S AU Kronenberg, HM AF Kronenberg, Henry M. BE Zaidi, M TI PTHrP and skeletal development SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE parathyroid hormone-related protein; growth plate; chondrocytes; Indian hedgehog ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION; PARATHYROID-HORMONE; GROWTH-PLATE; PTH/PTHRP RECEPTOR; HYPERTROPHIC DIFFERENTIATION; CHONDROCYTE DIFFERENTIATION; BLOMSTRAND-CHONDRODYSPLASIA; INACTIVATING MUTATION; INDEPENDENT PATHWAYS AB Parathyroid hormone-related protein (PTHrP) participates in the regulation of endochondral bone development. After the cartilage mold is established in fetal life, perichondrial cells and chondrocytes at the ends of the mold synthesize PTHrP. This ligand then acts on PTH/PTHrP receptors on chondrocytes. As chondrocytes go through a program of proliferation and then further differentiation into post-mitotic, hypertrophic chondrocytes, PTHrP action keeps chondrocytes proliferating and delays their further differentiation. Indian hedgehog (Ihh) is synthesized by chondrocytes that have just stopped proliferating and is required for synthesis of PTHrP. The feedback loop between PTHrP and Ihh serves to regulate the pace of chondrocyte differentiation and the sites at which perichondrial cells first differentiate into osteoblasts. Activation of the PTH/PTHrP receptor leads to stimulation of both G(s) and G(q) family heterotrimeric G proteins. Genetic analyses demonstrate that G(s) activation mediates the action of PTRrP to keep chondrocytes proliferating, while Gq activation opposes this action. Downstream from G(s) activation, synthesis of the cyclin-cdk inhibitor, p57, is suppressed, thereby increasing the pool of proliferating chondrocytes. PTHrP's actions to delay chondrocyte differentiation are mediated by the phosphorylation of the transcription factor, SOX9, and by suppression of synthesis of mRNA encoding the transcription factor, Runx2. These pathways and undoubtedly others cooperate to regulate the pace of differentiation of growth plate chondrocytes in response to PTHrP. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 501,50 Blossom St, Boston, MA 02114 USA. EM hkronenberg@partners.org NR 38 TC 211 Z9 217 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 1 EP 13 DI 10.1196/annals.1346.002 PG 13 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200001 PM 16831900 ER PT S AU Abe, E AF Abe, Etsuko BE Zaidi, M TI Function of BMPs and BMP antagonists in adult bone SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE BMP; BMP antagonist; Wnt; catenin; osteoblast; bone remodeling ID MORPHOGENETIC PROTEINS; BETA-CATENIN; OSTEOBLAST DIFFERENTIATION; CELL-DIFFERENTIATION; TWISTED-GASTRULATION; NEGATIVE REGULATOR; SMAD-BINDING; TGF-BETA; NOGGIN; WNT AB The expression and function of BMPs and BMPs in bone tissues have been studied for a long time because of their remarkable activities. However, their biological functions in normal bone-remodeling in adults were not fully understood until recently. Advanced technologies using gene manipulation were used to study their roles in adulthood. In addition, findings of new BMP antagonists and the effect of Wnt-canonical pathways on bone features also provided new insights in bone studies. C1 CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol, Mt Sinai Bone Program, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Abe, E (reprint author), CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol, Mt Sinai Bone Program, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. EM etsuko.abe@mssm.edu NR 59 TC 37 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 41 EP 53 DI 10.1196/annals.1346.007 PG 13 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200005 PM 16831904 ER PT S AU Schipani, E AF Schipani, Ernestina BE Zaidi, M TI Hypoxia and HIF-1 alpha in chondrogenesis SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE hypoxia; HIF-1 alpha; VHL; VEGF; chondrocytes ID ENDOCHONDRAL BONE-FORMATION; INDUCIBLE FACTOR 1-ALPHA; GROWTH-PLATE; EPIPHYSEAL CHONDROCYTES; PROLYL HYDROXYLATION; SKELETAL DEVELOPMENT; CELL-PROLIFERATION; GENE-EXPRESSION; VEGF ISOFORMS; ANGIOGENESIS AB In endochondral bone development chondrocytes undergo proliferation, hypertrophic differentiation, mineralization of the surrounding matrix, death, blood vessel invasion, and finally replacement of cartilage with bone. The chondrocytic growth plate is a unique mesenchymal tissue, as it is avascular but it requires blood vessel invasion in order to be replaced by bone. We have recently provided evidence that the growth plate is hypoxic during fetal development. Adaptation to hypoxia is a critical event in numerous pathological settings, such as tumor progression and survival of tissues in which blood flow has been suddenly interrupted. One of the hallmarks of the response to hypoxia is activation of the transcription factor HIF-1 alpha. The von Hippel-Lindau (VHL) tumor suppressor protein is a component of a ubiquitin ligase promoting proteolysis of HIF-1 alpha. By using a genetic approach, we have demonstrated that VHL and HIF-1 alpha are critical regulators of endochondral bone development. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR048191] NR 46 TC 31 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 66 EP 73 DI 10.1196/annals.1346.009 PG 8 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200007 PM 16831906 ER PT S AU Roodman, GD AF Roodman, G. David BE Zaidi, M TI Regulation of osteoclast differentiation SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE osteoclasts; differentiation; autocrine; paracrine; cytokines ID KAPPA-B LIGAND; MESSENGER-RNA EXPRESSION; HUMAN MARROW CULTURES; GIANT-CELL TUMORS; LARGE T-ANTIGEN; BCL-X-L; BONE-RESORPTION; RECEPTOR ACTIVATOR; ANNEXIN-II; PARATHYROID-HORMONE AB The osteoclast (OCL) is derived from the cells in monocyte-macrophage lineage. The earliest identifiable OCL precursor is the granulocyte-macrophage colony-forming unit (CFU-GM), which gives rise to granulocytes, monocytes, and OCL. CFU-GM-derived cells then differentiate to committed OCL precursors, which are post-mitotic cells, and fuse to form multinucleated OCL. A variety of factors both positively and negatively regulate OCL formation and activity. These include growth factors, such as macrophage colony-simulating factor, which simulates the proliferation and prevents apoptosis of early OCL precursors, and RANK ligand (RANKL), which is the primary mediator of OCL formation. Most factors that induce OCL differentiation, such as PTHrP, IL-11, and prostaglandins, do so by inducing expression of RANKL on, the surface of immature osteoblasts. Osteoprotegerin is a decoy receptor that blocks RANKL activity. In addition, OCL produce autocrine-paracrine factors that regulate OCL formation, such as IL-6, which is produced at high levels by OCL in Paget's disease and increases OCL formation. We screened human and murine OCL cDNA libraries to identify autocrine-paracrine factors that regulate OCL activity. We identified annexin-II, MIP-1 alpha, ADAM8, eosinophil chemotactic factor, and OCL inhibitor factors 1 and 2 as factors involved in OCL formation. Most recently, we have identified the receptor for ADAM8, alpha(9)beta(1) integrin, which appears to be critical for normal OCL activity. OCL differentiation is controlled by exogenous hormones and cytokines as well as autocrine-paracrine factors that positively or negatively regulate OCL proliferation and differentiation. C1 Univ Pittsburgh, Sch Med Hematol Oncol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Sch Med Hematol Oncol, VA Pittsburgh Healthcare Syst, R&D 151-U,Room 2E-113,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 52 TC 113 Z9 121 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 100 EP 109 DI 10.1196/annals.1346.013 PG 10 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200011 PM 16831910 ER PT S AU Demay, MB AF Demay, Marie B. BE Zaidi, M TI Mechanism of vitamin D receptor action SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE vitamin D receptor; keratinocyte; knockout; alopecia; rickets; osteomalacia ID HAIR FOLLICLE DEVELOPMENT; MINERAL ION HOMEOSTASIS; TRANSGENIC MICE; KNOCKOUT MICE; D DEFICIENCY; HYPERTROPHIC CHONDROCYTES; ABLATED MICE; DIFFERENTIATION; EXPRESSION; RICKETS AB Studies in humans and in animal models have demonstrated that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for normal skeletal growth and maturation. Investigations were undertaken to address which consequences of vitamin D receptor deficiency are a direct result of impaired receptor-dependent hormone actions versus being due to metabolic changes. Vitamin D receptor (VDR) knockout mice were therefore generated. Investigations were performed in mice with abnormal mineral ion homeostasis, as well as in mice in which the development of abnormal mineral ion homeostasis was prevented by dietary means. VDR null mice had hypocalcemia, hyperparathyroidism, and hypophosphatemia in the first month of life. Rickets and osteomalacia are observed as well. Institution of a high-calcium, high-phosphorus, lactose-supplemented diet by the third week of life prevents abnormalities in mineral ion homeostasis. The bones of the VDR null mice with normal mineral ion homeostasis are indistinguishable from those of their wild-type littermates. The rachitic changes in the growth plates are also prevented by maintenance of normal mineral ion homeostasis. Investigations into the pathophysiological basis for the growth plate abnormalities in the VDR null mice with abnormal mineral ion,homeostasis demonstrated that impaired apoptosis of hypertrophic chondrocytes due to hypophosphatemia was the cause of rachitic changes. Studies investigating the cause of the alopecia demonstrate novel ligand-independent VDR actions in the keratinocyte. The skeletal effects of VDR ablation are therefore indirect and reflect absence of ligand-dependent receptor actions in the intestine. In contrast, the cutaneous phenotype of VDR ablation is a direct consequence of absence of ligand-independent VDR actions in epidermal keratinocytes. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK046974, DK46974] NR 38 TC 55 Z9 55 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 204 EP 213 DI 10.1196/annals.1346.026 PG 10 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200021 PM 16831920 ER PT S AU Garcia-Palacios, V Chung, HY Choi, SJ Kurihara, N Lee, YW Ehrlich, LA Collins, R Roodman, GD AF Garcia-Palacios, Veronica Chung, Ho Yeon Choi, Sun Jin Kurihara, Noriyoshi Lee, Yun Won Ehrlich, Lori A. Collins, Robert Roodman, G. David BE Zaidi, M TI Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing ICAM-1 expression SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE ECF-L; osteoclasts; ICAM-1 ID INTERCELLULAR-ADHESION MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; FACTOR RECEPTOR FAMILY; DIFFERENTIATION; PROTEIN; LECTIN; IDENTIFICATION; INFLAMMATION; INVOLVEMENT; PRECURSORS AB Eosinophil chemotactic factor-L (ECF-L) is a novel stimulator of osteoclast (OCL) formation that acts at the differentiation/fusion stage of OCL formation, and is a cofactor for RANK ligand (RANKL). We examined the effects of ECF-L on the intracellular signaling pathways utilized by RANKL, and on the expression of ICAM-1/LFA-1 to determine its mechanism of action. RAW 264.7 and bone marrow cells were treated with RANKL and/or ECF-L Fe protein to determine their effect on NF-kappa B and AP-1 activity. ECF-L by itself only modestly increased NF-kappa B binding and JNK activity in RAW 264.7 cells, which were further enhanced by RANKL. In contrast, ECF-L Fe increased LFA-1 alpha and ICAM-1 mRNA levels 1.8-fold in mouse marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation induced by 10(-10) M 1,25-(OH)(2)D-3, and ECF-L Fc. Furthermore, ECF-L Fc did not enhance OCL formation by ICAM-I knockout (KO) cells. Increased expression of ICAM-I by ECF-L appears to be critical for its effects on OCL formation. C1 Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA USA. Sungkyunkwan Univ, Dept Med, Seoul, South Korea. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Roodman, GD (reprint author), 111-H,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu FU NIAID NIH HHS [AI-32177]; NIAMS NIH HHS [R01-AR41336] NR 14 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 240 EP 243 DI 10.1196/annals.1346.048 PG 4 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200025 PM 16831924 ER PT S AU Juppner, H Linglart, A Frohlich, LF Bastepe, M AF Juppner, Harald Linglart, Agnes Frohlich, Leopold F. Bastepe, Murat BE Zaidi, M TI Autosomal-dominant pseudohypoparathyroidism type Ib is caused by different microdeletions within or upstream of the GNAS locus SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE pseudohypoparathyroidism (PHP); PHP type Ia (PHP-Ia); pseudo-PHP (pPHP); PHP type Ib (PHP-Ib); progressive osseous heteroplasia(POH); alpha-subunit of stimulatory G protein (Gs alpha); syntaxin 16 (STXI 6) ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; IMPRINTING CONTROL ELEMENT; STIMULATORY G-PROTEIN; GENE; MUTATIONS; DELETION; REGION; DEFECT AB The term pseudohypoparathyroidism (PHP) refers to the different disorders that are caused by mutations within GNAS or upstream of this complex genetic locus. GNAS gives rise to several different transcripts, including Gs alpha (alpha-subunit of heterotrimeric stimulatory G protein),XL alpha s (extra-large variant of Gs alpha), and several additional sense and antisense transcripts. The complexity of the GNAS locus is furthermore reflected by a parent-specific methylation pattern of most of its different promotors. PHP can be divided into two major groups, PHP type la (PHP-Ia) and PHP type Ib (PHP-Ib). PHP-Ia is caused by heterozygous mutations affecting one of the 13 GNAS exons encoding Gs alpha or by large intragenic deletions. In contrast, PHP-Ib is caused by heterozygous deletions within STX16, the gene-encoding syntaxin 16, which is located more than 220 kb upstream of GNAS; or by deletions within GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP, hormonal resistance develops only after maternal inheritance of the mutation, while paternal inheritance of the same molecular defect is not associated with endocrine abnormalities. In most familial cases of PHP-Ib, there is a loss of exon A/B methylation combined with active A/B transcription from both parental alleles, which leads to suppression of Gs alpha transcription in the proximal renal tubules and, therefore, PTH resistance. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Thier 5, Boston, MA 02114 USA. EM hjueppner@partners.org NR 25 TC 13 Z9 13 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 250 EP 255 DI 10.1196/annals.1346.029 PG 6 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200027 PM 16831926 ER PT S AU Rajendren, G Zhou, H Moonga, BS Zaidi, M Sun, L AF Rajendren, Gopalan Zhou, Hang Moonga, Baljit S. Zaidi, Mone Sun, Li BE Zaidi, M TI Restoration of bone mass in Hpg mouse by preoptic area grafting SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE osteoporosis; hypogonadism; gonadotropin-releasing hormone ID HYPOGONADAL FEMALE MICE; HORMONE DEFICIENCY; BRAIN GRAFTS; CELLS; MEN AB Hereditary hypogonadism in the hpg mouse, caused by a deletion mutation in the gonadotropin-releasing hormone (GnRH) gene, is associated with sterility, absent ovarian development, and undetectable circulating sex steroids. Eight-month-old female hpg mice had a significantly reduced bone mineral density (BMD) at the lumbar spine, femur, and tibia. In addition, the mice showed significant reductions in liver and kidney weight, with virtually nonexistent ovaries. Successfully transplanted hpg mice with preoptic area grafts contained GnRH-positive neurons, consistent with our previous experience, and the host median eminence was innervated by GnRH immunoreactive fibers. A return of reproductive function was evident from increased ovarian weight and vaginal cornification. Of note was that grafted hpg mice showed a complete reversal to baseline of their BMD measured at all three sites. This establishes that the low bone mass that occurs in old hpg mice can be fully and rapidly ameliorated by preoptic area grafting. C1 Mt Sinai Bone Program, Dept Med, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, New York, NY 10029 USA. RP Sun, L (reprint author), Mt Sinai Sch Med, Endocrinol 1055,1 Gustave L Levy Pl, New York, NY 10029 USA. EM mone.zaidi@mssm.edu; mone.zaidi@mssm.edu FU NIA NIH HHS [R01 AG14197, AG23176]; NIDDK NIH HHS [DK70526] NR 13 TC 6 Z9 9 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 341 EP 347 DI 10.1196/annals.1346.050 PG 7 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200036 PM 16831935 ER PT J AU Cordova, CA Said, BO McCarley, RW Baxter, MG Chiba, AA Strecker, RE AF Cordova, Christopher A. Said, Bishoy O. McCarley, Robert W. Baxter, Mark G. Chiba, Andrea A. Strecker, Robert E. TI Sleep deprivation in rats produces attentional impairments on a 5-choice serial reaction time task SO SLEEP LA English DT Article DE sleep; total sleep deprivation; attention; rat; serial reaction time ID BASAL FOREBRAIN; SELECTIVE ATTENTION; INTERINDIVIDUAL DIFFERENCES; COGNITIVE FUNCTIONS; DIVERGENT THINKING; CIRCADIAN-RHYTHMS; PREFRONTAL CORTEX; BEHAVIORAL STATE; PERFORMANCE; LESIONS AB Study Objectives: To develop a rodent model of the attentional dysfunction caused by sleep loss. Design: The attentional performance of rats was assessed after 4, 7, and 10 hours of total sleep deprivation on a 5-choice serial reaction time task, in which rats detect and respond to brief visual stimuli. Setting: The rats were housed, sleep deprived, and behaviorally tested in a controlled laboratory setting. Participants: Ten male Long-Evans rats were used in the study. Interventions: Rats were trained to criteria and subsequently tested in daily sessions of 100 trials at approximately 4:00 PM (lights on 8:00 AM-8:00 PM). Attentional performance was measured after 4, 7, 10 hours of total sleep deprivation induced by gentle handling. Results: Sleep deprivation produced a monotonic increase in response latencies across the 4-hour, 7-hour, and 10-hour deprivations. Sleep deprivation also led to increased omission errors, but the overall number of perseverative and premature responses was unchanged. Subgroups of rats were differentially affected in the number of omission errors and perseverative responses. Conclusions: The effects of sleep deprivation on rats are compatible with a range of human findings on the effects of sleepiness on selective attention, psychomotor vigilance, and behavioral control. Rats also exhibited differential susceptibility to the effects of sleep deprivation, consistent with 'trait-like' susceptibility that has been found in humans. These findings indicate the feasibility of using the 5-choice serial reaction time task as an animal model for investigating the direct links between homeostatic sleep mechanisms and resulting attentional impairments within a single animal subject. C1 Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92053 USA. Univ Calif Irvine, Irvine Sch Med, Irvine, CA 92717 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston VA Healthcare Syst, Boston, MA USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Cordova, CA (reprint author), Univ Calif San Diego, Dept Cognit Sci, 9500 Gilman Dr, La Jolla, CA 92053 USA. EM cordova@ucsd.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NHLBI NIH HHS [HL60292, P50 HL060292]; NIMH NIH HHS [MH070959, F31 MH070959, MH39683, R01 MH039683, R37 MH039683] NR 65 TC 27 Z9 27 U1 2 U2 4 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2006 VL 29 IS 1 BP 69 EP 76 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078SJ UT WOS:000240123400011 PM 16453983 ER PT J AU Alessi, CA Martin, JL Webber, AP Alam, T Josephson, KR Harker, JO AF Alessi, C. A. Martin, J. L. Webber, A. P. Alam, T. Josephson, K. R. Harker, J. O. TI More daytime sleeping among older people undergoing post-acute rehabilitation predicts worse functional recovery SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, GRECC, Sepulveda, CA USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S BP A111 EP A112 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700331 ER PT J AU Berka, C Westbrook, PR Lumicao, MN Olmstead, R Levendowski, DJ Davis, G Eric, S Braich, K Ramsey, CK AF Berka, C. Westbrook, P. R. Lumicao, M. N. Olmstead, R. DJ, Levendowski Davis, G. Eric, S. Braich, K. Ramsey, C. K. TI Influence of sleep-disordered breathing on neurocognitive functions pre- and posttreatment with CPAP SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Adv Brain Monitoring Inc, Carlsbad, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 616 BP A208 EP A209 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700620 ER PT J AU Boehmer, LN Mitchell, TM Zhou, Q Siegel, JM AF Boehmer, L. N. Mitchell, T. M. Zhou, Q. Siegel, J. M. TI Prokineticin-2 affects sleep rhythms SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Calif Los Angeles, Braiin Res Inst, Los Angeles, CA USA. VA GLAHS Sepulveda, North Hills, CA USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 50 BP A17 EP A17 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700052 ER PT J AU Braich, K Berka, C Westbrook, PR Lumicao, MN Olmstead, R Levendowski, DJ Davis, G Ramsey, CK Eric, S AF Braich, K. Berka, C. Westbrook, P. R. Lumicao, M. N. Olmstead, R. Levendowski, D. J. Davis, G. Ramsey, C. K. Eric, S. TI Evaluation of subjective measures of sleepiness in obstructive sleep APNEA patients pre- and post-treatment with CPAP and comparison to healthy controls SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Adv Brain Monitoring Inc, Carlsbad, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 576 BP A195 EP A196 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700580 ER PT J AU Christie, M McCarley, R Strecker, R AF Christie, M. McCarley, R. Strecker, R. TI The effect of experimentally induced sleep fragmentation on two tests of attention in rats SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Profess Sleep Soc C1 Harvard Univ, Sch Med, Brockton, MA 02401 USA. VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2006 VL 29 SU S MA 1068 BP A366 EP A366 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701445 ER PT J AU Diniz, BC Brown, EN Scammell, TE Kopell, N AF Diniz, Behn C. Brown, E. N. Scammell, T. E. Kopell, N. TI Mathematical modeling of fragmented sleepwake behavior in orexin knockout mice SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Diniz Behn, Cecilia/L-1643-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 664 BP A225 EP A225 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701042 ER PT J AU Gvilia, I McGinty, D Szymusiak, R AF Gvilia, I McGinty, D. Szymusiak, R. TI Accumulation of rapid eye movement sleep propensity in the rat: A role for wakefulness SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. I Beritashvili Inst Physiol, Tbilisi, Rep of Georgia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 342 BP A116 EP A117 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700343 ER PT J AU Gvilia, I Turner, A McGinty, D Szymusiak, R AF Gvilia, I. Turner, A. McGinty, D. Szymusiak, R. TI Expression of c-fos in the preoptic area during different levels of sleep drive SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. I Beritashvili Inst Physiol, Tbilisi, Rep of Georgia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 5 BP A2 EP A2 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700007 ER PT J AU Herbst, ED Metzler, T McCaslin, S Inslicht, S Neylan, T AF Herbst, E. D. Metzler, T. McCaslin, S. Inslicht, S. Neylan, T. TI Adaptation effects to sleep studies in participants with and without chronic posttraumatic stress disorder SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 972 BP A332 EP A333 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701349 ER PT J AU Jordan, AS Wellman, A Heinzer, R Schory, K Dover, L Malhotra, A White, DP AF Jordan, A. S. Wellman, A. Heinzer, R. Schory, K. Dover, L. Malhotra, A. White, D. P. TI Mechanisms of compensation for upper airway collapse during NREM sleep in obstructive sleep APNEA and healthy controls SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Brigham & Womens Hosp, Sleep Disorders Program, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 533 BP A181 EP A182 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700537 ER PT J AU Jordan, AS Eikermann, M Schory, K Dover, L Wellman, A Malhotra, A White, DP AF Jordan, A. S. Eikermann, M. Schory, K. Dover, L. Wellman, A. Malhotra, A. White, D. P. TI Upper airway muscle activity and lung volume during spontaneously occurring stable breathing periods in obstructive sleep APNEA SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Brigham & Womens Hosp, Sleep Disorders Program, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 534 BP A182 EP A182 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700538 ER PT J AU Juergens, TM AF Juergens, T. M. TI Anxiety and depression on the tolerance of a continuous positive airway pressure (CPAP) mask in split-night sleep studies SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Wisconsin Hosp, Dept Psychiat, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 982 BP A336 EP A336 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701359 ER PT J AU Juergens, TM Young, T AF Juergens, T. M. Young, T. TI The interaction of ApoE allele status and sleep disordered breathing on cognitive function SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Wisconsin Hosp & Clin, Dept Geriatr Psychiat, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Psychiat, Madison, WI USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 335 BP A113 EP A113 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700335 ER PT J AU Krystal, A Walsh, J Fava, M McCall, V Schaefer, K Rubens, R Wessel, T Caron, J Wilson, P Roth, T AF Krystal, A. Walsh, J. Fava, M. McCall, V. Schaefer, K. Rubens, R. Wessel, T. Caron, J. Wilson, P. Roth, T. TI Analysis of individual items of the Hamilton depression scale in a study of eszopiclone/fluoxetine co-therapy SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Duke Univ, Med Ctr, Durham, NC USA. St Lukes Hosp, Chesterfield, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Sepracor, Marlborough, MA USA. Henry Ford Sleep Disorders Ctr, Detroit, MI USA. RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 707 BP A240 EP A240 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701084 ER PT J AU Lu, J Sherman, D Chamberlin, NL Saper, CB AF Lu, J. Sherman, D. Chamberlin, N. L. Saper, C. B. TI Neuronal substrates of the descending reticular activating system-mesencephalic locomotion region and cataplexy SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 61 BP A20 EP A20 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700063 ER PT J AU Lu, J Sherman, D Saper, CB AF Lu, J. Sherman, D. Saper, C. B. TI Neuronal substrates of the ascending reticular activating system (ARAS) SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 58 BP A19 EP A19 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700060 ER PT J AU Lyamin, O Siegel, J AF Lyamin, O. Siegel, J. TI Cetacean sleep behavior varies with body size SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Calif Los Angeles, Dept Psychiat, North Hills, CA USA. Univ Calif Los Angeles, VA GLAHS Sepulveda, North Hills, CA USA. Utrish Dolphinarium, Moscow, Russia. NR 0 TC 1 Z9 1 U1 1 U2 7 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 115 BP A38 EP A38 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700117 ER PT J AU McCall, V Krystal, A Fava, M Rubens, R Schaefer, K Huang, H Amato, D Roth, T AF McCall, V Krystal, A. Fava, M. Rubens, R. Schaefer, K. Huang, H. Amato, D. Roth, T. TI Eszopiclone co-administered with fluoxetine for insomnia co-existing with major depressive disorder (MDD): Analysis by severity of insomnia SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Profess Sleep Soc C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sepracor, Marlborough, MA USA. Henry Ford Sleep Disorders Ctr, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2006 VL 29 SU S MA 734 BP A249 EP A249 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701111 ER PT J AU Pryaslova, J Lyamin, O AF Pryaslova, J. Lyamin, O. TI Behavioral sleep in the walrus SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. VA GLAHS Sepulveda, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 113 BP A37 EP A38 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700115 ER PT J AU Tartar, JL Legare, SL Cordeira, JW Bebis, AC Ward, CP McCarley, RW Strecker, RE AF Tartar, J. L. Legare, S. L. Cordeira, J. W. Bebis, A. C. Ward, C. P. McCarley, R. W. Strecker, R. E. TI Sleep fragmentation decreases anxiety related behavior while increasing corticosterone in rats SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Harvard Univ, Sch Med, Brockton, MA 02401 USA. Harvard Univ, VABHS, Brockton, MA 02401 USA. Stonehill Coll, Easton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 379 BP A128 EP A128 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700380 ER PT J AU Thomas, RJ Kwong, KK AF Thomas, R. J. Kwong, K. K. TI Circadian modulation of functional brain activation SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 155 BP A52 EP A52 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700156 ER PT J AU Weaver, EM Maynard, C AF Weaver, E. M. Maynard, C. TI Sleep apnea mortality in middle-aged versus geriatric veterans SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 637 BP A215 EP A215 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701014 ER PT B AU Welsh, CH Fugit, RV AF Welsh, Carolyn H. Fugit, Randolph V. BA LeeChiong, T BF LeeChiong, T TI MEDICATIONS THAT CAN CAUSE INSOMNIA SO SLEEP: A COMPREHENSIVE HANDBOOK LA English DT Article; Book Chapter ID SLEEP; TOXICITY C1 [Welsh, Carolyn H.; Fugit, Randolph V.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Welsh, CH (reprint author), Denver Vet Affairs Med Ctr, Denver, CO USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-471-75172-4 PY 2006 BP 103 EP 109 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BZE26 UT WOS:000301234900015 ER PT J AU Martin, JL Alessi, CA AF Martin, Jennifer L. Alessi, Cathy A. BA LeeChiong, T BF LeeChiong, T TI SLEEP IN INSTITUTIONALIZED OLDER ADULTS SO SLEEP: A COMPREHENSIVE HANDBOOK LA English DT Article; Book Chapter ID NURSING-HOME PATIENTS; ACTIVITY RHYTHM DISTURBANCES; ALZHEIMERS-DISEASE; CIRCADIAN-RHYTHMS; INTERVENTION; AGITATION; LIGHT; WAKEFULNESS; RESIDENTS; IMPROVE C1 [Martin, Jennifer L.; Alessi, Cathy A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Martin, JL (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-471-75172-4 PY 2006 BP 615 EP 619 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BZE26 UT WOS:000301234900081 ER PT J AU Rodriguez, KL Young, AJ AF Rodriguez, KL Young, AJ TI Patients' and healthcare providers' understandings of life-sustaining treatment: Are perceptions of goals shared or divergent? SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; end-of-life care; life-sustaining treatment; advance care planning; healthcare preferences; qualitative research; veterans ID ADVANCE DIRECTIVES; OF-LIFE; MODELS AB In this cross-sectional qualitative study, researchers performed in-depth, semistructured interviews with 30 pairs of patients and their primary care providers in an outpatient clinic of a large, urban Veterans Affairs (VA) medical center in the United States. During audiotaped interviews to assess their understanding of advance directive concepts, participants were asked what "life-sustaining treatment" means to them and why they think of it in the way they do. The findings indicate that patients and providers in the United States tend to view and discuss life-sustaining treatment in terms of four goals for end-of-life care: (1) extending the length of life, (2) improving the quality of life, (3) maintaining or improving specific biological functions, and (4) assisting the body for a temporary period of time. Patients thought providers were more concerned with extending the length of life than with quality-based outcomes, and patients often discussed life-sustaining treatment as acceptable means for short-term but not long-term use. Many providers indicated that they struggle with conflicting quality-based and physiologic care goals. The findings highlight the importance of eliciting patient preferences not only for specific types of treatment, such as cardiopulmonary resuscitation, but also for end-of-life care goals or desired health-related outcomes, such as maximizing the quantity of life. The findings also suggest that advance directives and patient-provider discussions that focus on acceptable health states and valued life activities may be better suited to patients' end-of-life care goals than those that focus on specific medical interventions. Published by Elsevier Ltd. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,Bldg 28,Room 1A129, Pittsburgh, PA 15240 USA. EM keri.rodriguez@med.va.gov NR 31 TC 24 Z9 24 U1 0 U2 0 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 JAN PY 2006 VL 62 IS 1 BP 125 EP 133 DI 10.1016/j.scoscimed.2005.05.023 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 995VG UT WOS:000234131900012 PM 15993530 ER PT J AU Colley, BJ O'Brien, TX AF Colley, Byron Judson, III O'Brien, Terrence X. TI Cardiac tamponade: Still being newly described SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Off Res & Dev, Charleston, SC USA. RP O'Brien, TX (reprint author), Med Univ S Carolina, Dept Med, 135 Rutledge Ave,Suite 1201,POB 250952, Charleston, SC 29425 USA. EM obriente@musc.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2006 VL 99 IS 1 BP 4 EP 4 DI 10.1097/01.smj.0000197043.02035.ec PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 095NK UT WOS:000241314400003 PM 16466106 ER PT J AU Khanna, G Lewonowski, K Wood, KB AF Khanna, G Lewonowski, K Wood, KB TI Initial results of anterior interbody fusion achieved with a less invasive bone harvesting technique SO SPINE LA English DT Article DE bone graft; trephine; fusion; lumbar ID LUMBAR FUSION; ILIAC BONE; GRAFT; COMPLICATIONS; DISTRACTION; MORBIDITY; SPINE; ILIUM; PAIN AB Study Design. A retrospective review. Objective. To review the initial experience using a trephine bone harvesting system from the local lumbar spine for use in anterior interbody fusions, analyzing fusion rates and complications. Summary of Background Data. Historically, autogenous bone for lumbar spine fusions has been procured from the iliac crest. No data exist regarding the use of a trephine bone harvesting system for obtaining cancellous bone locally from the lumbar spine for use in anterior interbody fusions. In this technique, the donor site is replaced with a corticocancellous humeral dowel. Methods. A total of 36 patients who underwent anterior lumbar interbody fusion were retrospectively reviewed. There were 56 interbody fusions performed using 36 trephine donor sites. Twenty individuals had the bone divided between 2 fusion levels, placed within allograft femoral rings, and 16 had the bone applied to 1 fusion level. Radiographs were analyzed for complications associated with the fibular dowel and time to interbody fusion. Results. By 6 months, 35 of 36 (97%) of the corticocancellous fibular dowels had incorporated. Two dowels migrated 3 mm, each without sequelae. Of 56 of interbody spaces, 50 (89%) were fused. Two eventually fused at 9 and 11 months, and 4 (7%) failed to unite by 15 months. Conclusion. Harvesting cancellous autograft anteriorly from the lumbar spine using a trephine technique appears to be safe and reliable, with satisfactory fusion rates. Iliac crest graft harvesting with its attendant morbidity is avoided. C1 Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp,Wang Ambulatory Care Ctr, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Kansas Orthopaed Ctr, Wichita, KS USA. RP Wood, KB (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp,Wang Ambulatory Care Ctr, Suite 503,15 Parkman St, Boston, MA 02114 USA. EM kbwood@partners.org NR 22 TC 7 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 1 PY 2006 VL 31 IS 1 BP 111 EP 114 DI 10.1097/01.brs.0000192724.82234.6f PG 4 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 998VD UT WOS:000234347100023 PM 16395187 ER PT J AU Lensch, MW Daheron, L Schlaeger, TM AF Lensch, M. William Daheron, Laurence Schlaeger, Thorsten M. TI Pluripotent stem cells and their niches SO STEM CELL REVIEWS LA English DT Review DE pluripotent stem cells; embryonic germ cells; embryonal carcinoma cells; stem cell niche; teratomas; transcriptional regulators; signal transduction ID HUMAN EMBRYONIC STEM; PRIMORDIAL GERM-CELLS; LEUKEMIA INHIBITORY FACTOR; EARLY MOUSE DEVELOPMENT; OF-THE-LITERATURE; SELF-RENEWAL; ES CELLS; TRANSCRIPTION FACTOR; IN-VITRO; RETINOIC ACID AB The ability of stem cells to self-renew and to replace mature cells is fundamental to ontogeny and tissue regeneration. Stem cells of the adult organism can be categorized as mono-, bi-, or multipotent, based on the number of mature cell types to which they can give rise. In contrast, pluripotent stem cells of the early embryo have the ability to form every cell type of the adult body. Permanent lines of pluripotent stem cells have been derived from preimplantation embryos (embryonic stem cells), fetal primordial germ cells (embryonic germ cells), and malignant teratocarcinomas (embryonal carcinoma cells). Cultured pluripotent stem cells can easily be manipulated genetically, and they can be matured into adult-type stem cells and terminally differentiated cell types in vitro, thereby, providing powerful model systems for the study of mammalian embryogenesis and disease processes. In addition, human embryonic stem cell lines hold great promise for the development of novel regenerative therapies. To fully utilize the potential of these cells, we must first understand the mechanisms that control pluripotent stem cell fate and function. In recent decades, the microenvironment or niche has emerged as particularly critical for stem cell regulation. In this article, we review how pluripotent stem cell signal transduction mechanisms and transcription factor circuitries integrate information provided by the microenvironment. In addition, we consider the potential existence and location of adult pluripotent stem cell niches, based on the notion that a revealing feature indicating the presence of stem cells in a given tissue is the occurrence of tumors whose characteristics reflect the normal developmental potential of the cognate stem cells. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Schlaeger, TM (reprint author), Childrens Hosp, Div Hematol Oncol, Karp Bldg RBO8215,1 Blackfan Circle, Boston, MA 02115 USA. EM schlaeger@enders.tch.harvard.edu NR 300 TC 42 Z9 49 U1 9 U2 72 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2006 VL 2 IS 3 BP 185 EP 201 DI 10.1007/s12015-006-0047-2 PG 17 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 167YQ UT WOS:000246489000004 PM 17625255 ER PT S AU Yoneyama, R Chemaly, ER Hajjar, RJ AF Yoneyama, R. Chemaly, E. R. Hajjar, R. J. BE Morser, J Nishikawa, SI Scholer, HR TI Tracking stem cells in vivo SO STEM CELLS IN REPRODUCTION AND IN THE BRAIN SE Ernst Schering Research Foundation Workshop LA English DT Proceedings Paper CT Workshop on Stem Cells in Reproduction and in the Brain CY SEP 01-03, 2005 CL Kobe, JAPAN SP Ernst Schering Res Fdn, Max Planck Soc, Riken Ctr Dev Biol ID MYOCARDIAL-INFARCTION; CONTRAST AGENTS; PROGENITOR CELLS; TRANSPLANTATION; GENE; FERUMOXIDES; ULTRASOUND; EXPRESSION; MIGRATION; THERAPY AB Stem cells have been targeted to many organ systems specifically to replace scarred organs and to rejuvenate diseased organs. Even though our understanding of the versatility of stem cells is slowly unraveling, tracking these cells as they enter the body has become a very important field of study. In this chapter, we review various modalities for imaging stem cells and assess the advantages and shortcomings of each technique. C1 [Yoneyama, R.; Chemaly, E. R.; Hajjar, R. J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,Room 4215, Charlestown, MA 02129 USA. RP Yoneyama, R (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,Room 4215, Charlestown, MA 02129 USA. EM rhajjar@partners.org NR 31 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-31436-9 J9 E SCHERING RES FDN W JI E Schering Res. Fdn. Workshop PY 2006 VL 60 BP 99 EP + PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Research & Experimental Medicine GA BEV68 UT WOS:000239627200008 ER PT J AU Rabinov, JD Cheng, LL Lee, PL Brisman, JL Loeffler, JS Cole, AJ Cosgrove, GR Bussiere, MR Chaves, T Gonzalez, RG AF Rabinov, J. D. Cheng, L. L. Lee, P. L. Brisman, J. L. Loeffler, J. S. Cole, A. J. Cosgrove, G. R. Bussiere, M. R. Chaves, T. Gonzalez, R. G. TI MR spectroscopic changes in the rat hippocampus following proton radiosurgery SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE radiosurgery; spectroscopy; MRI; proton beam ID MAGNETIC-RESONANCE-SPECTROSCOPY; GAMMA-KNIFE IRRADIATION; RECURRENT GLIOMA; RADIATION; BRAIN; SYSTEM; EXPERIENCE; EPILEPSY; THERAPY AB Purpose: To identify MR spectroscopic changes in the rat hippocampus following proton radiosurgery. Methods and Materials: A group of 12 rats were treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI at 4 months following treatment. An untreated animal was also studied. A 3" surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE 30/90). Volumetric analysis with custom software was done to evaluate areas of increased signal on T2 weighted images and the development of hydrocephalus was examined. Animals were sacrificed and specimens of the treated hippocampus were harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS) followed by histopathology of the tissue samples. Peak values of choline, creatine, N-acetyl aspartate and lipids were evaluated and compared. Results: Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on the untreated side in the 90 CGE animal likely because of mass effect, while it was seen in small degrees in the side of treatment in the 70 and 50 CGE animals. Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this time point using H and E stains. HRMAS showed spectroscopic changes in the surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical significance was not reached because of the small sample size. Conclusions: Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to identify metabolic changes induced by radiation. Studies built on these principles may help develop non-invasive MR spectroscopic methods to distinguish radiation changes from tumor recurrence. Copyright (c) 2006 S. Karger AG, Basel C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. JFK Med Ctr, New Jersey Neurosci Inst, Edison, NJ USA. Lahey Clin Fdn, Dept Neurosurg, Burlington, MA USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM jrabinov@partners.org NR 19 TC 8 Z9 10 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2006 VL 84 IS 4 BP 147 EP 154 DI 10.1159/000094862 PG 8 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 083EE UT WOS:000240438400004 PM 16899979 ER PT J AU Goldstein, JN Thomas, SH Frontiero, V Joseph, A Engel, C Snider, R Smith, EE Greenberg, SM Rosand, J AF Goldstein, JN Thomas, SH Frontiero, V Joseph, A Engel, C Snider, R Smith, EE Greenberg, SM Rosand, J TI Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage SO STROKE LA English DT Article DE anticoagulants; emergency medicine; intracerebral hemorrhage; warfarin ID RECOMBINANT FACTOR VIIA; SUBCUTANEOUS VITAMIN-K; ANTICOAGULANT TREATMENT; TIME-COURSE; REVERSAL; EFFICACY; STROKE; RISK; PHYTONADIONE; GUIDELINES AB Background and Purpose - Anticoagulation-related intracerebral hemorrhage (ICH) is often fatal, and rapid reversal of anticoagulation is the most appealing strategy currently available for treatment. We sought to determine whether particular emergency department (ED) interventions are effective in reversing coagulopathy and improving outcome. Methods - Consecutive patients with warfarin-related ICH presenting to an urban tertiary care hospital from 1998 to 2004 were prospectively captured in a database. ED records were retrospectively reviewed for dose and timing of fresh-frozen plasma (FFP) and vitamin K, as well as serial coagulation measures. After excluding patients with incomplete ED records, do-not-resuscitate orders established in the ED, initial international normalized ratio (INR) <= 1.4, and for whom no repeat INR was performed, 69 patients were available for analysis. The primary outcome was a documented INR <= 1.4 within 24 hours of ED presentation. Results - Patients whose INR was successfully reversed within 24 hours had a shorter median time from diagnosis to first dose of FFP (90 minutes versus 210 minutes; P = 0.02). In multivariable analysis, shorter time to vitamin K, as well as FFP, predicted INR correction. Every 30 minutes of delay in the first dose of FFP was associated with a 20% decreased odds of INR reversal within 24 hours (odds ratio, 0.8; 95% CI, 0.63 to 0.99). Dosing of FFP and vitamin K had no effect. No ED intervention was associated with improved clinical outcome. Conclusions - Time to treatment is the most important determinant of 24-hour anticoagulation reversal. Although additional study is required to determine the clinical benefit of rapid reversal of anticoagulation, minimizing delays in FFP administration is a prudent first step in emergency management of warfarin-related ICH. C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jgoldstein@partners.org RI Goldstein, Joshua/H-8953-2016; OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS42695-01, R01 NS042147-02] NR 29 TC 137 Z9 139 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 151 EP 155 DI 10.1161/01.STR.0000195047.21562.23 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500033 PM 16306465 ER PT J AU Steiner, T Rosand, J Diringer, M AF Steiner, T Rosand, J Diringer, M TI Intracerebral hemorrhage associated with oral anticoagulant therapy - Current practices and unresolved questions SO STROKE LA English DT Article DE etiology; intracerebral hemorrhage; oral anticoagulant agents; therapy; warfarin ID RECOMBINANT-FACTOR-VIIA; ACTIVATED FACTOR-VII; INTERNATIONAL NORMALIZED RATIO; FRESH-FROZEN PLASMA; INTRACRANIAL HEMORRHAGE; ATRIAL-FIBRILLATION; RISK-FACTORS; PROTHROMBIN COMPLEX; STROKE PREVENTION; WARFARIN THERAPY AB Background and Purpose - Life-threatening intracranial hemorrhage, predominantly intracerebral hemorrhage (ICH), is the most serious complication of oral anticoagulant therapy ( OAT), with mortality in excess of 50%. Early intervention focuses on rapid correction of coagulopathy in order to prevent continued bleeding. Summary of Review - This article reviews the epidemiology of OAT-associated ICH (OAT-ICH), and current treatment options, with the aim of providing a framework for future studies of unresolved questions. A number of acute treatments are available, but all have a significant risk of inducing thrombosis and other side effects, and vary in their rapidity of effect: vitamin K (very slow response time), fresh frozen plasma (slow response time, large volume of fluid required, transfusion-related acute lung injury), prothrombin complex concentrates, and recombinant activated factor VII. Current practice is to administer a combination of vitamin K and either fresh frozen plasma or prothrombin complex concentrates; the occasional use of recombinant activated factor VII has been reported. No prospective study has addressed the efficacy of, or outcomes from, the use of these practices. Conclusions - Current management of OAT-ICH is varied and not based on evidence from randomized controlled trials. Well-designed clinical trials are essential if we are to identify the effective acute treatments for OAT-ICH that are urgently needed. C1 Univ Heidelberg, Dept Neurol, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, Dept Neurol, Neurol Neurosurg Intens Care Unit, St Louis, MO USA. RP Steiner, T (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM thorsten_steiner@med.uni-heidelberg.de RI Diringer, Michael/C-1165-2008; Steiner, Thorsten/A-7391-2014 OI Diringer, Michael/0000-0003-2337-5537; NR 81 TC 161 Z9 167 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 256 EP 262 DI 10.1161/01.STR.0000196989.09900.f8 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500053 PM 16339459 ER PT J AU Tan, K Duquette, M Liu, JH Zhang, RG Joachimiak, A Wang, JH Lawler, J AF Tan, K Duquette, M Liu, JH Zhang, RG Joachimiak, A Wang, JH Lawler, J TI The structures of the thrombospondin-1 N-terminal domain and its complex with a synthetic pentameric heparin SO STRUCTURE LA English DT Article ID SULFATE PROTEOGLYCANS; BINDING DOMAIN; TYPE-1 REPEATS; PROTEIN; RECEPTOR; RECOGNITION; INTEGRIN; MODULES; GLYCOSAMINOGLYCANS; INTERNALIZATION AB The N-terminal domain of thrombospondin-1 (TSPN-1) mediates the protein's interaction with (1) glycosaminoglycans, calreticulin, and integrins during cellular adhesion, (2) low-density lipoprotein receptor-related protein during uptake and clearance, and (3) fibrinogen during platelet aggregation. The crystal structure of TSPN-1 to 1.8 angstrom resolution is a beta sandwich with 13 antiparallel beta strands and 1 irregular strand-like segment. Unique structural features of the N- and C-terminal regions, and the disulfide bond location, distinguish TSPN-1 from the laminin G domain and other concanavalin A-like lectins/glucanases superfamily members. The crystal structure of the complex of TSPN-1 with heparin indicates that residues R29, R42, and R77 in an extensive positively charged patch at the bottom of the domain specifically associate with the sulfate groups of heparin. The TSPN-1 structure and identified adjacent linker region provide a structural framework for the analysis of the TSPN domain of various molecules, including TSPs, NELLs, many collagens, TSPEAR, and kielin. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wang, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu; jlawler@bidmc.harvard.edu FU NHLBI NIH HHS [R01 HL049081, HL49081, HL68003, R01 HL068003-04, R01 HL068003, R01 HL049081-09, R01 HL049081-07] NR 50 TC 52 Z9 53 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JAN PY 2006 VL 14 IS 1 BP 33 EP 42 DI 10.1016/j.str.2005.09.017 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 003MA UT WOS:000234685100006 PM 16407063 ER PT J AU Barnwell, SS Earleywine, M AF Barnwell, Sara Smucker Earleywine, Mitch TI Simultaneous alcohol and cannabis expectancies predict simultaneous use SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article AB Background: Simultaneous use of alcohol and cannabis predicts increased negative consequences for users beyond individual or even concurrent use of the two drugs. Given the widespread use of the drugs and common simultaneous consumption, problems unique to simultaneous use may bear important implications for many substance users. Cognitive expectancies offer a template for future drug use behavior based on previous drug experiences, accurately predicting future use and problems. Studies reveal similar mechanisms underlying both alcohol and cannabis expectancies, but little research examines simultaneous expectancies for alcohol and cannabis use. Whereas research has demonstrated unique outcomes associated with simultaneous alcohol and cannabis use, this study hypothesized that unique cognitive expectancies may underlie simultaneous alcohol and cannabis use. Results: This study examined a sample of 2600 (66% male; 34% female) Internet survey respondents solicited through advertisements with online cannabis-related organizations. The study employed known measures of drug use and expectancies, as well as a new measure of simultaneous drug use expectancies. Expectancies for simultaneous use of alcohol and cannabis predicted simultaneous use over and above expectancies for each drug individually. Discussion: Simultaneous expectancies may provide meaningful information not available with individual drug expectancies. These findings bear potential implications on the assessment and treatment of substance abuse problems, as well as researcher conceptualizations of drug expectancies. Policies directing the treatment of substance abuse and its funding ought to give unique consideration to simultaneous drug use and its cognitive underlying factors. C1 [Barnwell, Sara Smucker] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Earleywine, Mitch] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. RP Barnwell, SS (reprint author), VA Greater Los Angeles Healthcare Syst, Mail Code 116B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM smucker@usc.edu; MEarleywine@albany.edu NR 31 TC 8 Z9 8 U1 3 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PY 2006 VL 1 AR 29 DI 10.1186/1747-597X-1-29 PG 9 WC Substance Abuse SC Substance Abuse GA V99JS UT WOS:000206717600028 PM 17034634 ER PT J AU Kertesz, SG Madan, A Wallace, D Schumacher, JE Milby, JB AF Kertesz, Stefan G. Madan, Alok Wallace, Dennis Schumacher, Joseph E. Milby, Jesse B. TI Substance abuse treatment and psychiatric comorbidity: do benefits spill over? analysis of data from a prospective trial among cocaine-dependent homeless persons SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article AB Background: Comorbid psychiatric illness can undermine outcomes among homeless persons undergoing addiction treatment, and psychiatric specialty care is not always readily available. The prognosis for nonsubstance abuse psychiatric diagnoses among homeless persons receiving behaviorally-based addiction treatment, however, is little studied. Results: Data from an addiction treatment trial for 95 cocaine-dependent homeless persons (1996-1998) were used to profile psychiatric diagnoses at baseline and 6 months, including mood-related disorders (e. g. depression) and anxiety-related disorders (e. g. post-traumatic stress disorder). Treatment interventions, including systematic reinforcement for goal attainment, were behavioral in orientation. There was a 32% reduction in the prevalence of comorbid non-addiction psychiatric disorder from baseline to 6 months, with similar reductions in the prevalence of mood (-32%) and anxiety-related disorders (-20%) (p = 0.12). Conclusion: Among cocaine-dependent homeless persons with psychiatric comorbidity undergoing behavioral addiction treatment, a reduction in comorbid psychiatric disorder prevalence was observed over 6 months. Not all participants improved, suggesting that even evidence-based addiction treatment will prove insufficient for a meaningful proportion of the dually diagnosed homeless population. C1 [Kertesz, Stefan G.; Schumacher, Joseph E.] Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL 35294 USA. [Kertesz, Stefan G.] Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL 35294 USA. [Madan, Alok] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Wallace, Dennis] Rho Fed Syst Inc, Chapel Hill, NC 27517 USA. [Milby, Jesse B.] Univ Alabama, Dept Psychol, Div Prevent Med, Birmingham, AL 35294 USA. RP Kertesz, SG (reprint author), Univ Alabama, Sch Med, Div Prevent Med, 1530 3rd Ave S MT 608, Birmingham, AL 35294 USA. EM skertesz@uab.edu; madal_99@yahoo.com; dwallace@rhoworld.com; jschumacher@mail.dopm.uab.edu; jmilby@uab.edu FU NIDA NIH HHS [R01-DA-08475, K23 DA015487, K23-DA-15487] NR 42 TC 7 Z9 9 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PY 2006 VL 1 AR 27 DI 10.1186/1747-597X-1-27 PG 8 WC Substance Abuse SC Substance Abuse GA V99JS UT WOS:000206717600026 PM 16965639 ER PT S AU Wong, KK Chang, S DePinho, RA AF Wong, Kwok-Kin Chang, Sandy DePinho, Ronald A. BE DeLange, T Lundblad, V Blackburn, E TI Modeling Cancer and Aging in the Telomerase-deficient Mouse SO TELOMERES, SECOND EDITION SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID COMPARATIVE GENOMIC HYBRIDIZATION; MAMMARY EPITHELIAL-CELLS; WERNER-SYNDROME; CHROMOSOMAL INSTABILITY; REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; IN-VIVO; DYSFUNCTIONAL TELOMERES; DYSKERATOSIS-CONGENITA; IONIZING-RADIATION C1 [Wong, Kwok-Kin; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chang, Sandy] Univ Texas MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 98 TC 0 Z9 0 U1 0 U2 3 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-734-1 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 45 BP 109 EP 138 PG 30 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNE02 UT WOS:000274252600006 ER PT J AU Zhou, W Lin, PH Bush, RL Terramani, TT Matsuura, JH Cox, M Peden, E Guerrero, M Silberfein, EJ Dardik, A Rosenthal, D Lumsden, AB AF Zhou, W Lin, PH Bush, RL Terramani, TT Matsuura, JH Cox, M Peden, E Guerrero, M Silberfein, EJ Dardik, A Rosenthal, D Lumsden, AB TI In situ reconstruction with cryopreserved arterial allografts for management of mycotic aneurysms or aortic prosthetic graft infections: a multi-institutional experience SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE aneurysm, infected/surgery; bacterial infections/complications/surgery; arteries/transplantation; blood vessel prosthesis/adverse effects; cryopreservation; prosthesis-related infections/surgery; staphylococcal infections/surgery; surgical wound intection/surgery; reoperation; transplantation, homologous ID SURGICAL-MANAGEMENT; REPLACEMENT; HOMOGRAFTS; MODEL AB We designed this study to evaluate a multi-institutional experience regarding the efficacy of cryopreserved aortic allografts in the treatment of infected aortic prosthetic grafts or mycotic aneurysms. We reviewed clinical data of all patients from 4 institutions who underwent in situ aortic reconstruction with cryopreserved allografts for either infected aortic prosthetic graft or mycotic aneurysms from during a 6-year period. Relevant clinical variables and treatment outcomes were analyzed. A total of 42 patients (37 men; overall mean age 63 +/- 13 years, range 41-74 years) were identified during this study period. Treatment indications included 34 primary aortic graft infections (81%), 6 mycotic aneurysms (22%), and 2 aortoenteric erosions (5%). Transabdominal and thoracoabdominal approaches were used in 38 (90%) and 4 patients (10%), respectively. Staphylococcus aureus was the most commonly identified organism (n=27,64%). Although there was no intraoperative death, the 30-day operative mortality was 17% (n=7). There were 21 (50%) nonfatal complications, including local wound infection (n=8), lower-extremity deep venous thrombosis (n=5), amputation (n=6), and renal failure requiring hemodialysis (n=2). The average length of hospital stay was 16.4 +/- 7 days. During a mean follow-up period of 12.5 months, reoperation for allograft revision was necessary in 1 patient due to graft thrombosis (6%). The overall treatment mortality rate was 21% (n=9). In situ aortic reconstruction with cryopreserved allografts is an acceptable treatment method in patients with infected aortic prosthetic graft or mycotic aneurysms. Our,,, study showed that mid-term graft-related complications such as reinfection or aneurysmal degeneration were uncommon. C1 Baylor Coll Med, Houston VAMC, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Surg, Div Vasc Surg, Atlanta, GA 30322 USA. Med Coll Georgia, Atlanta Med Ctr, Dept Surg, Div Vasc Surg, Atlanta, GA USA. Yale Univ, Sch Med, Dept Surg, Div Vasc Surg, New Haven, CT 06510 USA. RP Lin, PH (reprint author), Baylor Coll Med, Houston VAMC, Div Vasc Surg & Endovasc Therapy, 20002 Holcombe Blvd 112, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 25 TC 41 Z9 42 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 2006 VL 33 IS 1 BP 14 EP 18 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 022UC UT WOS:000236080500004 PM 16572862 ER PT J AU Scott, DL Diez, G Goldmann, WH AF Scott, David L. Diez, Gerold Goldmann, Wolfgang H. TI Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Review ID ACTIN-CAPPING PROTEIN; MUSCLE ALPHA-ACTININ; ARP2/3 COMPLEX; CRYSTAL-STRUCTURE; ACIDIC PHOSPHOLIPIDS; FERM DOMAIN; CYTOSKELETAL PROTEINS; TAIL DOMAIN; CONFORMATIONAL-CHANGE; VINCULIN ACTIVATION AB Background: Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein. Results: We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e. g., an amphipathic alpha-helix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties. Conclusion: At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography. C1 [Scott, David L.; Goldmann, Wolfgang H.] Harvard Univ, Sch Med, Renal Unit, Leukocyte Biol & Inflammat Program,Struct Biol Pr, Charlestown, MA 02129 USA. [Scott, David L.; Goldmann, Wolfgang H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Diez, Gerold; Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Ctr Med Phys & Technol, Biophys Grp, D-91052 Erlangen, Germany. RP Scott, DL (reprint author), Harvard Univ, Sch Med, Renal Unit, Leukocyte Biol & Inflammat Program,Struct Biol Pr, 149 13th St, Charlestown, MA 02129 USA. EM dscott1@partners.org; gdiez@biomed.uni-erlangen.de; wgoldmann@biomed.uni-erlangen.de RI Goldmann, Wolfgang/H-5572-2013 FU Deutsche Forschungsgemeinschaft (DFG) [Is25/8-1]; North Atlantic Treaty Organization (NATO) [CLG 978417] FX This work was funded by the Deutsche Forschungsgemeinschaft (DFG; Is25/8-1 to WHG) and North Atlantic Treaty Organization (NATO; CLG 978417 to WHG). We thank Dr. H. Banfic for helpful comments. WHG is currently on sabbatical in Germany. NR 121 TC 17 Z9 18 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PY 2006 VL 3 AR 17 DI 10.1186/1742-4682-3-17 PG 14 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V19ED UT WOS:000208054800017 PM 16569237 ER PT J AU Hwang, JJ Ghobrial, IM Anderson, KC AF Hwang, Janice Jin Ghobrial, Irene M. Anderson, Kenneth C. TI New frontiers in the treatment of multiple myeloma SO THESCIENTIFICWORLDJOURNAL LA English DT Review DE multiple myeloma; signaling pathways; novel therapy; interleukin-6 (IL-6); proteasome inhibitor; thalidomide ID ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; OVERCOMES DRUG-RESISTANCE; BONE-MARROW MICROENVIRONMENT; THALIDOMIDE PLUS DEXAMETHASONE; PROTEASOME INHIBITOR PS-341; LOW-DOSE THALIDOMIDE; ANTI-INTERLEUKIN-6 MONOCLONAL-ANTIBODY; HISTONE DEACETYLASE INHIBITION; RECEPTOR SUPER-ANTAGONIST AB Recent leaps in elucidating the biology of myeloma, particularly the intracellular pathways and the complex interaction with the bone marrow microenvironment, have resulted in an unprecedented surge of novel, targeted therapies and therapeutic regimens. There are currently over 30 new agents being tested in the treatment of multiple myeloma (MM). Many of these are novel, targeted agents that have demonstrated significant efficacy and prolonged survival. In this review, we summarize the current understanding of the mechanisms of action of novel therapies being tested in the preclinical and clinical settings in MM. These include agents that act directly on the intracellular signaling pathways, cell maintenance processes, and cell surface receptors. Finally, we present the clinical responses to some of these agents when used alone or in combination in clinical trials of patients with MM. Indeed, MM has become a model disease for the development of novel, therapeutic agents. C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM Kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [R01 CA133799, R01 CA133799-01A1]; PHS HHS [P01-78378, R0-1 50947] NR 231 TC 7 Z9 7 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2006 VL 6 BP 1475 EP 1503 DI 10.1100/tsw.2006.236 PG 29 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 227DF UT WOS:000250636700001 PM 17160337 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI The von Hippel-Lindau tumor suppressor gene: Roles in cancer and oxygen sensing SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID PROLYL HYDROXYLASE; HIF C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 990 EP 990 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200034 ER PT J AU Reddy, A Grueneberg, D Harlow, E Kaelin, W AF Reddy, Archana Grueneberg, Dorre Harlow, Ed Kaelin, William TI Untitled SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Broad Inst, Dept Biochem, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1009 EP 1010 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200057 ER PT J AU Marty, FM Rubin, RH AF Marty, FM Rubin, RH TI The prevention of infection post-transplant: the role of prophylaxis, preemptive and empiric therapy SO TRANSPLANT INTERNATIONAL LA English DT Review DE antimicrobial use; infection; preemptive; prevention; transplantation ID STEM-CELL TRANSPLANTATION; PNEUMOCYSTIS-CARINII-PNEUMONIA; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; URINARY-TRACT-INFECTION; TRIMETHOPRIM-SULFAMETHOXAZOLE; CYTOMEGALOVIRUS DISEASE; LIVER-TRANSPLANTATION; RANDOMIZED-TRIAL; HEPATITIS-C AB The close linkage of infection with the nature and intensity of the transplant immuno suppressive program has led to the concept of the therapeutic prescription. This has two components: an immunosuppressive one to prevent or treat rejection and graft-versus-host disease and an antimicrobial one to make it safe. This review provides a conceptual framework to approach the risk and risk periods for infection in solid organ and hematopoietic stem cell transplant recipients as well as an approach to antimicrobial use in this population. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Ctr Expt Pharmacol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Rubin, RH (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02215 USA. EM rhrubin@partners.org NR 50 TC 31 Z9 34 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD JAN PY 2006 VL 19 IS 1 BP 2 EP 11 DI 10.1111/j.1432-2277.2005.00218.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 013EI UT WOS:000235392200002 PM 16359371 ER PT B AU Jenkins, NT Mendez, PF Eagar, TW AF Jenkins, N. T. Mendez, P. F. Eagar, T. W. BE David, SA DebRoy, T Lippold, JC Smartt, HB Vitek, JM TI Effect of Arc Welding Electrode Temperature on Vapor and Fume Composition SO TRENDS IN WELDING RESEARCH, PROCEEDINGS LA English DT Proceedings Paper CT 7th International Conference on Trends in Welding Research CY MAY 16-20, 2005 CL Pine Mt, GA SP ASM ID ALLOYING ELEMENT VAPORIZATION; METAL VAPORIZATION; RATES; GENERATION; STEEL; MODEL; SIZE AB Welding fume composition is dependent on the temperature at the surface of a GMAW electrode. This temperature varies with welding parameters and affects the amount, composition, and type of fume. A thermodynamic analysis based on the superheating expected at the surface of the molten electrode tip is presented to help understand observed fume composition. C1 [Jenkins, N. T.] Massachusetts Gen Hosp, Charlestown, MA USA. RP Jenkins, NT (reprint author), Massachusetts Gen Hosp, Charlestown, MA USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU ASM INTERNATIONAL PI MATERIALS PARK PA 9503 KINSMAN RD, MATERIALS PARK, OH 44073 USA BN 978-0-87170-842-7 PY 2006 BP 491 EP 496 PG 6 WC Metallurgy & Metallurgical Engineering SC Metallurgy & Metallurgical Engineering GA BPT87 UT WOS:000279918300078 ER PT J AU Bell, DW Sordella, R Kwak, EL Godin-Heymann, N Sharma, SV Sgroi, DC Sequist, LV Lynch, TJ Settleman, J Haber, DA AF Bell, Daphne W. Sordella, Raffaella Kwak, Eunice L. Godin-Heymann, Nadia Sharma, Sreenath V. Sgroi, Dennis C. Sequist, Lecia V. Lynch, Thomas J. Settleman, Jeffrey Haber, Daniel A. TI Molecular targeted therapy of lung cancer. SO TUMOR BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Harvard Med Sch, Charlestown, MA USA. EM bell@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2006 VL 27 SU 2 PG 1 WC Oncology SC Oncology GA 120IR UT WOS:000243078700013 ER PT J AU Brown, AK Skates, S Sardesai, N Verch, T Glover, C DiSilvestro, P Granai, CO Moore, RG AF Brown, Amy K. Skates, Steven Sardesai, Niranjan Verch, Thorsten Glover, Curtis DiSilvestro, Paul Granai, C. O. Moore, Richard G. TI Development of a multiple marker assay using novel serum tumor markers for the detection of ovarian carcinoma. SO TUMOR BIOLOGY LA English DT Meeting Abstract C1 Program Womens Oncol, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fujirebio Diagnost Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2006 VL 27 SU 2 PG 1 WC Oncology SC Oncology GA 120IR UT WOS:000243078700040 ER PT B AU Hoffman, TJ Rold, TL Figueroa, SD Sieckman, GL Garrison, GC Winkelmann, CT Smith, CJ Perry, MC Volkert, WA AF Hoffman, T. J. Rold, T. L. Figueroa, S. Daibes Sieckman, G. L. Garrison, G. C. Winkelmann, C. T. Smith, C. J. Perry, M. C. Volkert, W. A. GP Medimond TI The gastrin releasing peptide receptor (BB2r) as a potential target for diagnostic and therapeutic radiopharmaceuticals SO UICC World Cancer Congress, Proceedings LA English DT Proceedings Paper CT World Cancer Congress of the International-Union-Against-Cancer (UICC) CY JUL 08-12, 2006 CL Washington, DC SP Int Union Against Canc ID PROSTATE-CANCER CELLS C1 Univ Missouri, Ellis Fischel Canc Ctr, Dept Internal Med, Dept Radiol & Vet Pathobiol,US Dept Vet Affairs, Columbia, MO 65201 USA. RP Hoffman, TJ (reprint author), Univ Missouri, Ellis Fischel Canc Ctr, Dept Internal Med, Dept Radiol & Vet Pathobiol,US Dept Vet Affairs, Columbia, MO 65201 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-318-9 PY 2006 BP 63 EP 67 PG 5 WC Oncology SC Oncology GA BGE15 UT WOS:000246257800013 ER PT B AU Hoffman, TJ Figueroa, SD Rold, TL Sieckman, GL Winkelmann, CT Ma, L Garrison, JC Volkert, WA AF Hoffman, T. J. Figueroa, S. D. Rold, T. L. Sieckman, G. L. Winkelmann, C. T. Ma, L. Garrison, J. C. Volkert, W. A. GP Medimond TI Molecular and anatomic imaging in tumor targeted radiopharmaceutical drug development SO UICC World Cancer Congress, Proceedings LA English DT Proceedings Paper CT World Cancer Congress of the International-Union-Against-Cancer (UICC) CY JUL 08-12, 2006 CL Washington, DC SP Int Union Against Canc C1 Univ Missouri, Dept Internal Med, Dept Radiol, US Dept Vet Affairs, Columbia, MO 65201 USA. RP Hoffman, TJ (reprint author), Univ Missouri, Dept Internal Med, Dept Radiol, US Dept Vet Affairs, Columbia, MO 65201 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-318-9 PY 2006 BP 69 EP 73 PG 5 WC Oncology SC Oncology GA BGE15 UT WOS:000246257800014 ER PT S AU Schmitt, F Potthast, A Stoeckel, B Triantafyllou, C Wiggins, CJ Wiggins, G Wald, LL AF Schmitt, Franz Potthast, Andreas Stoeckel, Bernd Triantafyllou, Christina Wiggins, Christopher J. Wiggins, Graham Wald, Lawrence L. BA Robitaille, PM Berliner, L BF Robitaille, PM Berliner, L TI ASPECTS OF CLINICAL IMAGING AT 7 T SO ULTRA HIGH FIELD MAGNETIC RESONANCE IMAGING SE Biological Magnetic Resonance LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; HIGH-FIELD MRI; VARYING MAGNETIC-FIELDS; HIGH-RESOLUTION MR; 8 TESLA; VASCULAR ANATOMY; HUMAN BRAIN; NOISE; BODY; TRANSMIT AB The intrinsic improvements in signal-to-noise ratio, spectral dispersion, and Susceptibility contrast with increasing static magnetic field strength, B-0, has spurred the development of MR technology from its very first application to clinical imaging. With maturing magnet, RF, and gradient technology, the clinical community has seen the static magnetic field of clinical systems increase from 0.2 to 1.5 to 3.0 T. Today, the "high field" label for human MR research describes initial experiences with 7, 8, and 9.4T systems. While currently primarily research instruments, this technology is bound to cross the boundary into the clinical diagnostic arena as key technical issues are solved and the methodology proves itself for addressing clinical issues. In this chapter we discuss the particular advantages and disadvantages of ultra high field systems for clinical imaging as well as some of the immediate technological challenges that must be solved to derive the full benefit of the extraordinary sensitivity of these systems, which has been glimpsed from their research use. C1 [Schmitt, Franz; Potthast, Andreas] Siemens Med Solut, Dept MREF, Erlangen, Germany. [Stoeckel, Bernd] Siemens Med Solut, Malvern, PA USA. [Triantafyllou, Christina; Wiggins, Christopher J.; Wiggins, Graham; Wald, Lawrence L.] Massachusetts Gen Hosp, Martinos Ctr, Dept Radiol, Charlestown, MA 02129 USA. RP Schmitt, F (reprint author), Siemens Med Solut, Dept MREF, Erlangen, Germany. EM franz.schmitt@siemens.com; Andreas.Potthast@siemens.com; Bernd.Stoeckel@siemens.com; christin@nmr.mgh.harvard.edu; wiggins@nmr.mgh.harvard.edu; gwiggins@nmr.mgh.harvard.edu; wald@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 NR 96 TC 2 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0192-6020 BN 978-0-387-34231-3 J9 BIOL MAGN RESON JI Biol. Magn. Reson. PY 2006 VL 26 BP 59 EP 103 D2 10.1007/978-0-387-49648-1 PG 45 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BKE11 UT WOS:000267857200004 ER PT S AU Wald, LL Fischl, B Rosen, BR AF Wald, Lawrence L. Fischl, Bruce Rosen, Bruce R. BA Robitaille, PM Berliner, L BF Robitaille, PM Berliner, L TI HIGH-RESOLUTION AND MICROSCOPIC IMAGING AT HIGH FIELD SO ULTRA HIGH FIELD MAGNETIC RESONANCE IMAGING SE Biological Magnetic Resonance LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE MICROSCOPY; ALZHEIMERS AMYLOID PLAQUES; MR MICROSCOPY; SENILE PLAQUES; IN-VIVO; NEUROFIBRILLARY TANGLES; TRANSGENIC MICE; CEREBRAL-CORTEX; PHASED-ARRAY; DISEASE C1 [Wald, Lawrence L.; Fischl, Bruce; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Wald, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu; bruce@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 NR 69 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0192-6020 BN 978-0-387-34231-3 J9 BIOL MAGN RESON JI Biol. Magn. Reson. PY 2006 VL 26 BP 343 EP 371 D2 10.1007/978-0-387-49648-1 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BKE11 UT WOS:000267857200011 ER PT B AU Dean, T Khatri, A Potetinova, Z Willick, G Gardella, TJ AF Dean, Thomas Khatri, Ashok Potetinova, Zhanna Willick, Gordon Gardella, Thomas J. BE Blondelle, SE TI Mechanism of interaction between the (17-31) binding domain of PTH and the PTH receptor SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID PARATHYROID-HORMONE PTH; RESIDUE-19; REGION; SITE C1 [Dean, Thomas; Khatri, Ashok; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Potetinova, Zhanna; Willick, Gordon] CNR, Inst Bio Sci, Ottawa, ON K1A 0R6, Canada. RP Dean, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 344 EP + DI 10.1007/978-0-387-26575-9_138 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800138 ER PT B AU Potetinova, Z Barbier, JR Gardella, TJ Dean, T Whitfield, JF Willick, GE AF Potetinova, Zhanna Barbier, Jean-Rene Gardella, Thomas J. Dean, Thomas Whitfield, James F. Willick, Gordon E. BE Blondelle, SE TI N-backbone methylations of parathyroid hormone (PTH) C-terminal region: Bioactivities and implications for PTH-receptor complex SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Potetinova, Zhanna; Barbier, Jean-Rene; Whitfield, James F.; Willick, Gordon E.] Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. [Gardella, Thomas J.; Dean, Thomas] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Potetinova, Z (reprint author), Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 617 EP + DI 10.1007/978-0-387-26575-9_271 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800271 ER PT B AU Potetinova, Z Barbier, JR Dean, T Gardella, TJ Willick, GE AF Potetinova, Zhanna Barbier, Jean-Rene Dean, Thomas Gardella, Thomas J. Willick, Gordon E. BE Blondelle, SE TI C-terminal modified parathyroid hormone: Effects on structure and activity SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID BIOLOGICAL-ACTIVITY; PEPTIDES; ANALOGS C1 [Potetinova, Zhanna; Barbier, Jean-Rene; Willick, Gordon E.] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. [Dean, Thomas; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Potetinova, Z (reprint author), Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 621 EP + DI 10.1007/978-0-387-26575-9_273 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800273 ER PT J AU Gerhard-Herman, M Gardin, JM Jaff, M Mohler, E Roman, M Naqvi, TZ AF Gerhard-Herman, Marie Gardin, Julius M. Jaff, Michael Mohler, Emile Roman, Mary Naqvi, Tasneem Z. TI Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology SO VASCULAR MEDICINE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; ASSISTED DUPLEX SONOGRAPHY; LONG-TERM PATENCY; CAROTID-ARTERY; FOLLOW-UP; DOPPLER ULTRASOUND; FEMOROPOPLITEAL ANGIOPLASTY; LOWER-EXTREMITIES; STENOSIS; ENDARTERECTOMY C1 Brigham & Womens Hosp, Vasc Diagnost Lab, Boston, MA 02115 USA. St John Hosp & Med Ctr, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. Cornell Univ, Weill Med Coll, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Gerhard-Herman, M (reprint author), Brigham & Womens Hosp, Vasc Diagnost Lab, L2-015B,75 Francis St, Boston, MA 02115 USA. EM mgerhard@partners.org NR 53 TC 39 Z9 41 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2006 VL 11 IS 3 BP 183 EP 200 DI 10.1177/1358863x06070516 PG 18 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 126CK UT WOS:000243489600010 PM 17288127 ER PT J AU Roman, MJ Naqvi, TZ Gardin, JM Gerhard-Herman, M Jaff, M Mohler, E AF Roman, Mary J. Naqvi, Tasneem Z. Gardin, Julius M. Gerhard-Herman, Marie Jaff, Michael Mohler, Emile TI Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology SO VASCULAR MEDICINE LA English DT Article ID INTIMA-MEDIA THICKNESS; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE ATHEROSCLEROSIS; ENDOTHELIUM-DEPENDENT DILATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CAROTID WALL THICKNESS; HEALTHY-YOUNG ADULTS; BRACHIAL-ARTERY; ESSENTIAL-HYPERTENSION; POSTMENOPAUSAL WOMEN C1 Cornell Univ, Weill Med Coll, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. St John Hosp & Med Ctr, Detroit, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. RP Roman, MJ (reprint author), Amer Soc Echocardiog, 1500 Sunday Dr,Suite 102, Raleigh, NC 27607 USA. EM mroman@med.cornell.edu NR 94 TC 64 Z9 71 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2006 VL 11 IS 3 BP 201 EP 211 DI 10.1177/1358863x06070511 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 126CK UT WOS:000243489600011 PM 17288128 ER PT S AU Lieu, SN Oh, DS Pisegna, JR Germano, PM AF Lieu, Song N. Oh, David S. Pisegna, Joseph R. Germano, Patricia M. BE Vaudry, H Laburthe, M TI Neuroendocrine tumors express PAC1 receptors SO VIP, PACAP, AND RELATED PEPTIDES: FROM GENE TO THERAPY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on VIP, PACAP and Related Peptides CY SEP 11-14, 2005 CL Rouen, FRANCE SP Conseil Reg Haute-Normandie, Agglomerat Rouen, Inst Fed Rech Multidisciplinaires Peptides, Inst Natl Sante Rech Med, Municipal Rouen, Sci Act Haute-Normandie, Tech Chime-Biol Sante, Univ Paris 7, Univ Rouen DE BON; carcinoid tumor; PACAP ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SPLICE VARIANTS; CANCER CELLS; I RECEPTOR; ANTAGONIST; SECRETION AB Neuroendocrine tumors (NETs) of the gastrointestinal tract can be grossly divided into two general types: carcinoid and pancreatic endocrine tumors. The former develop in the luminal intestine whereas the latter occur within the pancreas. To ascertain whether pituitary adenylate cyclase-activating polypeptide (PACAP) has a biological effect on the regulation of secretion or growth, we studied the well-established NET cell line, BON. BON cells have been shown previously to contain chromogranin A, neurotensin, and serotonin. In response to mechanical stimulation, BON cells have been demonstrated to release serotonin. The current article demonstrates that the high-affinity PAC1 receptor is expressed on the NET cell line BON. These results indicate that PACAP may regulate the biological release of peptides and serotonin from BON cells and that, like in solid tumors, PACAP could potentially stimulate the growth of BON cells. C1 Univ Calif Los Angeles, CURE, David Geffen Sch Med,Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Germano, PM (reprint author), Univ Calif Los Angeles, CURE, David Geffen Sch Med,Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Bldg 115,Rm 313,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pgermano@ucla.edu FU NIDDK NIH HHS [DK37240] NR 14 TC 5 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-550-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1070 BP 399 EP 404 DI 10.1196/annals.1317.052 PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BEZ57 UT WOS:000240364200056 PM 16888199 ER PT S AU de Gelder, B Meeren, HKM Righart, R van den Stock, J van de Riet, WAC Tamietto, M AF de Gelder, Beatrice Meeren, Hanneke K. M. Righart, Ruthger van den Stock, Jan van de Riet, Wim A. C. Tamietto, Marco BE MartinezConde, S Macknik, SL Martinez, LM Alonso, JM Tse, PU TI Beyond the face: exploring rapid influences of context on face processing SO VISUAL PERCEPTION, PT 2: FUNDAMENTALS OF AWARENESS: MULTI-SENSORY INTEGRATION AND HIGH-ORDER PERCEPTION SE Progress in Brain Research LA English DT Review CT 28th European Conference on Visual Perception CY AUG, 2005 CL Coruna, SPAIN DE fear; body; scene; voice; P1; N170 ID HUMAN EXTRASTRIATE CORTEX; HUMAN VISUAL-CORTEX; HUMAN NEURAL SYSTEM; FACIAL EXPRESSIONS; HUMAN BRAIN; EMOTIONAL EXPRESSIONS; DEVELOPMENTAL PROSOPAGNOSIA; RECOGNITION PROCESSES; CROSSMODAL BINDING; BIOLOGICAL MOTION AB Humans optimize behavior by deriving context-based expectations. Contextual data that are important for survival are extracted rapidly, using coarse information, adaptive decision strategies, and dedicated neural infrastructure. In the field of object perception, the influence of a surrounding context has been a major research theme, and it has generated a large literature. That visual context, as typically provided by natural scenes, facilitates object recognition as has been convincingly demonstrated (Bar, M. (2004) Nat. Rev. Neurosci., 5: 617-629). Just like objects, faces are generally encountered as part of a natural scene. Thus far, the facial expression literature has neglected such context and treats facial expressions as if they stand on their own. This constitutes a major gap in our knowledge. Facial expressions tend to appear in a context of head and body orientations, body movements, posture changes, and other object-related actions with a similar or at least a closely related meaning. For instance, one would expect a frightened face when confronted to an external danger to be at least accompanied by withdrawal movements of head and shoulders. Furthermore, some cues provided by the environment or the context in which a facial expression appears may have a direct relation with the emotion displayed by the face. The brain may even fill in the natural scene context typically associated with the facial expression. Recognition of the facial expression may also profit from processing the vocal emotion as well as the emotional body language that normally accompany it. Here we review the emerging evidence on how the immediate visual and auditory contexts influence the recognition of facial expressions. C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Radboud Univ NIjmegen, FC Donders Ctr Cognit Neuroimaging, NL-6500 HB Nijmegen, Netherlands. Univ Turin, Dept Psychol, Turin, Italy. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. EM B.deGelder@uvt.nl RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 NR 122 TC 60 Z9 60 U1 9 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-51927-6 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2006 VL 155 BP 37 EP 48 DI 10.1016/S0079-6123(06)55003-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BFZ43 UT WOS:000245615200003 PM 17027378 ER PT J AU Grubaugh, AL Monnier, J Magruder, KM Knapp, RG Frueh, BC AF Grubaugh, Anouk L. Monnier, Jeannine Magruder, Kathryn M. Knapp, Rebecca G. Frueh, B. Christopher TI Female veterans seeking medical care at Veterans Affairs primary care clinics: Psychiatric and medical illness burden and service use SO WOMEN & HEALTH LA English DT Article DE primary care; female veterans; PTSD; service use; psychiatric status; medical functioning ID NEUROPSYCHIATRIC INTERVIEW MINI; MENTAL-HEALTH-SERVICES; NATIONAL SAMPLE; WOMEN VETERANS; VA; PREVALENCE; DISORDERS; OUTPATIENTS; SYMPTOMS; ABUSE AB Objective: To examine rates of medical and psychiatric disorders among 187 female veterans recruited at four Veterans Affairs Medical Centers (VAMCs), the recognition of such disorders by VAMC care providers, and the use of relevant medical and mental health services by women both within and outside of the VA setting. Methods: We used a cross-sectional, epidemiological design incorporating self-report measures, structured interviews, and chart reviews to obtain relevant information for analyses. Results: Forty-four percent (43.9%) of women met criteria for at least one psychiatric disorder; 34.0% of these women met criteria for two or more additional psychiatric diagnoses, and concordance rates between interview and chart diagnoses were low. Ninety-five percent (95.2%) of women had a medical condition noted in their charts; 86.6% had two or more additional medical conditions, and a significant number of women had both medical and psychiatric diagnoses. Forty-four percent (43.9%) of women with an identified mental health condition received specialized mental health care by the VA in the past year. Conclusions: Findings from this study suggest that female veterans treated in VAMCs had significant medical and psychiatric problems, and these women might not be getting their health care needs adequately met through the VA health care system. In fight of our findings, we discuss relevant implications and future directions for research. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu; monnierj@musc.edu; magrudkm@musc.edu; knappr@musc.edu; fruehbc@musc.edu NR 28 TC 27 Z9 27 U1 1 U2 3 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2006 VL 43 IS 3 BP 41 EP 62 DI 10.1300/J013v43n03_03 PG 22 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 112RF UT WOS:000242543900003 PM 17194677 ER PT J AU Seelig, MD Gelberg, L Tavrow, P Lee, M Rubenstein, LV AF Seelig, MD Gelberg, L Tavrow, P Lee, M Rubenstein, LV TI Determinants of physician unwillingness to offer medical abortion using mifepristone SO WOMENS HEALTH ISSUES LA English DT Article ID EARLY-PREGNANCY TERMINATION; UNITED-STATES; VAGINAL MISOPROSTOL; RANDOMIZED-TRIAL; SURGICAL ABORTION; 200 MG; INTERNISTS; PROVIDERS; SERVICES AB Purpose. We sought to identify factors associated with contemplating versus not contemplating offering medical abortion with mifepristone among physicians not opposed to it. Methods. We analyzed data from a Kaiser Family Foundation survey of a nationally representative sample of 790 American obstetrician/gynecologists and primary care physicians. Our study sample consisted of 419 physicians who were not personally opposed to medical abortion and could be classified as not actively considering (precontemplation) or actively considering (contemplation) offering mifepristone. We conducted multivariate logistic regression to predict being unlikely to offer mifepristone (i.e., in the precontemplation stage of change). Principal findings. In 2001, 1 year after U.S. Food and Drug Administration (FDA) approval, 5% of physicians surveyed were offering mifepristone. Among the 750 physicians not offering mifepristone, 57% were not opposed. Of those not opposed, 74% reported that they were unlikely to offer mifepristone in the next year (precontemplation) as compared to 23% who might offer it (contemplation). Independent predictors of being in the precontemplation stage were being a primary care versus OB/GYN physician (odds ratio [OR] 3.29, p =.02), being in private versus hospital-based practice (OR 2.40, p =.03), and lacking concerns about FDA regulations (OR 2.06, P =.01) or violence and protests (OR 1.93, p =.03) as barriers to offering mifepristone. Conclusions. For precontemplation-stage physicians, the most efficient strategy for increasing the availability of medical abortion may be to design programs that emphasize clinical benefits and feasibility to stimulate interest in the procedure. For contemplation-stage physicians, the optimum approach may be one that helps to overcome barriers associated with FDA regulations and concerns about violence and protests. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. VA Greater Los Angeles, HSR&D Ctr Excellence, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA USA. RP Seelig, MD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd,Suite 1800, Los Angeles, CA 90024 USA. EM mseelig@mednet.ucla.edu NR 48 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2006 VL 16 IS 1 BP 14 EP 21 DI 10.1016/j.whi.2005.12.001 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 018XW UT WOS:000235799100003 PM 16487920 ER PT J AU Bean-Mayberry, BA Chang, CCH McNeil, MA Scholle, SH AF Bean-Mayberry, BA Chang, CCH McNeil, MA Scholle, SH TI Ensuring high-quality primary care for women: Predictors of success SO WOMENS HEALTH ISSUES LA English DT Article ID PHYSICIAN GENDER; PATIENT SATISFACTION; PREVENTIVE SERVICES; HEALTH CENTERS; DELIVERY; CANCER; ATTRIBUTES; DOCTORS; BREAST AB Background. Provider gender, provider specialty, and clinic setting affect quality of primary care delivery for women, but previous research has not examined these factors in combination. The purpose of this study is to determine whether separate or combined effects of provider gender, availability of gynecologic services from the provider, and women's clinic setting improve patient ratings of primary care. Methods. Women veterans receiving care in women's clinics or traditional primary care at 10 Veteran's Affair (VA) medical centers completed a mailed questionnaire (N = 1321, 61%) rating four validated domains of primary care (preference for provider, communication, coordination, and accumulated knowledge). For each domain, summary scores were calculated and dichotomized into perfect score (maximum score) versus other. Multiple logistic regressions were used to estimate the probability of a perfect score in each domain while controlling for patient characteristics and site. Results. Female provider was significantly associated with perfect ratings for communication and coordination. Providing gynecologic care was significantly associated with perfect ratings for male and female providers. Patients who used a women's clinic and had a female provider who gave gynecologic care had perfect or nearly perfect ratings for preference for provider, communication, and accumulated knowledge. Conclusion. Gynecologic services are linked to patient ratings of primary care separate from and in synergy with the effect of female provider. Male and female providers should consider offering routine gynecologic services or working in coordination with a setting that provides gynecologic services. Health care evaluations should assess scope of services for provider and practice. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Gen Med, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Natl Comm Qual Assurance, Washington, DC USA. RP Bean-Mayberry, BA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151-C, Pittsburgh, PA 15240 USA. EM Bevanne.Bean-Mayberry@med.va.gov NR 32 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2006 VL 16 IS 1 BP 22 EP 29 DI 10.1016/j.whi.2005.12.002 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 018XW UT WOS:000235799100004 PM 16487921 ER PT J AU Salem, RO Cluette-Brown, JE Laposata, M AF Salem, RO Cluette-Brown, JE Laposata, M TI Fatty acid ethyl esters, nonoxidative ethanol metabolites, synthesis, uptake, and hydrolysis by human platelets SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE alcohol; fatty acid; fatty acid ethyl ester; lipid; platelet ID RAT-LIVER MICROSOMES; WHITE BLOOD-CELLS; ALCOHOL-CONSUMPTION; POSTMORTEM MARKERS; ADIPOSE-TISSUE; SYNTHASE; ACYLTRANSFERASE; PURIFICATION; ORGANS AB The consumption of alcohol is known to have both positive and negative effects on the functioning of the cardiovascular system in general, and on platelet function in particular. Fatty acid ethyl esters (FAEEs) are non-oxidative metabolite of ethanol that may mediate the ethanol effect on platelet function leading to either bleeding or clotting. The aim of the current study was to investigate the synthesis, uptake, and hydrolysis of FAEEs by human platelets. Isolated platelets were incubated with ethanol for various times, and FAEE synthesis were measured by gas chromatography mass-spectrometry (GC-MS). In addition, platelets were incubated with C-14-ethyl oleate, and FAEE uptake and hydrolysis were measured. There was significant synthesis of FAEEs by human platelets within 30 min of exposure to ethanol. The major FAEE species formed by human platelets exposed to ethanol were ethyl palmitate and ethyl stearate. FAEE uptake by human platelets showed maximum uptake by 60 s. The majority of FAEEs (50-80%) incorporated into platelets remained intact for up to 10 min. FAEE hydrolysis led to an increase in free fatty acids, with minimal subsequent esterification of the free fatty acids into phospholipids, triglycerides, and cholesterol esters. These studies show that FAEEs, non-oxidative metabolite of ethanol, can be incorporated into, synthesized, and hydrolyzed by human platelets. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Lab Med, Dept Pathol, Boston, MA 02129 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 36 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD DEC 30 PY 2005 VL 1738 IS 1-3 BP 99 EP 104 DI 10.1016/j.bbalip.2005.10.009 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 009CO UT WOS:000235089000013 PM 16325465 ER PT J AU Bailey, JN AF Bailey, JN TI Including endophenotypes as covariates in variance component heritability and linkage analysis SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID TRAITS AB The purpose of these analyses was to determine if incorporating or adjusting for covariates in genetic analyses helped or hindered in genetic analyses, specifically heritability and linkage analyses. To study this question, two types of covariate models were used in the simulated Genetic Analysis Workshop 14 dataset in which the true gene locations are known. All four populations of one replicate were combined for the analyses. The first model included typical covariates of sex and cohort (population) and the second included the typical covariates and also those related endophenotypes that are thought to be associated with the trait (phenotypes A, B, C, D, E, F, G, H, I, J, K, and L). A final best fit model produced in the heritability analyses was used for linkage. Linkage for disease genes D1, D3, and D4 were localized using models with and without the covariates. The use of inclusion of covariates did not appear to have any consistent advantage or disadvantage for the different phenotypes in regards to gene localization or false positive rate. C1 Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Epilepsy Genet Genom Labs, Comprehens Epilepsy Program, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst W Los, Los Angeles, CA USA. RP Bailey, JN (reprint author), Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. EM jbailey@mednet.ucla.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S49 DI 10.1186/1471-2156-6-S1-S49 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400049 PM 16451660 ER PT J AU Hetz, C Vitte, PA Bombrun, A Rostovtseva, TK Montessuit, S Hiver, A Schwarz, MK Church, DJ Korsmeyer, SJ Martinou, JC Antonsson, B AF Hetz, C Vitte, PA Bombrun, A Rostovtseva, TK Montessuit, S Hiver, A Schwarz, MK Church, DJ Korsmeyer, SJ Martinou, JC Antonsson, B TI Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; CYTOCHROME-C RELEASE; CELL-DEATH; PROAPOPTOTIC BAX; FORMING ACTIVITY; ION-CHANNEL; BCL-2; MEMBRANES; VDAC; OLIGOMERIZATION AB Ischemic injuries are associated with several pathological conditions, including stroke and myocardial infarction. Several studies have indicated extensive apoptotic cell death in the infarcted area as well as in the penumbra region of the infarcted tissue. Studies with transgenic animals suggest that the mitochondrion-mediated apoptosis pathway is involved in ischemia-related cell death. This pathway is triggered by activation of pro-apoptotic Bcl-2 family members such as Bax. Here, we have identified and synthesized two low molecular weight compounds that block Bax channel activity. The Bax channel inhibitors prevented cytochrome c release from mitochondria, inhibited the decrease in the mitochondrial membrane potential, and protected cells against apoptosis. The Bax channel inhibitors did not affect the conformational activation of Bax or its translocation and insertion into the mitochondrial membrane in cells undergoing apoptosis. Furthermore, the compounds protected neurons in an animal model of global brain ischemia. The protective effect in the animal model correlated with decreased cytochrome c release in the infarcted area. This is the first demonstration that Bax channel activity is required in apoptosis. C1 Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Chile, Inst Ciencias Biomed, Santiago, Chile. RP Antonsson, B (reprint author), Serono Pharmaceut Res Inst, 14 Chem Aulx, CH-1228 Geneva, Switzerland. EM bruno.antonsson@serono.com RI Hetz, Claudio/I-1900-2013 OI Hetz, Claudio/0000-0001-7724-1767 NR 44 TC 91 Z9 98 U1 0 U2 9 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 DEC 30 PY 2005 VL 280 IS 52 BP 42960 EP 42970 DI 10.1074/jbc.M505843200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996UO UT WOS:000234200800059 PM 16219766 ER PT J AU Iosifescu, DV Papakostas, GI Lyoo, IK Lee, HK Renshaw, PF Alpert, JE Nierenberg, A Fava, M AF Iosifescu, DV Papakostas, GI Lyoo, IK Lee, HK Renshaw, PF Alpert, JE Nierenberg, A Fava, M TI Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I) SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE white matter; hyperintensities; folate; cardiovascular; depression ID AUSTRIAN STROKE PREVENTION; VASCULAR RISK-FACTORS; LATE-LIFE DEPRESSION; SUBCORTICAL HYPERINTENSITIES; SIGNAL HYPERINTENSITIES; HOMOCYSTEINE LEVELS; FOLIC-ACID; FOLLOW-UP; LESIONS; FOLATE AB The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin 1312, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6 +/- 10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin 1312, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2 +/- 9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. Sungkyunkwan Univ, Dept Radiol, Seoul, South Korea. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [K23-MH069629, R01-MH48483, R01-MH58681] NR 56 TC 17 Z9 17 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2005 VL 140 IS 3 BP 291 EP 299 DI 10.1016/j.pscychresns.2005.09.003 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 994EI UT WOS:000234013000008 PM 16298109 ER PT J AU Papakostas, GI Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Alpert, JE Nierenberg, AA Fava, M AF Papakostas, GI Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Alpert, JE Nierenberg, AA Fava, M TI Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II) SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE white matter; hyperintensities; folate; cardiovascular; depression ID SERUM FOLATE; RISK-FACTORS; RESISTANT DEPRESSION; HOMOCYSTEINE LEVELS; CONTINUATION PHASE; ELDERLY-PATIENTS; ANTIDEPRESSANT; FLUOXETINE; VITAMIN-B-12; CHOLESTEROL AB The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range= 0-3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B 12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B 12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Boston, MA 02114 USA. Sungkyunkwan Univ, Dept Radiol, Seoul, South Korea. RP Iosifescu, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [K23 MH069629, R01 MH48483] NR 29 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2005 VL 140 IS 3 BP 301 EP 307 DI 10.1016/j.pscychresns.205.09.001 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 994EI UT WOS:000234013000009 PM 16297603 ER PT J AU Zhai, WG Jeong, H Cui, LB Krainc, D Tjian, R AF Zhai, WG Jeong, H Cui, LB Krainc, D Tjian, R TI In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets SO CELL LA English DT Article ID INTRANUCLEAR INCLUSIONS; POLYGLUTAMINE DISEASE; GENE-EXPRESSION; CAG REPEAT; PROTEIN; SP1; ACTIVATION; BRAIN; TFIIF; DYSREGULATION AB Transcriptional dysregulation has emerged as a potentially important pathogenic mechanism in Huntington's disease, a neurodegenerative disorder associated with polyglutamine expansion in the huntingtin (htt) protein. Here, we report the development of a biochemically defined in vitro transcription assay that is responsive to mutant htt. We demonstrate that both gene-specific activator protein Sp1 and selective components of the core transcription apparatus, including TRID and TFIIF, are direct targets inhibited by mutant htt in a polyglutamine-dependent manner. The RAP30 subunit of TRIF specifically interacts with mutant htt both in vitro and in vivo to interfere with formation of the RAP30-RAP74 native complex. Importantly, overexpression of RAP30 in cultured primary striatal cells protects neurons from mutant htt-induced cellular toxicity and alleviates the transcriptional inhibition of the dopamine D2 receptor gene by mutant htt. Our results suggest a mutant htt-directed repression mechanism involving multiple specific components of the basal transcription apparatus. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodenerat Dis, Charlestown, MA 02129 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Krainc, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM krainc@helix.mgh.harvard.edu; jmlim@uclink4.berkeley.edu FU NCI NIH HHS [CA025417]; NINDS NIH HHS [P01NS045242, R01NS050352] NR 34 TC 111 Z9 111 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 29 PY 2005 VL 123 IS 7 BP 1241 EP 1253 DI 10.1016/j.cell.2005.10.030 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 002AT UT WOS:000234584500013 PM 16377565 ER PT J AU Thurlimann, B Keshaviah, A Coates, AS Mouridsen, H Mauriac, L Forbes, JF Paridaens, R Castiglione-Gertsch, M Gelber, RD Rabaglio, M Smith, I Wardly, A Price, KN Goldhirsch, A AF Thurlimann, B Keshaviah, A Coates, AS Mouridsen, H Mauriac, L Forbes, JF Paridaens, R Castiglione-Gertsch, M Gelber, RD Rabaglio, M Smith, I Wardly, A Price, KN Goldhirsch, A CA BIG 1-98 Collaborative Grp TI A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIAL; AROMATASE INHIBITORS; ADJUVANT TAMOXIFEN; PHASE-III; DRUG-THERAPY; PREVENTION; AROMATIZATION; ANASTROZOLE; COMBINATION; EXEMESTANE AB Background The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. Methods The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. Results A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. Conclusions In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. C1 Int Breast Canc Study Grp Coordinating Ctr, CH-3088 Bern, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Univ Sydney, Sydney, NSW 2006, Australia. Canc Council Australia, Sydney, NSW, Australia. Vejle Hosp, Rigshosp, Danish Breast Canc Grp, Copenhagen, Denmark. Federat Natl Ctr Lutte Canc, Inst Bergonie, Bordeaux, France. Univ Newcastle, Newcastle Mater Hosp, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. Inselspital Bern, CH-3010 Bern, Switzerland. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Royal Marsden Hosp, London SW3 6JJ, England. Royal Marsden Natl Hlth Serv Trust, Surrey, England. Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. Manchester Univ Hosp Trust, Manchester, Lancs, England. European Inst Oncol, Milan, Italy. Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Thurlimann, B (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 56, CH-3088 Bern, Switzerland. EM ibcsg.big198@ibcsg.org OI Wardley, Andrew/0000-0002-9639-0888 NR 38 TC 971 Z9 1003 U1 4 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 29 PY 2005 VL 353 IS 26 BP 2747 EP 2757 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 997LK UT WOS:000234246700006 ER PT J AU August, M Caruso, PA Lahey, ET Faquin, WC Kaban, LB AF August, M Caruso, PA Lahey, ET Faquin, WC Kaban, LB TI Case 40-2005: An 18-year-old man with a one-month history of nontender left mandibular swelling - Odontogenic keratocyst SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TERM FOLLOW-UP; NEEDLE-ASPIRATION BIOPSY; EPITHELIAL-CELL MARKERS; BENIGN CYSTIC NEOPLASM; AGGRESSIVE NATURE; DECOMPRESSION; CYTOKERATIN; EXPRESSION C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP August, M (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 24 TC 2 Z9 3 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 DEC 29 PY 2005 VL 353 IS 26 BP 2798 EP 2805 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 997LK UT WOS:000234246700013 PM 16382067 ER PT J AU Murabito, JM Pencina, MJ Nam, BH D'Agostino, RB Wang, TJ Lloyd-Jones, D Wilson, PWF O'Donnell, CJ AF Murabito, JM Pencina, MJ Nam, BH D'Agostino, RB Wang, TJ Lloyd-Jones, D Wilson, PWF O'Donnell, CJ TI Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; FAMILY-HISTORY; FRAMINGHAM; DEATH; PREVALENCE; TWINS AB Context While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear. Objective To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors. Design, Setting, and Participants The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least I sibling in the study; all were followed up for 8 years. Main Outcome Measures Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence. Results Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% Cl, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% Cl, 1.32-3.00) exceeded that for parental CVD (1.45; 95% Cl, 1.02-2.05). Conclusion Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA USA. Boston Univ, Stat & Consulting Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Div Cardiol, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. Med Univ S Carolina, Dept Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Diabet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med Genet, Charleston, SC 29425 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM murabito@bu.edu RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-25195] NR 27 TC 110 Z9 112 U1 0 U2 2 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 DEC 28 PY 2005 VL 294 IS 24 BP 3117 EP 3123 DI 10.1001/jama.294.24.3117 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 997UL UT WOS:000234274200028 PM 16380592 ER PT J AU Tron, AE Comelli, RN Gonzalez, DH AF Tron, AE Comelli, RN Gonzalez, DH TI Structure of homeodomain-leucine zipper/DNA complexes studied using hydroxyl radical cleavage of DNA and methylation interference SO BIOCHEMISTRY LA English DT Article ID SUNFLOWER HOMEODOMAIN; TRANSCRIPTION FACTORS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; HOMEOBOX GENES; PROTEINS; BINDING; PURIFICATION; SPECIFICITY; CONTACTS AB Homeodomain-leucine zipper (HD-Zip) proteins, unlike most homeodomain proteins, bind a pseudopalindromic DNA sequence as dimers. We have investigated the structure of the DNA complexes formed by two HD-Zip proteins with different nucleotide preferences at the central position of the binding site using footprinting and interference methods. The results indicate that the respective complexes are not symmetric, with the strand bearing a central purine (top strand) showing higher protection around the central region and the bottom strand protected toward the 3' end. Binding to a sequence with a nonpreferred central base pair produces a decrease in protection in either the top or the bottom strand, depending upon the protein. Modeling studies derived from the complex formed by the monomeric Antennapedia homeodomain with DNA indicate that in the HD-Zip/DNA complex the recognition helix of one of the monomers is displaced within the major groove respective to the other one. This monomer seems to lose contacts with a part of the recognition sequence upon binding to the nonpreferred site. The results show that the structure of the complex formed by HD-Zip proteins with DNA is dependent upon both protein intrinsic characteristics and the nucleotides present at the central position of the recognition sequence. C1 Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Catedra Biol Celular & Mol, RA-3000 Santa Fe, Argentina. RP Gonzalez, DH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM dhgonza@fbcb.unl.edu.ar NR 28 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 27 PY 2005 VL 44 IS 51 BP 16796 EP 16803 DI 10.1021/bi0513150 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 999ME UT WOS:000234392700002 PM 16363793 ER PT J AU Allen, AJ Kurlan, RM Gilbert, DL Coffey, BJ Linder, SL Lewis, DW Winner, PK Dunn, DW Dure, LS Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ AF Allen, AJ Kurlan, RM Gilbert, DL Coffey, BJ Linder, SL Lewis, DW Winner, PK Dunn, DW Dure, LS Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ TI Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders SO NEUROLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; RANDOMIZED CONTROLLED-TRIAL; NERVOUS-SYSTEM STIMULANTS; DESIPRAMINE TREATMENT; METHYLPHENIDATE; PLACEBO; GILLES; NOREPINEPHRINE AB Objective: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. Methods: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. Results: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. Conclusions: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/ hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14627 USA. Cincinnati Childrens Hosp, Ctr Med, Dept Pediat, Cincinnati, OH USA. NYU, Ctr Child Study, New York, NY USA. Dallas Pediat Neurol Associates, Dallas, TX USA. Monarch Res Associates, Norfolk, VA USA. Palm Beach Neurol, Premiere Res Inst, W Palm Beach, FL USA. Riley Child & Adolescent Psychiat Clin, Indianapolis, IN USA. Univ Alabama, Div Neurol, Dept Pediat, Birmingham, AL USA. Bancroft NeuroHlth, Cherry Hill, NJ USA. Arizona Family Resource Counseling Ctr, Phoenix, AZ USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02115 USA. RP Allen, AJ (reprint author), Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM allenaj@lilly.com RI Dure, Leon/B-3243-2008; Gilbert, Donald/D-6443-2016 OI Gilbert, Donald/0000-0002-9245-6878 NR 45 TC 122 Z9 126 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 27 PY 2005 VL 65 IS 12 BP 1941 EP 1949 DI 10.1212/01.wnl.0000188869.58300.a7 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 997LH UT WOS:000234246400017 PM 16380617 ER PT J AU Kumar, L Feske, S Rao, A Geha, RS AF Kumar, L Feske, S Rao, A Geha, RS TI A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Lck; proline-rich region ID ADAPTER PROTEIN SLP-76; THYMOCYTE DEVELOPMENT; PROFOUND BLOCK; IMMUNE-SYSTEM; MICE LACKING; ACTIVATION; SELECTION; TYROSINE; DOMAIN; REQUIREMENT AB The adapter SLP-76 is essential for T cell development and function. SLP-76 binds to the src homology 3 domain of Lck in vitro. This interaction depends on amino acids 185-194 of SLP-76. To examine the role of the Lck-binding region of SLP-76 in T cell development and function, SLP-76(-/-) mice were reconstituted with an SLP-76 mutant that lacks amino acids 185-194. Double and single positive thymocytes from reconstituted mice were severely reduced in numbers and exhibited impaired positive selection and increased apoptosis. Peripheral T cells were also reduced in numbers, exhibited impaired phospholipase C-gamma 1 and Erk phosphorylation, and failed to flux calcium, secrete IL-2, and proliferate in response to T cell antigen receptor ligation. Delayed cutaneous hypersensitivity responses and Ab responses to T cell-dependent antigen were severely impaired. These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 1 Blackfan Circle, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [R21 AI054933, R01 AI040127, P01 AI035714, AI-49832, AI-40127, AI-054933] NR 28 TC 8 Z9 9 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 DEC 27 PY 2005 VL 102 IS 52 BP 19063 EP 19068 DI 10.1073/pnas.0509176102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 998WG UT WOS:000234350000051 PM 16354835 ER PT J AU Levine, AA Guan, ZH Barco, A Xu, SQ Kandel, ER Schwartz, JH AF Levine, AA Guan, ZH Barco, A Xu, SQ Kandel, ER Schwartz, JH TI CREB-binding protein controls response to cocaine by acetylating histones at the fosB promoter in the mouse striatum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE addiction; chromatin modulation; memory storage; Rubenstein-Tabi syndrome ID RUBINSTEIN-TAYBI-SYNDROME; LONG-TERM FACILITATION; SUBEROYLANILIDE HYDROXAMIC ACID; GENE-EXPRESSION; NUCLEUS-ACCUMBENS; MESSENGER-RNA; NEURAL BASIS; CBP; TRANSCRIPTION; ADDICTION AB Remodeling chromatin is essential for cAMP-regulated gene expression, necessary not only for development but also for memory storage and other enduring mental states. Histone acetylation and deacetylation mediate long-lasting forms of synaptic plasticity in Aplysia as well as cognition in mice. Here, we show that histone acetylation by the cAMP-response element binding protein (CREB)binding protein (CBP) mediates sensitivity to cocaine by regulating expression of the fosB gene and its splice variant, Delta fosB, a transcription factor previously implicated in addiction. Using the chromatin immunoprecipitation assay with antibodies against histone H4 or CBP, we find that CBP is recruited to the fosB promoter to acetylate histone H4 in response to acute exposure to cocaine. We show that mutant mice that lack one allele of the CBP gene and have normal levels of fosB expression are less sensitive to chronic (10-day) administration of cocaine than are wild-type mice. This decreased sensitivity is correlated with decreased histone acetylation and results in decreased fosB expression and diminished accumulation of Delta fosB. Thus, CBP, which forms part of the promoter complex with CREB, mediates sensitivity to cocaine by acetylating histones. C1 Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, New York State Psychiat Inst, New York, NY 10032 USA. Howard Hughes Med Inst, New York, NY 10032 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. UMH, CSIC, Inst Neurociencias, Alicante 03550, Spain. Columbia Univ, Dept Physiol & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Ctr Mol Therapeut, New York, NY 10032 USA. Columbia Univ, Dept Pharmacol, Coll Phys & Surg, New York, NY 10032 USA. RP Kandel, ER (reprint author), Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. EM erk5@columbia.edu RI Barco, Angel/C-3062-2008 OI Barco, Angel/0000-0002-0653-3751 FU NIMH NIH HHS [MH048850, MH15174, MH60387, R01 MH048850, R01 MH060387, T32 MH015174]; NINDS NIH HHS [NS29255, R01 NS029255] NR 41 TC 142 Z9 150 U1 0 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 DEC 27 PY 2005 VL 102 IS 52 BP 19186 EP 19191 DI 10.1073/pnas.0509735102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 998WG UT WOS:000234350000072 PM 16380431 ER PT J AU Yamamoto, S Lavelle, JM Vagefi, PA Arakawa, H Samelson-Jones, E Moran, S Teranishi, K Kamano, C Fishman, J Awwad, M Neville, DM Shimizu, A Sykes, M Sachs, DH Yamada, K AF Yamamoto, S Lavelle, JM Vagefi, PA Arakawa, H Samelson-Jones, E Moran, S Teranishi, K Kamano, C Fishman, J Awwad, M Neville, DM Shimizu, A Sykes, M Sachs, DH Yamada, K TI Vascularized thymic lobe transplantation in a pig-to-baboon model: A novel strategy for xenogeneic tolerance induction and T-cell reconstitution SO TRANSPLANTATION LA English DT Article DE thymus transplantation; xenotransplantation; pig-to-baboon; tolerance; hDAF pig ID ANTI-GAL ANTIBODY; MINIATURE SWINE; COMPOSITE THYMOKIDNEYS; MISMATCHED BARRIERS; NATURAL ANTIBODIES; NUCLEAR TRANSFER; SELF-TOLERANCE; ADULT THYMUS; IN-VIVO; DONOR AB Background. This laboratory has previously demonstrated the induction of allogeneic tolerance by vascularized thymic lobe (VTL) transplantation in miniature swine. We report here our initial attempt to induce tolerance by VTL transplantation in the clinically relevant, discordant, pig-to-baboon model of xenotransplantation. Methods. Six baboons received xenografts of hDAF VTLs. Four of these baboons also received omental thymic tissue implants. All recipients were treated with an immunosuppressive conditioning regimen that included thymectomy, splenectomy, extracorporeal immunoadsorption of anti-alpha Gal antibodies, and T-cell depletion. Two control baboons received sham operations, of which one also received 5 x 10(8) hDAF porcine thymocytes/kg intravenously. Results. Transplanted VTL grafts supported early thymopoiesis of recipient-type immature thymocytes, and facilitated engraftment of nonvascularized thymic omental implants. Recipients of the VTL grafts demonstrated donor-specific unresponsiveness in MLR assays, development of peripheral CD45RAhigh/CD4 double positive (DP) cells, and positive cytokeratin staining of thymic stroma in the grafts for 2 months following xenotransplantation. The control baboons did not show these markers of thymic reconstitution. The eventual return of Gal natural antibodies led to the destruction of graft epithelial cells and the rejection of all VTL grafts by 3 months posttransplantation. Conclusions. VTL transplantation from hDAF swine to baboons induced early, thymopoiesis in the recipients and donor-specific cellular unresponsiveness in vitro. When coupled with additional strategies aimed at silencing humoral rejection, VTL transplantation may significantly prolong xenograft survival and result in long-term tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge Biotherapeut, Cambridge, MA USA. NIH, Mol Virol Lab, Bethesda, MD 20892 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,CNY 149,9019 13th St, Boston, MA 02129 USA. EM Kaz.yamada@tbrc.mgh.harvard.edu FU PHS HHS [5PO1-A145897, 5PO1-A139755] NR 42 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2005 VL 80 IS 12 BP 1783 EP 1790 DI 10.1097/01.tp.0000184445.70285.4b PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 999BR UT WOS:000234364200024 PM 16378075 ER PT J AU Dor, FJMF Tseng, YL Kuwaki, K Gollackner, B Ramirez, ML Prabharasuth, DD Cina, RA Knosalla, C Nuhn, MG Houser, SL Huang, CA Ko, DSC Cooper, DKC AF Dor, FJMF Tseng, YL Kuwaki, K Gollackner, B Ramirez, ML Prabharasuth, DD Cina, RA Knosalla, C Nuhn, MG Houser, SL Huang, CA Ko, DSC Cooper, DKC TI Immunological unresponsiveness in chimeric miniature swine following MHC-mismatched spleen transplantation SO TRANSPLANTATION LA English DT Article DE chimerism; kidney; pigs; regulatory cells; spleen; suppression; tolerance; transplantation ID HEMATOPOIETIC-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; RENAL-ALLOGRAFT REJECTION; VERSUS-HOST-DISEASE; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; KIDNEY-TRANSPLANTATION; MONOCLONAL-ANTIBODIES; PANCREAS-SPLEEN; MATCHED DONOR AB Background. In rodents, spleen allotransplantation (SpTx) induces tolerance. We investigated the induction of chimerism and donor-specific unresponsiveness following pig SpTx. Methods. Thirteen pigs underwent splenectomy (day 0); all received a blood transfusion. In 11/13 pigs, SpTx was performed across a MHC class I (n=1) or full (n=10) barrier; two control pigs received no SpTx. All pigs were monitored for chimerism, and anti-donor immune responses, including suppressor assays. Four pigs (two asplenic controls and two with SpTx) underwent delayed donor-matched kidney transplantation without immunosuppression. Results. Six of the 11 spleen grafts were lost from rejection (n=5) or splenic vein thrombosis (n= 1), and five remained viable. All 11 SpTx recipients developed multilineage chimerism, but chimerism was rapidly lost if the graft failed. Two control pigs showed < 6% blood chimerism for 4 and 11 days only. Pigs with functioning spleen grafts had multilineage chimerism in blood, thymus and bone marrow for at least 2-6 months, without graft-versus-host disease. These pigs developed in vitro donor-specific hyporesponsiveness and suppression. In 2 pigs tolerant to the spleen graft, donor MHC-matched kidneygrafts survived for > 4 and > 7 months in the absence of exogenous immunosuppression; in two asplenic pigs, kidney grafts were rejected on days 4 and 15. Conclusions. Successful SpTx can result in hematopoietic cell engraftment and in Nitro donor-specific unresponsiveness, enabling prolonged survival of subsequent donor-matched kidney grafts without immunosuppression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Erasmus MC, Dept Surg, Rotterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA 02115 USA. RP Cooper, DKC (reprint author), Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Med Ctr, Biomed Sci Tower E,Room E1550A,200 Lothrop St, Pittsburgh, PA 15261 USA. EM cooperdk@upmc.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1PO1 AI45897] NR 55 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2005 VL 80 IS 12 BP 1791 EP 1804 DI 10.1097/01.tp.0000184625.27076.c8 PG 14 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 999BR UT WOS:000234364200025 PM 16378076 ER PT J AU Kostis, JB Jackson, G Rosen, R Barrett-Connor, E Billups, K Burnett, AL Carson, C Cheitlin, M Debusk, R Fonseca, V Ganz, P Goldstein, I Guay, A Hatzichristou, D Hollander, JE Hutter, A Katz, S Kloner, RA Mittleman, M Montorsi, F Montorsi, P Nehra, A Sadovsky, R Shabsigh, R AF Kostis, JB Jackson, G Rosen, R Barrett-Connor, E Billups, K Burnett, AL Carson, C Cheitlin, M Debusk, R Fonseca, V Ganz, P Goldstein, I Guay, A Hatzichristou, D Hollander, JE Hutter, A Katz, S Kloner, RA Mittleman, M Montorsi, F Montorsi, P Nehra, A Sadovsky, R Shabsigh, R TI Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 2nd Princeton Consensus Conference on Sexual Dysfunction and Cardiac Risk CY JUN 11-12, 2004 CL Princeton, NJ ID LIFE-STYLE CHANGES; ERECTILE-DYSFUNCTION; CARDIOVASCULAR-DISEASE; SILDENAFIL-CITRATE; ENDOTHELIAL DYSFUNCTION; HEART-FAILURE; NITRIC-OXIDE; DOUBLE-BLIND; MEN; TADALAFIL AB Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. St Thomas Hosp, Nashville, TN USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Tulane Univ, Med Ctr, New Orleans, LA 70118 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Lahey Clin Northshore, Ctr Sexual Funct Endocrinol, Peabody, MA USA. Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. Hosp Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. Univ Vita Salute, S Raffaele Hosp, Milan, Italy. Univ Milan, Inst Cardiol, Milan, Italy. Mayo Clin, Rochester, MN USA. SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA. Columbia Univ, Sch Med, New York, NY 10027 USA. RP Kostis, JB (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. EM kostis@umdnj.edu RI Kloner, Robert/B-2971-2012 NR 53 TC 66 Z9 68 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 26 PY 2005 VL 96 IS 12B SU S BP 85M EP 93M DI 10.1016/j.amjcard.2005.03.065 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 001SF UT WOS:000234555900019 PM 16387575 ER PT J AU Farrar, CE Huang, CS Clarke, SG Houser, CR AF Farrar, CE Huang, CS Clarke, SG Houser, CR TI Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE isoaspartyl; neurogenesis; PCMT1; insulin receptor; IGF-I receptor; doublecortin ID CENTRAL-NERVOUS-SYSTEM; FACTOR-I RECEPTOR; INDUCED STATUS EPILEPTICUS; ADULT-RAT HIPPOCAMPUS; INSULIN-RECEPTOR; O-METHYLTRANSFERASE; DAMAGED PROTEINS; IGF-I; ISOASPARTYL PEPTIDES; INDUCED NEUROGENESIS AB Recent studies have demonstrated that mice lacking protein L-isoaspartate (D-aspartate) O-methyltransferase (Pcmt1-/- mice) have alterations in the insulin-like growth factor-I (IGF-I) and insulin receptor pathways within the hippocampal formation as well as other brain regions. However, the cellular localization of these changes and whether the alterations might be associated with an increase in cell number within proliferative regions, such as the dentate gyrus, were unknown. In this study, stereological methods were used to demonstrate that these mice have an increased number of granule cells in the granule cell layer and hilus of the dentate gyrus. The higher number of granule cells was accompanied by a greater number of cells undergoing mitosis in the dentate gyrus, suggesting that an increase in neuronal cell proliferation occurs in this neurogenic zone of adult Pcmt1- / - mice. In support of this, increased doublecortin labeling of immature neurons was detected in the subgranular zone of the dentate gyrus. In addition, double immunofluorescence studies demonstrated that phosphorylated IGF-1/insulin receptors in the subgranular zone were localized on immature neurons, suggesting that the- increased activation of one or both of these receptors in Pcmt1-/- mice could contribute to the growth and survival of these cells. We propose that deficits in the repair of isoaspartyl protein damage leads to alterations in metabolic and growth-receptor pathways, and that this model may be particularly relevant for studies of neurogenesis that is stimulated by cellular damage. C1 Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90095 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 73-235 CHS, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU BLRD VA [I01 BX000404]; NIA NIH HHS [AG18000]; NIGMS NIH HHS [GM26020]; NINDS NIH HHS [NS046524] NR 84 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 26 PY 2005 VL 493 IS 4 BP 524 EP 537 DI 10.1002/cne.20780 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 991QW UT WOS:000233829700004 PM 16304629 ER PT J AU Deshpande, V McKee, GT AF Deshpande, V McKee, GT TI Analysis of atypical urine cytology in a tertiary care center SO CANCER CYTOPATHOLOGY LA English DT Article DE urine; carcinoma; atypical transitional cells; voided urine; cell fragments ID TRANSITIONAL-CELL CARCINOMA; VOIDED URINE; UROTHELIAL CARCINOMA; DIAGNOSTIC-ACCURACY; BLADDER-CARCINOMA; FLOW-CYTOMETRY; FEATURES; CRITERIA; THINPREP(R); SENSITIVITY AB BACKGROUND. Voided urine cytology continues to play a paramount role in the surveillance of transitional cell neoplasms and as a screening modality in certain high-risk situations. Although a significant number of samples are diagnosed as atypical, there is little known about the outcome of these patients. In addition, the significance of transitional cell fragments in voided urine samples is uncertain. The objective of the current study was to evaluate retrospectively a large series of voided urine specimens that were reported as atypical. Standard cytomorphologic parameters Were used with the aim of refining the atypical category. METHODS. The authors studied 201 consecutive voided urine samples from 1995 that were evaluated by liquid-based cytology for the following features: specimen cellularity, the presence and number of cell clusters, and the architecture of the cell fragments. In addition, cells were examined for the following cytologic features: high nuclear-to-cytoplasmic ratios, nuclear membrane irregularities, hyperchromasia, India-ink nuclei, and chromatin pattern. Cytoplasmic features were evaluated but were limited significantly by poor preservation. Only specimens with a biopsy or cystoscopy and/or from patients who were followed for > 5 years were analyzed further. RESULTS. In total, 23.4% of specimens showed transitional cell carcinoma (TCC) on biopsy, including 20 Grade 1 TCCs and 21 Grade 2 TCCs. Specimen cellularity, cluster numbers, nuclear membrane abnormalities, hyperchromasia, and India-ink nuclei were associated significantly with TCC. Twenty-six specimens (18.9%) were associated with renal calculi. CONCLUSIONS. The atypical category contained a significant proportion of low-grade TCCs. Transitional cell clusters in voided urine are relevant clinically. The clinical picture, including the previous history of TCC and the presence of urinary calculi, provides valuable information when evaluating voided urine cytology. These features and careful attention to India-ink nuclei and nuclear membrane abnormalities could help make the "atypical" category a more meaningful group. Cancer (Cancer Cytopathol) 2005;105:468-75. (c) 2005 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 27 TC 35 Z9 36 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2005 VL 105 IS 6 BP 468 EP 475 DI 10.1002/cncr.21317 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 994FF UT WOS:000234015600007 PM 16080177 ER PT J AU Casarett, D Fishman, JM MacMoran, HJ Pickard, A Asch, DA AF Casarett, D Fishman, JM MacMoran, HJ Pickard, A Asch, DA TI Epidemiology and prognosis of coma in daytime television dramas SO BRITISH MEDICAL JOURNAL LA English DT Article ID PERSISTENT VEGETATIVE STATE; SOAP-OPERA; HEAD-INJURY; BREAST-CANCER; BRAIN-DAMAGE; EDUCATION; ATTITUDES; BEHAVIOR; PROGRAM; ADULTS AB Objective To determine how soap operas Portray, and possibly misrepresent, the likelihood of recovery for patients in coma. Design Retrospective cohort study Setting Nine soap operas in the United States reviewed between 1 January 1995 and 15 May 2005. Subjects 64 characters who experienced a period of unconsciousness lasting at least 24 hours. Their final status at the end of the follow-up period was compared with pooled data from a meta-analysis. Results Comas lasted a median of 13 days (interquartile range 7-25 days). Fifty seven (89%) patients recovered fully, five (8%) died, and two (3%) remained in a vegetative state. Mortality for non-traumatic and traumatic coma was significantly lower than would be predicted from the meta-analysis data (non-traumatic 4% v 53%; traumatic 6% v 67%; Fisher's exact test both P < 0.001). On the day that patients regained consciousness, most (49/57; 86%) had no evidence of limited function, cognitive deficit, or residual disability needing rehabilitation. Compared with meta-analysis data, patients in this sample had a much better than expected chance of returning to normal function (non-traumatic 91% v 1%; traumatic 89% 7%; both P < 0.001). Conclusions The portrayal of coma in soap operas is overly optimistic. Although these programmes are presented as fiction, they may contribute to unrealistic expectations of recovery. C1 Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 9 E,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 38 TC 11 Z9 11 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD DEC 24 PY 2005 VL 331 IS 7531 BP 1537 EP 1539 DI 10.1136/bmj.331.7531.1537 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 998WT UT WOS:000234351300025 PM 16373744 ER PT J AU Zhang, F Marcus, WD Goyal, NH Selvaraj, P Springer, TA Zhu, C AF Zhang, F Marcus, WD Goyal, NH Selvaraj, P Springer, TA Zhu, C TI Two-dimensional kinetics regulation of alpha(L)beta(2)-ICAM-1 interaction by conformational changes of the alpha(L)-inserted domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; ADHESION MOLECULE-1 ICAM-1; LIGAND BINDING-KINETICS; RAPID PLATELET-ADHESION; BETA-A DOMAIN; I-DOMAIN; INTEGRIN ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; FORCE SPECTROSCOPY; CRYSTAL-STRUCTURE AB The leukocyte integrin alpha(L)beta(2) mediates cell adhesion and migration during inflammatory and immune responses. Ligand binding of alpha(L)beta(2) is regulated by or induces conformational changes in the inserted ( I) domain. By using a micropipette, we measured the conformational regulation of two-dimensional ( 2D) binding affinity and the kinetics of cell-bound intercellular adhesion molecule-1 interacting with alpha(L)beta(2) or isolated I domain expressed on K562 cells. Locking the I domain into open and intermediate conformations with a disulfide bond increased the affinities by similar to 8000- and similar to 30-fold, respectively, from the locked closed conformation, which has similar affinity as the wild-type I domain. Most surprisingly, the 2D affinity increases were due mostly to the 2D on-rate increases, as the 2D off-rates only decreased by severalfold. The wild-type alpha(L)beta(2), but not its I domain in isolation, could be up-regulated by Mn2+ or Mg2+ to have high affinities and on-rates. Locking the I domain in any of the three conformations abolished the ability of divalent cations to regulate 2D affinity. These results indicate that a downward displacement of the I domain C-terminal helix, induced by conformational changes of other domains of the alpha(L)beta(2), is required for affinity and on-rate up-regulation. C1 Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zhu, C (reprint author), Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. EM cheng.zhu@me.gatech.edu RI Zhu, Cheng/A-5724-2011 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798]; NIAID NIH HHS [AI44902, AI049400, AI38282, R01 AI038282, R01 AI044902, R01 AI049400, R21 AI044902, R29 AI038282, R56 AI038282] NR 55 TC 53 Z9 53 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 2005 VL 280 IS 51 BP 42207 EP 42218 DI 10.1074/jbc.M510407200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XW UT WOS:000233992700049 PM 16234238 ER PT J AU Nathan, DM Cleary, PA Backlund, JYC Genuth, SM Lachin, JM Orchard, TJ Raskin, P Zinman, B AF Nathan, DM Cleary, PA Backlund, JYC Genuth, SM Lachin, JM Orchard, TJ Raskin, P Zinman, B CA DCCT EDIC Stury Res Grp TI Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNRECOGNIZED MYOCARDIAL-INFARCTION; LONG-TERM COMPLICATIONS; CORONARY-ARTERY-DISEASE; HEART-DISEASE; FOLLOW-UP; MELLITUS; MORTALITY; THERAPY; COHORT; TRIAL AB Background: Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease. Methods: The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee. Results: During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P lessthan/equal 0.05) after adjusting for these factors. Conclusions: Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. George Washington Univ, Ctr Biostat, Data Coordinating Ctr, Washington, DC 20052 USA. Med Univ S Carolina, Mol Risk Factors Project, Charleston, SC 29425 USA. RP Nathan, DM (reprint author), DCCT EDIC Res Grp, Box NDIC DCCT, Bethesda, MD 20892 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013; OI orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841 FU NIDDK NIH HHS [N01 DK062204, N01 DK062204-007] NR 35 TC 2169 Z9 2270 U1 13 U2 89 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 22 PY 2005 VL 353 IS 25 BP 2643 EP 2653 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 995IQ UT WOS:000234094400005 PM 16371630 ER PT J AU Papadakis, MA Teherani, A Banach, MA Knettler, TR Rattner, SL Stern, DT Veloski, JJ Hodgson, CS AF Papadakis, MA Teherani, A Banach, MA Knettler, TR Rattner, SL Stern, DT Veloski, JJ Hodgson, CS TI Disciplinary action by medical boards and prior behavior in medical school SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNPROFESSIONAL BEHAVIOR; MEASURING PROFESSIONALISM; STUDENTS; PERFORMANCE; COMPETENCE; EDUCATION AB Background: Evidence supporting professionalism as a critical measure of competence in medical education is limited. In this case-control study, we investigated the association of disciplinary action against practicing physicians with prior unprofessional behavior in medical school. We also examined the specific types of behavior that are most predictive of disciplinary action against practicing physicians with unprofessional behavior in medical school. Methods: The study included 235 graduates of three medical schools who were disciplined by one of 40 state medical boards between 1990 and 2003 (case physicians). The 469 control physicians were matched with the case physicians according to medical school and graduation year. Predictor variables from medical school included the presence or absence of narratives describing unprofessional behavior, grades, standardized-test scores, and demographic characteristics. Narratives were assigned an overall rating for unprofessional behavior. Those that met the threshold for unprofessional behavior were further classified among eight types of behavior and assigned a severity rating (moderate to severe). Results: Disciplinary action by a medical board was strongly associated with prior unprofessional behavior in medical school (odds ratio, 3.0; 95 percent confidence interval, 1.9 to 4.8), for a population attributable risk of disciplinary action of 26 percent. The types of unprofessional behavior most strongly linked with disciplinary action were severe irresponsibility (odds ratio, 8.5; 95 percent confidence interval, 1.8 to 40.1) and severely diminished capacity for self-improvement (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.2). Disciplinary action by a medical board was also associated with low scores on the Medical College Admission Test and poor grades in the first two years of medical school (1 percent and 7 percent population attributable risk, respectively), but the association with these variables was less strong than that with unprofessional behavior. Conclusions: In this case-control study, disciplinary action among practicing physicians by medical boards was strongly associated with unprofessional behavior in medical school. Students with the strongest association were those who were described as irresponsible or as having diminished ability to improve their behavior. Professionalism should have a central role in medical academics and throughout one's medical career. C1 Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Federat State Med Boards, Dallas, TX USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Michigan, Sch Med, Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Colorado, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. RP Papadakis, MA (reprint author), Univ Calif San Francisco, Sch Med, S-245,Box 0454, San Francisco, CA 94143 USA. EM papadakm@medsch.ucsf.edu RI Stern, David/E-8678-2016 OI Stern, David/0000-0001-9278-7303 NR 31 TC 311 Z9 317 U1 2 U2 30 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 DEC 22 PY 2005 VL 353 IS 25 BP 2673 EP 2682 DI 10.1056/NEJMsa052596 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 995IQ UT WOS:000234094400008 PM 16371633 ER PT J AU Ryan, ET Felsenstein, D Aquino, SL Branda, JA Morgan, JG Phillips, J Branda, JA AF Ryan, ET Felsenstein, D Aquino, SL Branda, JA Morgan, JG Phillips, J Branda, JA TI A 63-year-old woman with a positive serologic test for syphilis and persistent eosinophilia - Onchocerca volvulus infection (onchocerciasis) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 22 PY 2005 VL 353 IS 25 BP 2697 EP 2705 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 995IQ UT WOS:000234094400012 PM 16371636 ER PT J AU Parrish, JA AF Parrish, JA TI Immunosuppression, skin cancer, and ultraviolet A radiation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PUVA C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Parrish, JA (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 5 TC 32 Z9 34 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 DEC 22 PY 2005 VL 353 IS 25 BP 2712 EP 2713 DI 10.1056/NEJMcibr054224 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 995IQ UT WOS:000234094400015 PM 16371639 ER PT J AU Kooy, HM Rosenthal, SJ Engelsman, M Mazal, A Slopsema, RL Paganetti, H Flanz, JB AF Kooy, HM Rosenthal, SJ Engelsman, M Mazal, A Slopsema, RL Paganetti, H Flanz, JB TI The prediction of output factors for spread-out proton Bragg peak fields in clinical practice SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION-THERAPY; PHOTON AB The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoe, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Curie, Dept Radiotherapy, Paris, France. RP Kooy, HM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM HKooy@Partners.org FU NCI NIH HHS [5 P01 CA21239-24] NR 14 TC 30 Z9 30 U1 2 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 21 PY 2005 VL 50 IS 24 BP 5847 EP 5856 DI 10.1088/0031-9155/50/24/006 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 000VE UT WOS:000234489700006 PM 16333159 ER PT J AU Craft, D Halabi, T Bortfeld, T AF Craft, D Halabi, T Bortfeld, T TI Exploration of tradeoffs in intensity-modulated radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DOSE DISTRIBUTIONS; NORMAL TISSUE; OPTIMIZATION; TOLERANCE AB The purpose of this study is to calculate Pareto surfaces in multi-criteria radiation treatment planning and to analyse the dependency of the Pareto surfaces on the objective functions used for the volumes of interest. We develop a linear approach that allows us to calculate truly Pareto optimal treatment plans, and we apply it to explore the tradeoff between tumour dose homogeneity and critical structure sparing. We show that for two phantom and two clinical cases, a smooth (as opposed to kinked) Pareto tradeoff curve exists. We find that in the paraspinal cases the Pareto surface is invariant to the response function used on the spinal cord: whether the mean cord dose or the maximum cord dose is used, the Pareto plan database is similar. This is not true for the lung studies, where the choice of objective function on the healthy lung tissue influences the resulting Pareto surface greatly. We conclude that in the special case when the tumour wraps around the organ at risk, e.g. prostate cases and paraspinal cases, the Pareto surface will be largely invariant to the objective function used to model the organ at risk. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 26 TC 59 Z9 59 U1 1 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 21 PY 2005 VL 50 IS 24 BP 5857 EP 5868 DI 10.1088/0031-9155/50/24/007 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 000VE UT WOS:000234489700007 PM 16333160 ER PT J AU Mukamal, KJ Maclure, M Muller, JE Mittleman, MA AF Mukamal, KJ Maclure, M Muller, JE Mittleman, MA TI Binge drinking and mortality after acute myocardial infarction SO CIRCULATION LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE alcohol; epidemiology; myocardial infarction; prognosis ID CORONARY-HEART-DISEASE; VENTRICULAR SYSTOLIC DYSFUNCTION; DENSITY-LIPOPROTEIN CHOLESTEROL; MODERATE ALCOHOL-CONSUMPTION; CARDIOVASCULAR-DISEASE; US ADULTS; RISK; PATTERN; ETHANOL; MORBIDITY AB Background - Moderate drinkers have a lower risk of mortality after myocardial infarction (MI). Although binge drinking has been associated with a higher risk of MI in some studies, its relation to prognosis after MI is uncertain. Methods and Results - In a prospective, inception cohort study conducted at 45 US hospitals, 1935 patients hospitalized with a confirmed MI between 1989 and 1994 underwent detailed personal interviews. Patients reported their usual frequency of binge drinking of beer, wine, and liquor, defined as intake of 3 or more drinks within 1 to 2 hours, and were followed up for mortality for a median of 3.8 years. Of 1919 eligible patients, 250 (94% men) reported binge drinking during the prior year, and a total of 318 patients died during follow-up. Binge drinkers had a 2-fold higher risk of mortality than drinkers who did not binge (hazard ratio, 2.0; 95% confidence interval, 1.3 to 3.0). A comparison of 192 binge drinkers and 192 other patients matched on propensity scores yielded a similar result. The association between binge drinking and total mortality tended to be similar among patients whose usual alcohol intake was light or heavier and for binge drinkers who consumed beer, wine, or liquor. Usual alcohol intake was inversely associated with mortality, but binge drinking completely attenuated this relation. Conclusions - Our results suggest that alcohol consumption may be linked to potential hazards among patients who survive acute MI. Although moderate intake has been associated with lower mortality, binge drinking, even among light drinkers, appears to be associated with 2-fold higher mortality. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave,RO-114, Boston, MA 02215 USA. EM kmukamal@bidmc.harvard.edu FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [R21AA014900] NR 49 TC 74 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3839 EP 3845 DI 10.1161/CIRCULATIONAHA.105.574749 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200006 PM 16365208 ER PT J AU Sabatine, MS Morrow, DA Montalescot, G Dellborg, M Leiva-Pons, JL Keltai, M Murphy, SA McCabe, CH Gibson, CM Cannon, CP Antman, EM Braunwald, E AF Sabatine, MS Morrow, DA Montalescot, G Dellborg, M Leiva-Pons, JL Keltai, M Murphy, SA McCabe, CH Gibson, CM Cannon, CP Antman, EM Braunwald, E CA CLARITY TIMI 28 Investigators TI Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 trial SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE myocardial infarction; heparin; fibrinolysis; angiography ID PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; SEGMENT ELEVATION; REPERFUSION THERAPY; PLASMINOGEN-ACTIVATOR; ANTITHROMBIN THERAPY; INVASIVE STRATEGY; ENOXAPARIN; THROMBOLYSIS; ASPIRIN AB Background - Low-molecular-weight heparin (LMWH) offers pharmacological and practical advantages over unfractionated heparin (UFH). Whether these advantages translate into greater infarct-related artery patency and fewer adverse clinical events in patients with ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy remains under study. Methods and Results - We compared angiographic and clinical outcomes in patients treated with LMWH (n = 1429) versus UFH (n = 1431) in CLARITY-TIMI 28, a randomized trial of clopidogrel versus placebo in STEMI patients aged 18 to 75 years undergoing fibrinolysis. After comprehensive adjustment for baseline characteristics, therapeutic interventions, and a propensity score, treatment with LMWH was associated with a significantly lower rate of a closed infarct-related artery or death or myocardial infarction before angiography(13.5% versus 22.5%, adjusted OR 0.76, P = 0.027). Treatment with LMWH was also associated with a significantly lower rate of cardiovascular death or recurrent myocardial infarction through 30 days (6.9% versus 11.5%, adjusted OR 0.68, P = 0.030). The lower event rates were observed in patients allocated to clopidogrel and in those who underwent percutaneous coronary intervention. Rates of TIMI major bleeding through 30 days (1.6% versus 2.2%, P = 0.27) and intracranial hemorrhage (0.6% versus 0.8%, P = 0.37) were similar in the LMWH and UFH groups. Patients who received both clopidogrel and LMWH, in addition to a standard fibrinolytic and aspirin, had a particularly high rate of infarct-related artery patency (90.9%) and particularly low rates of cardiovascular death (3.2%), recurrent myocardial infarction (3.0%), and major bleeding (1.8%). Conclusions - In patients with STEMI receiving fibrinolytic therapy, use of LMWH with other standard therapies, including clopidogrel and aspirin, is associated with improved angiographic outcomes and lower rates of major adverse cardiovascular events. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. Sahlgrens Univ Hosp, Dept Med, S-41345 Gothenburg, Sweden. Hosp Cent San Luis Potosi, Intervent Cardiol Dept, San Luis Potosi, Mexico. Semmelweis Univ, Hungarian Inst Cardiol, Dept Cardiol, Budapest, Hungary. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 29 TC 45 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3846 EP 3854 DI 10.1161/CIRCULATIONAHA.105.595397 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200007 PM 16291601 ER PT J AU Sabatine, MS Liu, E Morrow, DA Heller, E McCarroll, R Wiegand, R Berriz, GF Roth, FP Gerszten, RE AF Sabatine, MS Liu, E Morrow, DA Heller, E McCarroll, R Wiegand, R Berriz, GF Roth, FP Gerszten, RE TI Metabolomic identification of novel biomarkers of myocardial ischemia SO CIRCULATION LA English DT Article DE exercise; ischemia; metabolism ID AMERICAN-HEART-ASSOCIATION; FUNCTIONAL GENOMICS; METABONOMICS; DIAGNOSIS; CITRATE AB Background - Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia. Methods and Results - Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia ( cases) and 18 of whom did not ( controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases ( adjusted P = 0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy ( P < 0.0001; cross-validated c-statistic = 0.83). Conclusions - We report the novel application of metabolomics to acute myocardial ischemia, in which we identified novel biomarkers of ischemia, and from pathway trend analysis, coordinate changes in groups of functionally related metabolites. C1 Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. CANTATA Pharmaceut, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Room 8307,149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NCI NIH HHS [P20 CA96470-01]; NHLBI NIH HHS [F32 HL68455, R01 HL072872, U01 HL081341] NR 22 TC 254 Z9 273 U1 5 U2 65 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3868 EP 3875 DI 10.1161/CIRCULATIONAHA.105.569137 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200009 PM 16344383 ER PT J AU Madison, JM Nurrish, S Kaplan, JM AF Madison, JM Nurrish, S Kaplan, JM TI UNC-13 interaction with syntaxin is required for synaptic transmission SO CURRENT BIOLOGY LA English DT Article ID MUNC13-1; ELEGANS; FUSION; EXOCYTOSIS; SEROTONIN; PROTEINS; VESICLES; MUTANTS; CALCIUM; POOL AB Neurotransmitter secretion at synapses is controlled by several processes-morphological docking of vesicles at release sites, priming of docked vesicles to make them fusion competent, and calcium-dependent fusion of vesicles with the plasma membrane [1, 2]. In worms, files, and mice, mutants lacking UNC-13 have defects in vesicle priming [3-5]. Current models propose that UNC-13 primes vesicles by stabilizing Syntaxin's "open" conformation by directly interacting with its amino-terminal regulatory domain [6-8]. However, the functional significance of the UNC-13/Syntaxin interaction has not been tested directly. A truncated protein containing the Munc homology domains (MHD1 and MHD2) and the carboxy-terminal C2 domain partially rescued both the behavioral and secretion defects of unc-13 mutants in C. elegans. A double mutation in MHD2 (F1000A/K1002A) disrupts the UNC-13/Syntaxin interaction. The rate of endogenous synaptic events and the amplitude of nerve-evoked excitatory postsynaptic currents (EPSCs) were both significantly reduced in UNC-13S(F1000A/K1002A). However, the pool of primed (i.e., fusion-competent) vesicles was normal. These results suggest that the UNC-13/Syntaxin interaction is conserved in C. elegans and that, contrary to current models, the UNC-13/Syntaxin interaction is required for nerve-evoked vesicle fusion rather than synaptic-vesicle priming. Thus, UNC-13 may regulate multiple steps of the synaptic-vesicle cycle. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. UCL, Dept Pharmacol, Mol Cell Biol Lab, MRC, London WC1E 6BT, England. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM54728]; NINDS NIH HHS [1F32NS10310] NR 20 TC 76 Z9 80 U1 0 U2 3 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 DEC 20 PY 2005 VL 15 IS 24 BP 2236 EP 2242 DI 10.1016/j.cub.2005.10.049 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 998PD UT WOS:000234330300022 PM 16271476 ER PT J AU Mack, JW Hilden, JM Watterson, J Moore, C Turner, B Grier, HE Weeks, JC Wolfe, J AF Mack, JW Hilden, JM Watterson, J Moore, C Turner, B Grier, HE Weeks, JC Wolfe, J TI Parent and physician perspectives on quality of care at the end of life in children with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC PALLIATIVE CARE; FAMILY PERSPECTIVES; SATISFACTION; ONCOLOGISTS; PROGNOSIS AB Purpose: To ascertain parents' and physicians' assessments of quality of end-of-life care for children with cancer and to determine factors associated with high-quality care as perceived by parents and physicians. Methods: A survey was conducted between 1997 and 2001 of 144 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) or Children's Hospitals and Clinics of St Paul and Minneapolis, MN, between 1990 and 1999 (65% of those located and eligible) and 52 pediatric oncologists. Results: In multivariable models, higher parent ratings of physician care were associated with physicians giving clear information about what to expect in the end-of-life period (odds ratio [OR] = 19.90, P = .02), communicating with care and sensitivity (OR = 7.67, P < .01), communicating directly with the child when appropriate (OR = 11.18, P < .01), and preparing the parent for circumstances surrounding the child's death (OR = 4.84, P = .03). Parent reports of the child's pain and suffering were not significant correlates of parental ratings of care (P = .93 and .35, respectively). Oncologists' ratings of care were inversely associated with the parent's report of the child's experience of pain (OR = 0.15, P = .01) and more than 10 hospital days in the last month of life (OR = 0.24, P < .01). Parent-rated communication factors were not correlates of oncologist-rated care. No association was found between parent and physician care ratings (P = .88). Conclusion: For parents of children who die of cancer, doctor-patient communication is the principal determinant of high-quality physician care. In contrast, physicians' care ratings depend on biomedical rather than relational aspects of care. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Cleveland Clin, Dept Pediat Hematol Oncol, Cleveland, OH USA. Childrens Hosp, Cleveland Clin, Dept Pediat Palliat Care, Cleveland, OH USA. Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. Childrens Hosp & Clin, Dept Pediat Hematol Oncol, St Paul, MN 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 AHRQ HHS [T32 HS00063]; NCI NIH HHS [5 K07 CA 096746] NR 26 TC 136 Z9 140 U1 3 U2 12 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 DEC 20 PY 2005 VL 23 IS 36 BP 9155 EP 9161 DI 10.1200/JCO.2005.04.010 PG 7 WC Oncology SC Oncology GA 997FL UT WOS:000234230400020 PM 16172457 ER PT J AU Park, ER Li, FP Liu, Y Emmons, KM Ablin, A Robison, LL Mertens, AC AF Park, ER Li, FP Liu, Y Emmons, KM Ablin, A Robison, LL Mertens, AC TI Health insurance coverage in survivors of childhood cancer: The Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID YOUNG-ADULT SURVIVORS; LONG-TERM SURVIVORS; ADOLESCENT CANCER; 5-YEAR SURVIVORS; LIFE GOALS; LEUKEMIA; COHORT AB Purpose: To examine the prevalence and predictors of health insurance coverage and the difficulties obtaining coverage in a large cohort of childhood cancer survivors. Patients and Methods: This study included 12,358 5-year survivors of childhood cancer and 3,553 sibling controls participating in the Childhood Cancer Survivor Study. Data were collected by surveys distributed in 1994 (baseline) and 2000 (follow-up). Results: At baseline, 83.9% of adult survivors, compared with 88.3% of siblings, had health insurance coverage (P < .01); 6 years later, small but significant survivor-sibling differences remained (88% v 91 %; P < .01). Twenty-nine percent of survivors reported having had difficulties obtaining coverage, compared with only 3% of siblings (P < .01). In multivariate analysis of survivors 18 years of age or older, factors associated with being uninsured included younger age at diagnosis (diagnosis age of 0 to 4 years; odds ratio [OR] = 1.7; 95% Cl, 1.3 to 2.2), male sex (OR = 1.3; 95% Cl, 1.2 to 1.5), age at baseline survey (age 22 to 24 years-, OR = 1.6; 95% Cl, 1.2 to 2.1), lower level of attained education (less than high school, OR = 2.6, 95% Cl, 2.1 to 3.3; high school graduate, OR = 2.1, 95% Cl, 1.8 to 2.5), income less than $20,000 (OR = 5.6, 95% Cl, 4.5 to 7.1), marital status (widowed/divorced/ separated; OR = 1.3; 95% Cl, 1.1 to 1.6), smoking status (current smoker, OR = 2.0, 95% Cl, 1.7 to 2.3; former smoker, OR = 1.4, 95% Cl, 1.2 to 1.8), and treatment that included cranial radiation (OR = 1.3, 95% Cl, 1.0 to 1.6). Conclusion: Compared with siblings, adult survivors of childhood cancer had significantly lower rates of health insurance coverage and more difficulties obtaining coverage. Since lack of coverage likely has serious health and financial implications for this at-risk population, any disparity in availability and quality of coverage is of great concern. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org FU NCI NIH HHS [U24 CA55727] NR 30 TC 56 Z9 57 U1 0 U2 3 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 DEC 20 PY 2005 VL 23 IS 36 BP 9187 EP 9197 DI 10.1200/JCO.2005.01.7418 PG 11 WC Oncology SC Oncology GA 997FL UT WOS:000234230400024 PM 16361621 ER PT J AU Rothenberg, ML LaFleur, B Levy, DE Washington, MK Morgan-Meadows, SL Ramanathan, RK Berlin, JD Benson, AB Coffey, RJ AF Rothenberg, ML LaFleur, B Levy, DE Washington, MK Morgan-Meadows, SL Ramanathan, RK Berlin, JD Benson, AB Coffey, RJ TI Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 12th SPORE Investigators Workshop CY JUL 10-13, 2004 CL Baltimore, MD ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; ZD1839; THERAPY; IRINOTECAN; MUTATIONS; CARCINOMA; ERLOTINIB; CETUXIMAB AB Purpose The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGF alpha). Patients and Methods One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome, Results Median progression-free survival was 1.9 months (95% Cl, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1 %; 95% Cl, 0.01 % to 5%). Median survival was 6.3 months (95% Cl, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. Conclusion Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival. C1 Vanderbilt Univ, Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN 37232 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Wisconsin, Ctr Canc, Madison, WI USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. Northwestern Univ, Lurie Canc Ctr, Chicago, IL 60611 USA. RP Rothenberg, ML (reprint author), Vanderbilt Univ, Ingram Canc Ctr, Div Hematol Oncol, 777 Preston Res Bldg, Nashville, TN 37232 USA. EM mace.rothenberg@vanderbilt.edu FU NCI NIH HHS [K24 CA82301, CA17145, CA21076, CA21115, CA23318, CA39229, CA46413, CA49957, CA66636, P50 CA95103] NR 30 TC 106 Z9 107 U1 0 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 DEC 20 PY 2005 VL 23 IS 36 BP 9265 EP 9274 DI 10.1200/JCO.2005.03.0536 PG 10 WC Oncology SC Oncology GA 997FL UT WOS:000234230400033 PM 16361624 ER PT J AU Armstrong, K Weber, B Ubel, PA Peters, N Holmes, J Schwartz, JS AF Armstrong, K Weber, B Ubel, PA Peters, N Holmes, J Schwartz, JS TI Individualized survival curves improve satisfaction with cancer risk management decisions in women with BRCA1/2 mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HORMONE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; HEREDITARY BREAST-CANCER; SURGICAL ADJUVANT BREAST; ESTROGEN PLUS PROGESTIN; PROPHYLACTIC OOPHORECTOMY; POSTMENOPAUSAL WOMEN; CARRIERS; PREVENTION; TAMOXIFEN AB Purpose Women with BRCA 1/2 mutations are faced with complex decisions about breast and ovarian cancer risk management. This study was conducted to determine the effect of a tailored decision support system (DSS) that provides individualized survival and cancer incidence curves specific to expected outcomes of alternative management strategies. Patients and Methods This was a double-blind, randomized controlled trial of 32 women with BRCA 1/2 mutations. Primary outcome measures were decision satisfaction, cancer anxiety, perceptions of cancer risk given alternative management strategies, and management decisions. Results Twenty-seven women completed a 6-week follow-up. Women in the intervention arm (n = 13) reported significantly higher decision satisfaction at follow-up than women in the control arm (n = 14; adjusted mean difference, 9.7; P < .0005). The effect of the DSS was greater among women with low cancer anxiety at baseline than women with high cancer anxiety at baseline (P = .01 for interaction). However, the DSS did not significantly alter cancer anxiety at follow-up, perceptions of cancer risk given alternative management strategies, or management decisions. Conclusion The presentation of individualized survival and incidence curves for alternative management options improves satisfaction about cancer risk management decisions among women with BRCA1/2 mutations without increasing anxiety or changing management decisions. The benefit of the DSS is greatest among women with relatively low cancer-related anxiety at baseline. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Vet Affairs Hlth Serv Res & Dev, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. RP Armstrong, K (reprint author), 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu NR 40 TC 19 Z9 19 U1 3 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 DEC 20 PY 2005 VL 23 IS 36 BP 9319 EP 9328 DI 10.1200/JCO.2005.06.119 PG 10 WC Oncology SC Oncology GA 997FL UT WOS:000234230400040 PM 16361631 ER PT J AU Fujikawa, SM Chen, IA Szostak, JW AF Fujikawa, SM Chen, IA Szostak, JW TI Shrink-wrap vesicles SO LANGMUIR LA English DT Article ID FATTY-ACID VESICLES; ENERGY-TRANSFER; MAMMALIAN-CELL; MEMBRANE; GROWTH; LIPOSOMES; MODELS; PHOSPHOLIPIDS; NANOPARTICLES; PROTEINS AB We describe a simple approach to the controlled removal of molecules from the membrane of large unilamellar vesicles made of fatty acids. Such vesicles shrink dramatically upon mixing with micelles composed of a mixture of fatty acid and a phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)), as fatty acid molecules leave the vesicle membrane and accumulate within the mixed micelles. Vesicle shrinkage was confirmed by dynamic light scattering, fluorescence recovery after photobleaching of labeled vesicles, and fluorescence resonance energy transfer between lipid dyes incorporated into the vesicle membrane. Most of the encapsulated impermeable solute is retained during shrinkage, becoming concentrated by a factor of at least 50-fold in the final small vesicles. This unprecedented combination of vesicle shrinkage with retention of contents allows for the preparation of small vesicles containing high solute concentrations, and may find applications in liposomal drug delivery. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NIGMS NIH HHS [T32 GM007753-24, T32 GM008313, T32 GM007753, T32 GM008313-19] NR 38 TC 13 Z9 13 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD DEC 20 PY 2005 VL 21 IS 26 BP 12124 EP 12129 DI 10.1021/la052590q PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 994WX UT WOS:000234063000015 PM 16342983 ER PT J AU Zacharakis, G Kambara, H Shih, H Ripoll, J Grimm, J Saeki, Y Weissleder, R Ntziachristos, V AF Zacharakis, G Kambara, H Shih, H Ripoll, J Grimm, J Saeki, Y Weissleder, R Ntziachristos, V TI Volumetric tomography of fluorescent proteins through small animals in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence; whole-body imaging; imaging gene expression; gene transfer; multispectral imaging ID DIFFUSE OPTICAL TOMOGRAPHY; GENE-EXPRESSION; CELLS; ANGIOGENESIS; SYSTEM; TUMORS; MEDIA; MICROSCOPY; EVOLUTION; VECTORS AB Volumetric detection and accurate quantification of fluorescent proteins in entire animals would greatly enhance our ability to monitor biological processes in vivo. Here we present a quantitative tomographic technique for visualization of superficial and deep-seated (> 2-3 mm) fluorescent protein activity in vivo. We demonstrate noninvasive imaging of lung tumor progression in a murine model, as well as imaging of gene delivery using a herpes virus vector. This technology can significantly improve imaging capacity over the current state of the art and should find wide in vivo imaging applications in drug discovery, immunology, and cancer research. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. RP Ntziachristos, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu RI Grimm, Jan/B-1937-2008; Zacharakis, Giannis/A-2544-2014; Ripoll, Jorge/J-8134-2012 OI Zacharakis, Giannis/0000-0002-6438-0773; Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33 CA091807, P50 CA 86355, P50 CA086355, R24 CA 92782, R24 CA092782, R33 CA 91807]; NIBIB NIH HHS [R01 EB 000750-1, R01 EB000750] NR 33 TC 83 Z9 84 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 DEC 20 PY 2005 VL 102 IS 51 BP 18252 EP 18257 DI 10.1073/pnas.0504628102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996LB UT WOS:000234174300004 PM 16344470 ER PT J AU Zhao, JJ Liu, ZN Wang, L Shin, E Loda, MF Roberts, TM AF Zhao, JJ Liu, ZN Wang, L Shin, E Loda, MF Roberts, TM TI The oncogenic properties of mutant p110 alpha and p110 beta phosphatidylinositol 3-kinases in human mammary epithelial cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE orthotopical tumor; PIK3CA; PIK3CB; Akt; oncogene ID P85 REGULATORY SUBUNIT; HUMAN CANCER; PIK3CA GENE; HIGH-FREQUENCY; BREAST-CANCER; T-ANTIGEN; TRANSFORMATION; MUTATIONS; ACTIVATION; PATHWAY AB The PIK3CA gene encoding the p110 alpha subunit of Class 1A phosphaticlylinositol 3-kinases (PI3Ks) is frequently mutated in human tumors. Mutations in the PIK3CB gene encoding p110 beta, the only other widely expressed Class 1A PI3K, have not been reported. We compared the biochemical activity and transforming potential of mutant forms of p110 alpha and p110 beta in a human mammary epithelial cell system. The two most common tumor-derived alleles of p110 alpha, H1047R and E545K, potently activated PI3K signaling. Human mammary epithelial cells expressing these alleles grew efficiently in soft agar and as orthotopic tumors in nude mice. We also examined a third class of mutations in p110a, those in the p85-binding domain. A representative tumor-derived p85-binding-domain mutant R38H showed modestly reduced p85 binding and weakly activated PI3K/Akt signaling. In contrast, a deletion mutant lacking the entire p85-binding domain efficiently activated PI3K signaling. When we constructed in p110 beta a mutation homologous to the E545K allele of p110a,the resulting p110 beta mutant was only weakly activated and allowed minimal soft-agar growth. However, a gene fusion of p110 beta with the membrane anchor from c-Src was highly active and transforming in both soft-agar and orthotopic nude mouse assays. Thus, although introduction of activating mutations from p110 alpha at the corresponding sites in p110 beta failed to render the enzyme oncogenic in human cells, the possibility remains that other mutations might activate the beta isoform. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu; thomas_roberts@dfci.harvard.edu FU NCI NIH HHS [R01 CA030002, 5P50CA090381-05, CA089021, CA30002, P01 CA050661, P01 CA089021, P01-CA50661, P50 CA090381, R37 CA030002] NR 27 TC 192 Z9 198 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 DEC 20 PY 2005 VL 102 IS 51 BP 18443 EP 18448 DI 10.1073/pnas.0508988102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996LB UT WOS:000234174300037 PM 16339315 ER PT J AU Merki, E Zamora, L Raya, A Kawakami, Y Wang, JM Zhang, XX Burch, J Kubalak, SW Kaliman, P Belmonte, JCI Chien, KR Ruiz-Lozano, P AF Merki, E Zamora, L Raya, A Kawakami, Y Wang, JM Zhang, XX Burch, J Kubalak, SW Kaliman, P Belmonte, JCI Chien, KR Ruiz-Lozano, P TI Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE coronary vessels; epicardium; retinoids; wnt; FGF ID RXR-ALPHA; MESENCHYMAL TRANSFORMATION; BETA-CATENIN; CARDIAC MORPHOGENESIS; HEART MORPHOGENESIS; THYROID-HORMONE; GENE ACTIVITY; AVIAN HEART; AORTIC SAC; IN-VIVO AB Vitamin A signals play critical roles during embryonic development. in particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXR alpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXR alpha signaling in this process are unclear, because a myocardium-restricted RXR alpha mutation does not perturb heart morphogenesis. Here, we analyze a series of tissue-restricted mutations of the RXR alpha gene in the cardiac neural crest, endothelial, and epicardial lineages, and we show that RXR alpha signaling in the epicardium is required for proper cardiac morphogenesis. Moreover, we detect an additional phenotype of defective coronary arteriogenesis associated with RXR alpha deficiency and identify a retinoid-dependent Wnt signaling pathway that cooperates in epicardial epithelial-to-mesenchymal transformation. C1 Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Salk Inst, Gene Express Lab, San Diego, CA 92186 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Med Univ S Carolina, Cardiovasc Dev Biol Ctr, Charleston, SC 29425 USA. Univ Barcelona, Dept Bioquim & Biol Mol, Barcelona 08028, Spain. Burnham Inst, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, MGH Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Chien, KR (reprint author), Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. EM kchien@partners.org; plozano@burnham.org RI Raya, Angel/E-6205-2010 OI Raya, Angel/0000-0003-2189-9775 FU NHLBI NIH HHS [R01 HL063714-04, R01 HL063714] NR 43 TC 181 Z9 186 U1 1 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 DEC 20 PY 2005 VL 102 IS 51 BP 18455 EP 18460 DI 10.1073/pnas.0504343102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996LB UT WOS:000234174300039 PM 16352730 ER PT J AU Gelder, BC Morris, JS Dolan, RJ AF Gelder, BC Morris, JS Dolan, RJ TI Unconscious fear influences emotional awareness of faces and voices SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amygdala; blindsight; affective blindsight; consciousness; nonconscious processes ID FACIAL EXPRESSIONS MODULATE; HUMAN AMYGDALA; VISUAL EXTINCTION; PREFRONTAL CORTEX; STRIATE CORTEX; STIMULI; RECOGNITION; PERCEPTION; ACTIVATION; RESPONSES AB Nonconscious recognition of facial expressions opens an intriguing possibility that two emotions can be present together in one brain with unconsciously and consciously perceived inputs interacting. We investigated this interaction in three experiments by using a hemianope patient with residual nonconscious vision. During simultaneous presentation of facial expressions to the intact and the blind field, we measured interactions between conscious and nonconsciously recognized images. Fear-specific congruence effects were expressed as enhanced neuronal activity in fusiform gyrus, annygdala, and pulvinar. Nonconscious facial expressions also influenced processing of consciously recognized emotional voices. Emotional congruency between visual and an auditory input enhances activity in amygdala and superior colliculus for blind, relative to intact, field presentation of faces. Our findings indicate that recognition of fear is mandatory and independent of awareness. Most importantly, unconscious fear recognition remains robust even in the light of a concurrent incongruent happy facial expression or an emotional voice of which the observer is aware. C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Inst Child Hlth, Behav & Brain Sci Unit, London WC1N 1EH, England. Inst Neurol, Wellcome Dept Cognit Neurol, London WC1N 3BG, England. RP Gelder, BC (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Bldg 36,Room 409, Boston, MA 02129 USA. EM degelder@uvt.nl RI Frank, David/E-8213-2012; OI Dolan, Ray/0000-0001-9356-761X NR 53 TC 3 Z9 4 U1 3 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 DEC 20 PY 2005 VL 102 IS 51 BP 18682 EP 18687 DI 10.1073/pnas.0509179102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996LB UT WOS:000234174300078 ER PT J AU Song, B Diaz-Griffero, F Park, DH Rogers, T Stremlau, M Sodroski, J AF Song, B Diaz-Griffero, F Park, DH Rogers, T Stremlau, M Sodroski, J TI TRIM5 alpha association with cytoplasmic bodies is not required for antiretroviral activity SO VIROLOGY LA English DT Article DE retrovirus; restriction; cytoplasmic bodies; cytoplasmic speckles; geldanamycin; TRIM5 alpha; tripartite motif; HIV-1 ID BROAD-HOST-RANGE; MONKEY TRIM5-ALPHA; OLD-WORLD; RESTRICTION; VIRUS; REPLICATION; AGGRESOMES; INFECTION; PROTEINS; DOMAIN AB The tripartite motif (TRIM) protein, TRIN15 alpha, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5 alpha. In addition to diffuse cytoplasmic staining, the TRIM5 alpha proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5 alpha from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5 alpha proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5 alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5 alpha fusion proteins indicated that no TRIM5a domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5 alpha. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI28691, AI063987] NR 27 TC 43 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2005 VL 343 IS 2 BP 201 EP 211 DI 10.1016/j.virol.2005.08.019 PG 11 WC Virology SC Virology GA 997QQ UT WOS:000234262100006 PM 16183097 ER PT J AU Kim, R Demichelis, F Tang, J Riva, A Shen, RL Gibbs, DF Mahavishno, V Chinnaiyan, AM Rubin, MA AF Kim, R Demichelis, F Tang, J Riva, A Shen, RL Gibbs, DF Mahavishno, V Chinnaiyan, AM Rubin, MA TI Internet-based profiler system as integrative framework to support translational research SO BMC BIOINFORMATICS LA English DT Article ID PROSTATE-CANCER PROGRESSION; METHYLACYL-COA RACEMASE; TISSUE MICROARRAY DATA; RELATIONAL DATABASE; PROTEIN EXPRESSION; BIOMARKER; PROLIFERATION; PRECURSOR; PROGRAM; MARKER AB Background: Translational research requires taking basic science observations and developing them into clinically useful tests and therapeutics. We have developed a process to develop molecular biomarkers for diagnosis and prognosis by integrating tissue microarray (TMA) technology and an internet-database tool, Profiler. TMA technology allows investigators to study hundreds of patient samples on a single glass slide resulting in the conservation of tissue and the reduction in inter-experimental variability. The Profiler system allows investigator to reliably track, store, and evaluate TMA experiments. Here within we describe the process that has evolved through an empirical basis over the past 5 years at two academic institutions. Results: The generic design of this system makes it compatible with multiple organ system (e.g., prostate, breast, lung, renal, and hematopoietic system,). Studies and folders are restricted to authorized users as required. Over the past 5 years, investigators at 2 academic institutions have scanned 656 TMA experiments and collected 63,311 digital images of these tissue samples. 68 pathologists from 12 major user groups have accessed the system. Two groups directly link clinical data from over 500 patients for immediate access and the remaining groups choose to maintain clinical and pathology data on separate systems. Profiler currently has 170 K data points such as staining intensity, tumor grade, and nuclear size. Due to the relational database structure, analysis can be easily performed on single or multiple TMA experimental results. The TMA module of Profiler can maintain images acquired from multiple systems. Conclusion: We have developed a robust process to develop molecular biomarkers using TMA technology and an internet-based database system to track all steps of this process. This system is extendable to other types of molecular data as separate modules and is freely available to academic institutions for licensing. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. RP Rubin, MA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM rkim7@partners.org; fdemichelis@partners.org; jtang2@partners.org; alb@chip.org; rlshen@med.umich.edu; dgibbs@med.umich.edu; vmahavis@med.umich.edu; arul@umich.edu; marubin@partners.org FU NCI NIH HHS [CA 97063, P50CA69568, P50 CA069568, R01 CA097063]; NIA NIH HHS [R01 AG021404, R01AG21404] NR 33 TC 8 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 19 PY 2005 VL 6 AR 304 DI 10.1186/1471-2105-6-304 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 005XU UT WOS:000234860500001 PM 16364175 ER PT J AU Irie, HY Pearline, RV Grueneberg, D Hsia, M Ravichandran, P Kothari, N Natesan, S Brugge, JS AF Irie, HY Pearline, RV Grueneberg, D Hsia, M Ravichandran, P Kothari, N Natesan, S Brugge, JS TI Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROTEIN-KINASE-B; FACTOR-I RECEPTOR; GROWTH-FACTOR-BETA; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; INSULIN; ACTIVATION; INVASION; CANCER AB The Akt family of kinases are activated by growth factors and regulate pleiotropic cellular activities. In this study, we provide evidence for isoform-specific positive and negative roles for Akt1 and -2 in regulating growth factor-stimulated phenotypes in breast epithelial cells. Insulin-like growth factor-I receptor (IGF-IR) hyperstimulation induced hyperproliferation and antiapoptotic activities that were reversed by Akt2 down-regulation. In contrast, Akt1 down-regulation in IGF-IR-stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial-mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. The phenotypic effects of Akt1 down-regulation were accompanied by enhanced extracellular signal-related kinase (ERK) activation, which contributed to the induction of migration and EMT. Interestingly, down-regulation of Akt2 suppressed the EMT-like morphological conversion induced by Akt1 down-regulation in IGF-IR-overexpressing cells and inhibited migration in EGF-stimulated cells. These results highlight the distinct functions of Akt isoforms in regulating growth factor-stimulated EMT and cell migration, as well as the importance of Akt1 in cross-regulating the ERK signaling pathway. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Sanofi Aventis Pharmaceut, Cambridge Genom Ctr, Cambridge, MA 02139 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu FU NCI NIH HHS [R01 CA105134, CA105134, CA80111, P01 CA080111] NR 45 TC 350 Z9 361 U1 2 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 19 PY 2005 VL 171 IS 6 BP 1023 EP 1034 DI 10.1083/jcb.200505087 PG 12 WC Cell Biology SC Cell Biology GA 994TI UT WOS:000234053700014 PM 16365168 ER PT J AU Alon, R Feigelson, SW Manevich, E Rose, DM Schmitz, J Overby, DR Winter, E Grabovsky, V Shinder, V Matthews, BD Sokolovsky-Eisenberg, M Ingber, DE Benoit, M Ginsberg, MH AF Alon, R Feigelson, SW Manevich, E Rose, DM Schmitz, J Overby, DR Winter, E Grabovsky, V Shinder, V Matthews, BD Sokolovsky-Eisenberg, M Ingber, DE Benoit, M Ginsberg, MH TI alpha(4)beta(1)-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha(4)-cytoplasmic domain SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ALPHA(4) CYTOPLASMIC DOMAIN; CELL-ADHESION; L-SELECTIN; LEUKOCYTE ADHESION; SHEAR-FLOW; INTEGRIN ACTIVATION; AVIDITY REGULATION; LYMPHOCYTE ARREST; T-CELLS; BINDING AB The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which alpha(4)-integrin adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the alpha(4) tail that disrupts paxillin binding, alpha(4)(Y991A), reduced talin association to the alpha(4)beta(1) heterodimer, impaired integrin anchorage to the cytoskeleton, and suppressed alpha(4)beta(1)-dependent capture and adhesion strengthening of Jurkat T cells to VCAM-1 under shear stress. The mutant retained intrinsic avidity to soluble or bead-immobilized VCAM-1, supported normal cell spreading at short-lived contacts, had normal alpha(4)-microvillar distribution, and responded to inside-out signals. This is the first demonstration that cytoskeletal anchorage of an integrin enhances the mechanical stability of its adhesive bonds under strain and, thereby, promotes its ability to mediate leukocyte adhesion under physiological shear stress conditions. C1 Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Munich, Ctr Nano Sci, D-80799 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Dept Surg, Boston, MA 02115 USA. RP Alon, R (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. EM ronen.alon@weizmann.ac.il RI Overby, Darryl/G-1520-2011 OI Overby, Darryl/0000-0001-9894-7515 FU NCI NIH HHS [CA45548, P01 CA045548]; NHLBI NIH HHS [HL57009]; NIAMS NIH HHS [AR27214, P30 AR047360, P30AR47360, R01 AR027214, R37 AR027214] NR 46 TC 70 Z9 72 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 19 PY 2005 VL 171 IS 6 BP 1073 EP 1084 DI 10.1083/jcb.200503155 PG 12 WC Cell Biology SC Cell Biology GA 994TI UT WOS:000234053700018 PM 16365170 ER PT J AU Flores-Villanueva, PO Ruiz-Morales, JA Song, CH Flores, LM Jo, EK Montano, M Barnes, PF Selman, M Granados, J AF Flores-Villanueva, PO Ruiz-Morales, JA Song, CH Flores, LM Jo, EK Montano, M Barnes, PF Selman, M Granados, J TI A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERFERON-GAMMA GENE; MYCOBACTERIUM-TUBERCULOSIS; NRAMP1 GENE; POPULATION STRATIFICATION; IL-12 PRODUCTION; HUMAN-DISEASE; EXPRESSION; IMMUNITY; MCP-1 AB We examined the distribution of single nucleotide polymorphisms ( SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein-1 alpha genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti-MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis - stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis - stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis. C1 Univ Texas Hlth Ctr, Ctr Biomed Res, Tyler, TX 75708 USA. Chungnam Natl Univ, Coll Med, Dept Microbiol, Taejon 301747, South Korea. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Mexican Inst Resp Dis, Mexico City 14080, DF, Mexico. Mexican Natl Inst Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico. RP Flores-Villanueva, PO (reprint author), Univ Texas Hlth Ctr, Ctr Biomed Res, Tyler, TX 75708 USA. EM pedro.flores@UTHCT.edu FU NHLBI NIH HHS [HL04095-04, K30 HL004095, R21 HL072177, R21 HL72177] NR 59 TC 166 Z9 178 U1 1 U2 8 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 DEC 19 PY 2005 VL 202 IS 12 BP 1649 EP 1658 DI 10.1084/jem20050216 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 994TH UT WOS:000234053600006 PM 16352737 ER PT J AU Siddiq, A Ayoub, IA Chavez, JC Aminova, L Shah, S LaManna, JC Patton, SM Connor, JR Cherny, RA Volitakis, I Bush, AI Langsetmo, I Seeley, T Gunzler, V Ratan, RR AF Siddiq, A Ayoub, IA Chavez, JC Aminova, L Shah, S LaManna, JC Patton, SM Connor, JR Cherny, RA Volitakis, I Bush, AI Langsetmo, I Seeley, T Gunzler, V Ratan, RR TI Hypoxia-inducible factor prolyl 4-hydroxylase inhibition - A target for neuroprotection in the central nervous system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBRAL ISCHEMIC ACIDOSIS; PARKINSONS-DISEASE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; HIF-ALPHA; IN-VITRO; PROLINE HYDROXYLATION; TRANSFERRIN RECEPTOR; FRIEDREICHS-ATAXIA; SUBSTANTIA-NIGRA AB Hypoxia-inducible factor (HIF) prolyl 4-hydroxylases are a family of iron- and 2-oxoglutarate-dependent dioxygenases that negatively regulate the stability of several proteins that have established roles in adaptation to hypoxic or oxidative stress. These proteins include the transcriptional activators HIF-1 alpha and HIF-2 alpha. The ability of the inhibitors of HIF prolyl 4-hydroxylases to stabilize proteins involved in adaptation in neurons and to prevent neuronal injury remains unclear. We reported that structurally diverse low molecular weight or peptide inhibitors of the HIF prolyl 4-hydroxylases stabilize HIF-1 alpha and up-regulate HIF-dependent target genes (e.g. enolase, p21(waf1/cip1), vascular endothelial growth factor, or erythropoietin) in embryonic cortical neurons in vitro or in adult rat brains in vivo. We also showed that structurally diverse HIF prolyl 4-hydroxylase inhibitors prevent oxidative death in vitro and ischemic injury in vivo. Taken together these findings identified low molecular weight and peptide HIF prolyl 4-hydroxylase inhibitors as novel neurological therapeutics for stroke as well as other diseases associated with oxidative stress. C1 Burke Cornell Med Res Inst, White Plains, NY 10605 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Case Western Reserve Univ, Dept Anat & Neurol, Cleveland, OH 44106 USA. Penn State Coll Med, George M Leader Family Lab Alzheimer Dis Res, Dept Neurosurg, Hershey, PA 17033 USA. Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Lab Oxidat Biol, Dept Psychiat,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Fibrogen Inc, San Francisco, CA 94080 USA. RP Ratan, RR (reprint author), Burke Cornell Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA. EM rrr2001@cornell.med.edu RI LaManna, Joseph/C-3347-2012; Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU NINDS NIH HHS [F32 NS046239, NS39170, NS40591, NS46239, R01 NS039170-02, R01 NS040591] NR 59 TC 196 Z9 201 U1 1 U2 12 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 DEC 16 PY 2005 VL 280 IS 50 BP 41732 EP 41743 DI 10.1074/jbc.M504963200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992EJ UT WOS:000233866900075 PM 16227210 ER PT J AU Rodriguez, JD Royall, D Daum, LT Kagan-Hallet, K Chambers, JP AF Rodriguez, JD Royall, D Daum, LT Kagan-Hallet, K Chambers, JP TI Amplification of Herpes simplex type 1 and Human Herpes type 5 viral DNA from formalin-fixed Alzheimer brain tissue SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's; herpes; formalin-fixed; brain ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; VIRUS TYPE-1; DISEASE BRAINS; FORMALDEHYDE; FIXATIVES; PCR AB It is known that nucleic acids from formalin-fixed tissues are not nearly as good templates for DNA amplification as those extracted from fresh tissues. However, specimens stored in most pathologic archives are initially fixed in formalin. The possibility of an infectious etiology of several diseases including Alzheimer's underscores the usefulness of archived tissue in assessing the association of infectious agents with specific pathology. In this report, we describe in detail a method resulting in robust amplification of HSV1 and Human Herpes type (HHV) 5 viral DNA targets using formalin-fixed Alzheimer brain frontal and temporal tissue as source of amplification template. Herpes simplex type 2 viral DNA was not detected in the limited samples examined in this study. Amplicons were verified by sequence analysis. Brain tissue stored in formalin longer than 1 year prior to post-formalin-fixation analysis gave rise to significantly shorter amplicons consistent with the observation that template DNA integrity decreases significantly with increasing time of storage in formalin. Thus, this report should be useful in PCR-based investigations assessing the regional presence of viral DNAs in formalin-fixed brain tissue. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Dept Biol, San Antonio, TX 78249 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Pathol, San Antonio, TX 78229 USA. RP Chambers, JP (reprint author), Univ Texas, Dept Biol, 6900 N Loop 1604 W,SB Rm 1-01-28, San Antonio, TX 78249 USA. EM james.chambers@utsa.edu FU NIGMS NIH HHS [GM 00819] NR 15 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 16 PY 2005 VL 390 IS 1 BP 37 EP 41 DI 10.1016/j.neulet.2005.07.052 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 970RN UT WOS:000232327400008 PM 16118038 ER PT J AU Clearfield, M Downs, JR Lee, M Langendorfer, A McConathy, W Gotto, AM AF Clearfield, M Downs, JR Lee, M Langendorfer, A McConathy, W Gotto, AM TI Implications from the Air Force/Texas Coronary Atherosclerosis Prevention Study for the Adult Treatment Panel III guidelines SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; METABOLIC SYNDROME; APOLIPOPROTEIN-B; FOLLOW-UP; EVENTS; RISK; AFCAPS/TEXCAPS; ASSOCIATIONS; PREDICTOR; DISEASE AB The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) first reported its results in 1998, before the 2001 publication of the National Cholesterol Education Program-Adult Treatment Panel III guidelines (NCEP-ATP III) and 2004 update. Our objective was to investigate the impact of these guidelines on the AFCAPS/TexCAPS cohort. The main outcome measures were the event rates of first acute major coronary events (AMCEs), which were reduced 39% by lovastatin (95% confidence interval [CI] 21% to 53%, p <0.001) in the 65% of the cohort eligible for drug therapy and by 34% (95% CI -9% to 60%, p = 0.108) in the remaining 35% for whom drug therapy was considered optional. The evaluation of other guideline components included a 44% (95% CI 27% to 58%, p <0.001) reduction in AMCEs in subjects with baseline high-density lipoprotein cholesterol <40 mg/dl and a 41% (95% CI 19% to 57%) reduction in AMCEs in subjects with the metabolic syndrome. In the recent update, patients who had a moderately high risk of coronary heart disease and a baseline low-density lipoprotein cholesterol level of 100 to 130 mg/dl could be considered for therapy with a medication to lower the low-density lipoprotein cholesterol level to <100 mg/dl. A total of 334 subjects (5.1%) were in this group, in whom lovastatin reduced the risk of AMCEs by 68% (95% CI 12% to 88%, p = 0.027). However, 21% of the AMCEs were missed by the guidelines. Metabolic syndrome was noted in 48% of these subjects and may help define those in whom treatment with a medication is now considered optional. In conclusion, the ability of the ATP III guidelines and its update has markedly improved our ability to define coronary heart disease risk; however, other components of the guidelines, such as non-high-density lipoprotein cholesterol and the optional low-density lipoprotein cholesterol target goal of < 100 mg/dl, still require additional evaluation. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ N Texas, Hlth Sci Ctr, Dept Internal Med, Ft Worth, TX 76107 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Merck Res Labs, Rahway, NJ USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP Clearfield, M (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Internal Med, Ft Worth, TX 76107 USA. EM mclearfi@hsc.unt.edu NR 18 TC 18 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2005 VL 96 IS 12 BP 1674 EP 1680 DI 10.1016/j.amjcard.2005.07.079 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 997BR UT WOS:000234220500012 PM 16360356 ER PT J AU Mukherjee, D Evangelista, A Nienaber, CA Sechtem, U Suzuki, T Trimarchi, S Llovet, A Myrmel, T O'Gara, PT Fang, JM Cooper, JV Oh, JK Januzzi, JL Hutchison, S Fattori, R Pape, LA Isselbacher, EM Eagle, KA AF Mukherjee, D Evangelista, A Nienaber, CA Sechtem, U Suzuki, T Trimarchi, S Llovet, A Myrmel, T O'Gara, PT Fang, JM Cooper, JV Oh, JK Januzzi, JL Hutchison, S Fattori, R Pape, LA Isselbacher, EM Eagle, KA TI Implications of periaortic hematoma in patients with acute aortic dissection (from the International Registry of Acute Aortic Dissection) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB The clinical profiles, presentation, and outcomes of patients with acute aortic dissections and associated periaortic hematomas on aortic imaging have not been described in a large cohort. This study sought to assess the prognostic implications of periaortic hematomas in patients with aortic dissections and to identify factors associated with in-hospital mortality in patients with periaortic hematomas. The study population was 971 patients with acute aortic dissections enrolled in the International Registry of Acute Aortic Dissection with available imaging data on presentation with the presence or absence of periaortic hematomas. Patients with periaortic hematomas (n=227, 23.4%) were more likely to be women, to have a history of hypertension and atherosclerosis, and to present early to the hospital. At presentation, they had greater frequencies of shock, cardiac tamponade, coma, and/or altered consciousness. Clinical outcomes were significantly worse in patients with periaortic hematomas, including significantly greater mortality (33% vs 20.3%, p<0.001). A multivariate model demonstrated periaortic hematomas to be an independent predictor of mortality in patients with aortic dissections (odds ratio 1.71, 95% confidence interval 1.15 to 2.54, p=0.007). In conclusion, this study provides insight into the profiles, presentation, and outcomes of patients with periaortic hematomas and acute aortic dissections. The early identification and aggressive management of patients with periaortic hematomas may potentially improve clinical outcomes. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA. Hosp Gen Univ Vall Hebron, Barcelona, Spain. Univ Rostock, Rostock, Germany. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Tokyo, Tokyo, Japan. Ist Policlin San Donato, San Donato Milanese, Italy. Hosp Univ 12 Octubre, Madrid, Spain. Univ Tromso Hosp, N-9012 Tromso, Norway. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Hosp S Orsola, Bologna, Italy. Univ Massachusetts Hosp, Worcester, MA USA. RP Mukherjee, D (reprint author), Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA. EM mukherjee@uky.edu RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; Mukherjee, Debabrata/0000-0002-5131-3694 NR 5 TC 16 Z9 16 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2005 VL 96 IS 12 BP 1734 EP 1738 DI 10.1016/j.amjcard.2005.07.098 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 997BR UT WOS:000234220500023 PM 16360367 ER PT J AU Goodman, FDC Glassman, P AF Goodman, FDC Glassman, P TI Evaluating potentially aberrant outpatient prescriptions for extended-release oxycodone SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Vet Hlth Adm, Hines, IL 60141 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Goodman, FDC (reprint author), Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Vet Hlth Adm, 1st Ave & Cermak Rd,Bldg 17,Room 139, Hines, IL 60141 USA. EM francine.goodman@med.va.gov NR 12 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD DEC 15 PY 2005 VL 62 IS 24 BP 2604 EP 2608 DI 10.2146/ajhp040618 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995QX UT WOS:000234120000006 PM 16333058 ER PT J AU Lin, AE Pober, BR Mullen, MP Slavotinek, AM AF Lin, AE Pober, BR Mullen, MP Slavotinek, AM TI Cardiovascular malformations in Fryns Syndrome: Is there a pathogenic role for neural crest cells? SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital heart defect; conotruncal heart defect; diaphragm defect; diaphragmatic hernia; type B interrupted aortic arch; multiple congenital anomaly/mental retardation syndrome; neural crest ID CONGENITAL DIAPHRAGMATIC-HERNIA; DISTAL DIGITAL HYPOPLASIA; ANOMALY MCA SYNDROME; PRENATAL-DIAGNOSIS; CRANIOFACIAL DYSMORPHISM; HIRSCHSPRUNGS-DISEASE; CARDIAC-MALFORMATIONS; LIMB DEFORMITIES; LETHAL SYNDROME; CYSTIC HYGROMA AB We performed a comprehensive literature and case report review to characterize the cardiovascular malformations (CVMs) associated with Fryns syndrome (OMIM #229850), a multiple congenital anomaly/mental retardation syndrome consisting of diaphragmatic defects, significant pulmonary hypoplasia, distinctive facial appearance, distal digital hypoplasia, and numerous other external and internal anomalies. A total of 112 patients meeting diagnostic guidelines for Fryns syndrome were identified, of whom 82 met narrowly defined criteria (Group 1) and 30 met broader diagnostic criteria (Group 11). Twelve patients reported as having Fryns syndrome with atypical features (Group 111) were also analyzed. A CVM was reported in 51% (42 of 82) of Group I patients, most commonly an atrial or ventricular septal defect (VSD) (23 of 42, 55%). Conotruncal and aortic arch CVMs were common (11 of 42,26%), but not significantly so compared to the general population of infants to age 1 year [Ferencz et al., 1997]. Recognizing that minor septal defects associated with congenital diaphragmatic hernia (CDH) may occur in response to altered hemodynamics (instead of being a bonafide CVM), we excluded four patients reported as having hemo-dynamically insignificant VSDs. Following these exclusions, conotruncal CVMs were found more commonly than in the general population (11 of 38, 29%, P <= 0.025). In Group II, 9 of 30 (30%) had a CVM with no predominant type among the small number of cases reviewed. Among the atypical Fryns syndrome patients in Group 111, half (6 of 12, 50%) had a CVM; most (4 of 6, 67%) were conotruncal, in particular, type B interrupted aortic arch (3 of 4). Patients with Fryns syndrome have a high rate of CVMs, warranting thorough cardiac evaluation including echocardiogram (fetal and/ or postnatal) in all patients, similar to the evaluation for other patients with diaphragmatic hernia. C1 MassGen Hosp Children, Teratol Unit, Serv Pediat, Boston, MA USA. Brigham & Womens Hosp, Teratol Program, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Pediat, Div Genet, San Francisco, CA 94143 USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet & Teratol Unit, 55 Fruit St, Boston, MA 02115 USA. EM lin.angela@mgh.harvard.edu FU NICHD NIH HHS [HD39942-03]; ODCDC CDC HHS [U50/CCU 1132247-03] NR 80 TC 19 Z9 19 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2005 VL 139A IS 3 BP 186 EP 193 DI 10.1002/ajmg.a.31023 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 990PV UT WOS:000233756600002 PM 16283673 ER PT J AU Schwartz, J Park, SK O'Neill, MS Vokonas, PS Sparrow, D Weiss, S Kelsey, K AF Schwartz, J Park, SK O'Neill, MS Vokonas, PS Sparrow, D Weiss, S Kelsey, K TI Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles - Gene-by-drug-by-environment interaction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE genetic polymorphisms; heart rate variability; oxidative stress; particles ID PARTICULATE AIR-POLLUTION; HEART-RATE-VARIABILITY; MYOCARDIAL-INFARCTION; DAILY MORTALITY; CARDIOVASCULAR-DISEASES; HOSPITAL ADMISSIONS; AMBIENT PARTICLES; OXIDATIVE STRESS; EUROPEAN CITIES; NITRIC-OXIDE AB Rationale: Air pollution by particulate matter (PM) has been associated with cardiovascular deaths, although the mechanism of action is unclear. One proposed pathway is through disturbances of the autonomic control of the heart. Objectives: We tested the hypothesis that such disturbances are mediated by PM increasing oxidative stress by examining the association between PM and the high-frequency (HF) component of heart rate variability as modified by the presence or absence of the allele for glutathione-S-transferase M1 (GSTM1) and the use of statins, obesity, high neutrophil counts, higher blood pressure, and older age. Methods: We examined the association between particles less than 2.5 mu M in aerodiameter (PM2.5) and HF in 497 participants in the Normative Aging Study, using linear regression controlling for covariates. Main Results: A 10-mu g/m(3) increase in PM2.5 during the 48 h before HF measurement was associated with a 34% decrease in HF, 95% confidence interval (-9%, -52%), in subjects without the allele, but had no effect in subjects with GSTM1 present. Among GSTM1-null subjects, the use of statins eliminated the effect Of PM2.5. Obesity and high neutrophil counts also worsened the PM effects with or without GSTM1. Conclusion: The effects of PM2.5 on HF appear to be mediated by reactive oxygen species. This may be a key pathway for the adverse effects of combustion particles. C1 Boston Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Schwartz, J (reprint author), Boston Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Landmark Ctr W,Suite 415,401 Pk Dr,POB 15698, Boston, MA 02215 USA. EM jschwrtz@hsph.harvard.edu FU NIEHS NIH HHS [ES00002, 2 T32 ES07069-24, T32 ES07069-22] NR 53 TC 129 Z9 132 U1 1 U2 6 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 DEC 15 PY 2005 VL 172 IS 12 BP 1529 EP 1533 DI 10.1164/rccm.200412-1698OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 994GK UT WOS:000234019000012 PM 16020798 ER PT J AU Jones, A Kwow, CK Kelley, ME Ibrahim, SA AF Jones, A Kwow, CK Kelley, ME Ibrahim, SA TI Racial disparity in knee arthroplasty utilization in the veterans health administration SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; OSTEOARTHRITIS; METAANALYSIS; REPLACEMENT C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15240 USA. Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov NR 13 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2005 VL 53 IS 6 BP 979 EP 981 DI 10.1002/art.21596 PG 3 WC Rheumatology SC Rheumatology GA 995FL UT WOS:000234086100025 PM 16342110 ER PT J AU Attar, EC AF Attar, EC TI Therapeutically targeting leukemia stem cells SO BLOOD LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA AB In the current issue of Blood, Taussig and colleagues demonstrate that cell surface markers previously thought restricted to mature myeloid cells are expressed on both normal hematopoietic stem cells and leukemia stem cells. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2005 VL 106 IS 13 BP 4021 EP 4022 DI 10.1182/blood-2005-09-3853 PG 2 WC Hematology SC Hematology GA 993AU UT WOS:000233925900006 ER PT J AU Richardson, JL Shivdasani, RA Boers, C Hartwig, JH Italiano, JE AF Richardson, JL Shivdasani, RA Boers, C Hartwig, JH Italiano, JE TI Mechanisms of organelle transport and capture along proplatelets during platelet production SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; AXONAL-TRANSPORT; BLOOD-PLATELETS; MOUSE MEGAKARYOCYTES; HIPPOCAMPAL-NEURONS; MICROTUBULES; VESICLES; WHOLE; THROMBOCYTOPOIESIS; ULTRASTRUCTURE AB Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Platelet packaging and release concludes at the tips of each proplatelet. Essential in this process is the distribution of organelles and platelet-specific granules into the nascent platelets. To investigate the mechanism of delivery of organelles into putative platelets, the distribution and dynamics of organelles/granules was monitored. Individual organelles are sent from the cell body to the proplatelets where they move bidirectionally until they are captured at proplatelet ends. Movement occurs at approximately 0.2 mu m/ min, but pauses and changes in direction are frequent. At any given time, approximately 30% of organelles/granules are in motion. Actin poisons do not diminish organelle motion, and vesicular structures are intimately associated with the microltubules. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally on the microtubule arrays of permeabilized proplatelets. Movement of organelles along proplatelets involves 2 mechanisms: organelles travel along microtubules, and the linked microtubules move relative to each other. These studies demonstrate that the components that form platelets are delivered to and assembled de novo along proplatelets. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Italiano, JE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. EM jitaliano@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL 063143, HL68130] NR 55 TC 83 Z9 83 U1 2 U2 10 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 DEC 15 PY 2005 VL 106 IS 13 BP 4066 EP 4075 DI 10.1182/blood-2005-06-2206 PG 10 WC Hematology SC Hematology GA 993AU UT WOS:000233925900018 PM 16118320 ER PT J AU Patel, SR Richardson, JL Schulze, H Kahle, E Galiart, N Drabek, K Shivdasani, RA Hartwig, JH Italiano, JE AF Patel, SR Richardson, JL Schulze, H Kahle, E Galiart, N Drabek, K Shivdasani, RA Hartwig, JH Italiano, JE TI Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes SO BLOOD LA English DT Article ID END-TRACKING PROTEINS; PLATELET FORMATION; CYTOPLASMIC DYNEIN; BLOOD-PLATELETS; TRANSPORT; DYNACTIN; MECHANISMS; INVITRO; SUBUNIT; REVEALS AB Megakaryocytes are terminally differentiated cells that, in their final hours, convert their cytoplasm into long, branched proplatelets, which remodel into blood platelets. Proplatelets elongate at an average rate of 0.85 mu m/min in a microtubule-dependent process. Addition of rhodamine-tubulin to permeabilized proplatelets, immunofluorescence microscopy of the microtubule plus-end marker end-binding protein 3 (EB3), and fluorescence time-lapse microscopy of EB3-green fluorescent protein (GFP)-expressing megakaryocytes reveal that microtubules, organized as bipolar arrays, continuously polymerize throughout the proplatelet. In immature megakaryocytes lacking proplatelets, microtubule plus-ends initiate and grow by centrosomal nucleation at rates of 8.9 to 12.3 mu m/min. In contrast, plus-end growth rates of microtubules within proplatelets are highly variable (1.5-23.5 mu m/ min) and are both slower and faster than those seen in immature cells. Despite the continuous assembly of microtubules, proplatelets continue to elongate when net microtubule assembly is arrested. One alternative mechanism for force generation is microtubule sliding. Triton X-100-permeabilized proplatelets; containing dynein and its regulatory complex, dynactin, but not kinesin, elongate with the addition of adenosine triphosphate (ATP) at a rate of 0.65 mu m/min. Retroviral expression in megakaryocytes of dynamitin (p50), which disrupts dynactin-dynein function, inhibits proplatelet elongation. We conclude that while continuous polymerization of microtubules; is necessary to support the enlarging proplatelet mass, the sliding of overlapping microtubules; is a vital component of proplatelet elongation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Hematol, Boston, MA 02115 USA. Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. RP Italiano, JE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Hematol, Boston, MA 02115 USA. EM jitaliano@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL063143, HL68130, HLO66978-04, HLO7680] NR 32 TC 101 Z9 102 U1 1 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 DEC 15 PY 2005 VL 106 IS 13 BP 4076 EP 4085 DI 10.1182/blood-2005-06-2204 PG 10 WC Hematology SC Hematology GA 993AU UT WOS:000233925900019 PM 16118321 ER PT J AU Gribben, JG Zahrieh, D Stephans, K Bartlett-Pandite, L Alyea, EP Fisher, DC Freedman, AS Mauch, P Schlossman, R Sequist, LV Soiffer, RJ Marshall, B Neuberg, D Ritz, J Nadler, LM AF Gribben, JG Zahrieh, D Stephans, K Bartlett-Pandite, L Alyea, EP Fisher, DC Freedman, AS Mauch, P Schlossman, R Sequist, LV Soiffer, RJ Marshall, B Neuberg, D Ritz, J Nadler, LM TI Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; SPONSORED-WORKING-GROUP; CHAIN GENE STATUS; RESIDUAL DISEASE; MYELODYSPLASTIC SYNDROME; MULTIPLE-MYELOMA; MATCHED ANALYSIS; YOUNGER PATIENTS; DOUBLING TIME; THERAPY AB We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. RP Gribben, JG (reprint author), Barts & London Sch Med, Inst Canc, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA81534]; NIAID NIH HHS [P01AI29530] NR 45 TC 132 Z9 138 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2005 VL 106 IS 13 BP 4389 EP 4396 DI 10.1182/blood-2005-05-1778 PG 8 WC Hematology SC Hematology GA 993AU UT WOS:000233925900060 PM 16131571 ER PT J AU Kadan-Lottick, NS Vanderwerker, LC Block, SD Zhang, BH Prigerson, HG AF Kadan-Lottick, NS Vanderwerker, LC Block, SD Zhang, BH Prigerson, HG TI Psychiatric disorders and mental health service use in patients with advanced cancer - A report from the coping with cancer study SO CANCER LA English DT Article DE cancer; psychiatric morbidity; depression; prevalence; communication; mental health services; palliative care ID BONE-MARROW-TRANSPLANTATION; BREAST-CANCER; TERMINALLY-ILL; COLORECTAL-CANCER; MAJOR DEPRESSION; OF-LIFE; PREVALENCE; MORBIDITY; SURVIVAL; DISTRESS AB BACKGROUND. Psychological morbidity has been proposed as a source of distress in cancer patients. This study aimed to: 1) determine the prevalence of diagnosable psychiatric illnesses, and 2) describe the mental health services received and predictors of service utilization in patients with advanced cancer. METHODS. This was a cross-sectional, multi-institutional study of 251 eligible patients with advanced cancer. Eligibility included: distant metastases, primary therapy failure, nonpaid caregiver, age 20 years, stamina for the interview, English or Spanish-speaking, and adequate cognitive ability. Trained interviewers administered the Structured Clinical Interview for the Diagnostic Statistical Manual IV (DSM-IV) modules for Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder, and a detailed questionnaire regarding mental health service utilization. RESULTS. Overall, 12% met criteria for a major psychiatric condition and 28% had accessed a mental health intervention for a psychiatric illness since the cancer diagnosis. Seventeen percent had discussions with a mental health professional; 90% were willing to receive treatment for emotional problems. Mental health services were not accessed by 55% of patients with major psychiatric disorders. Cancer patients who had discussed psychological concerns with mental health staff (odds ratio [OR] = 19.2; 95% confidence interval [95% CI], 8.90-41.50) and non-Hispanic white patients (OR = 2.7; 95% CI, 1.01-7.43) were more likely to receive mental health services in adjusted analysis. CONCLUSIONS. Advanced cancer patients experience major psychiatric disorders at a prevalence similar to the general population, but affected individuals have a low rate of utilizing mental health services. Oncology providers can enhance utilization of mental health services, and potentially improve clinical outcomes, by discussing mental health concerns with their patients. C1 Yale Univ, Sch Med, Dept Pediat, Sect Pediat Hematol Oncol, New Haven, CT 06520 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. RP Kadan-Lottick, NS (reprint author), Yale Univ, Sch Med, Dept Pediat, Sect Pediat Hematol Oncol, 333 Cedar St,LMP 2073,POB 208064, New Haven, CT 06520 USA. EM nina.kadan-lottick@yale.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NCRR NIH HHS [K12 RR017594, K12RR17594]; NIA NIH HHS [P30 AG021342, P30AG21342]; NIMH NIH HHS [MH56529, MH63892, R01 MH063892] NR 53 TC 107 Z9 112 U1 3 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2005 VL 104 IS 12 BP 2872 EP 2881 DI 10.1002/cncr.21532 PG 10 WC Oncology SC Oncology GA 992JT UT WOS:000233880900028 PM 16284994 ER PT J AU Busuttil, RA Garcia, AM Cabrera, C Rodriguez, A Suh, Y Kim, WH Huang, TT Vijg, J AF Busuttil, RA Garcia, AM Cabrera, C Rodriguez, A Suh, Y Kim, WH Huang, TT Vijg, J TI Organ-specific increase in mutation accumulation and apoptosis rate in CuZn-superoxide dismutase-deficient mice SO CANCER RESEARCH LA English DT Article ID TRANSGENIC MICE; DAMAGE; AGE; BRAIN; LIVER AB Reactive oxygen species have been implicated as a cause of cancer and aging in mammals. Mice deficient for the antioxidant enzyme CuZn-superoxide dismutase (Sod1) have a decreased life span and an elevated incidence of liver cancer. To test the hypothesis that the cancer-prone phenotype in such mice is due to accelerated spontaneous mutation accumulation, we crossed these mutants with mice harboring a neutral lacZ mutation reporter gene. At 2 months of age, the lacZ mutation frequency in the liver of the hybrid animals was already twice as high as in littermate controls of the same age. This difference in mutation frequency increased to > 3-fold at 6 months of age, after which it did not increase any further. Characterization of the mutation spectra in liver of the Sod1-null mice indicated mainly GC-to-TA transversions and GC-to-AT transitions, signature mutations of oxidative stress. The accelerated mutation accumulation in liver was accompanied by an increased frequency of apoptotic cells, as indicated by an increase in both terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling- and caspase 3-stained cells at 6 and 12 months of age. In kidney, an elevated mutation frequency above controls of similar to 2.5-fold was found not earlier than at 6 months. No increased mutation accumulation was observed in brain or spleen. These results support the hypothesis, that oxidative stress is an important causal factor of cancer in mammals. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78240 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78240 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA 94304 USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78240 USA. EM vijg@uthscsa.edu RI Kim, Wooho/G-3703-2011 FU NIA NIH HHS [AG17242, AG20438, AG024400] NR 16 TC 45 Z9 47 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2005 VL 65 IS 24 BP 11271 EP 11275 DI 10.1158/0008-5472.CAN-05-2980 PG 5 WC Oncology SC Oncology GA 996FF UT WOS:000234159100008 PM 16357131 ER PT J AU Krop, I Marz, A Carlsson, H Li, XC Bloushtain-Qimron, N Hu, M Gelman, R Sabel, NS Schnitt, S Ramaswamy, S Kleer, CG Enerback, C Polyak, K AF Krop, I Marz, A Carlsson, H Li, XC Bloushtain-Qimron, N Hu, M Gelman, R Sabel, NS Schnitt, S Ramaswamy, S Kleer, CG Enerback, C Polyak, K TI A putative role for psoriasin in breast tumor progression SO CANCER RESEARCH LA English DT Article ID CARCINOMA IN-SITU; PROTEIN S100A4 P9KA; GENE-EXPRESSION; CANCER PROGRESSION; EPITHELIAL-CELLS; MESSENGER-RNA; METASTASIS; VITRO; INTERACTS; MOTILITY AB Psoriasin (S100A7) was identifi'ed as a gene highly expressed in psoriatic keratinocytes and highly and more frequently expressed in ductal carcinoma in situ (DCIS) than in invasive breast carcinomas (IBC), suggesting a potential role in tumor progression. Psoriasin expression is associated with poor prognostic factors in both DCIS and IBC. Several putative functions have been proposed for psoriasin in various disease types, but none of these can fully explain its involvement in breast tumor progression. Here, we show that down-regulation of endogenous psoriasin expression via stable short hairpin RNAs in a human IBC cell line (MDA-MB-468) increases cell migration and invasion without influencing cell proliferation and survival in vitro but inhibits tumor growth in vivo. These seemingly paradoxical results are potentially explained by the dramatic up-regulation and down-regulation of matrix metalloproteinase-13 and vascular endothelial growth factor (VEGF), respectively, observed in cells with decreased psoriasin levels compared with controls. Correlating with this, high psoriasin expression in human IBC is associated with increased angiogenesis and worse clinical outcome, and psoriasin mRNA levels are coordinately regulated with VEGF and other genes related to hypoxia and mitochondrial reactive oxygen species (ROS). Based on these results, we propose that psoriasin may play a role in breast tumor progression by promoting angiogenesis and enhancing the selection for cells that overcome its anti-invasive function. This hypothesis may explain why psoriasin expression is highest in high-grade and/or estrogen receptor-negative tumors, as these are associated with increased hypoxia and ROS, a setting in which the angiogenic effects of psoriasin are most important. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Canc Res Ctr, Boston, MA 02114 USA. Heinrich Pette Inst, Dept Tumor Virol, Hamburg, Germany. Sahlgrens Univ Hosp, Dept Clin Genet, S-41345 Gothenburg, Sweden. Univ Michigan, Ctr Canc, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Pathol, Ann Arbor, MI 48109 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu FU NCI NIH HHS [CA89393, R01 CA107469] NR 38 TC 63 Z9 69 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 DEC 15 PY 2005 VL 65 IS 24 BP 11326 EP 11334 DI 10.1158/0008-5472.CAN-05-1523 PG 9 WC Oncology SC Oncology GA 996FF UT WOS:000234159100016 PM 16357139 ER PT J AU Woerner, BM Warrington, NM Kung, AL Perry, A Rubin, JB AF Woerner, BM Warrington, NM Kung, AL Perry, A Rubin, JB TI Widespread CXCR4 activation in astrocytomas revealed by phospho-CXCR4-specific antibodies SO CANCER RESEARCH LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; ENDOTHELIAL GROWTH-FACTOR; LOW-GRADE GLIOMAS; MESSENGER-RNA; GRANULE CELLS; BRAIN-TUMORS; CROSS-TALK; EXPRESSION; SURVIVAL; PDGF AB The chemokine receptor CXCR4 is expressed in many cancers,where it may regulate tumor cell growth and migration. The role of CXCR4 in cancer will depend on it being in an activated, signaling state. To better define the significance of CXCR4 expression in cancer, we developed an antibody that can distinguish CXCR4 phosphorylated on serine 339, a residue previously identified as a site for ligand-induced phosphorylation. With this antibody, we investigated the mechanisms of CXCR4 phosphorylation and evaluated the phosphorylation status of CXCR4 in human astrocytomas. In vitro, phosphorylation of serine 339 occurred in response to CXCL12 or epidermal growth factor (EGF) treatment and was increased by protein kinase C activation. In all grades of astrocytomas, CXCR4 was expressed in tumor cells and some endothelial cells, whereas CXCL12 was present in endothelial cells and infiltrating microglia. We found that CXCR4 phosphorylated on serine 339 was present in tumor cells and vascular endothelial cells in all grades of astrocytoma. These data indicate that CXCR4 is expressed and activated in astrocytomas and that phosphorylation of CXCR4 can occur through ligand activation or transactivation via the EGF receptor. These studies extend the potential roles of CXCR4 in cancer to include functions associated with benign (grade 1) tumors. The ability to distinguish phosphorylated CXCR4 will be invaluable for the continued analysis of the role of CXCR4 in cancer and the development of CXCR4 antagonist therapy for patients suffering with primary tumors of the brain and other sites. C1 Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Neuropathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Rubin, JB (reprint author), Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, Campus Box 8208,660 S Euclid, St Louis, MO 63110 USA. EM Rubin_J@kids.wustl.edu OI Perry, Arie/0000-0002-8300-7261; Kung, Andrew/0000-0002-9091-488X FU NICHD NIH HHS [HD01393] NR 56 TC 78 Z9 82 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 DEC 15 PY 2005 VL 65 IS 24 BP 11392 EP 11399 DI 10.1158/0008-5472.CAN-05-0847 PG 8 WC Oncology SC Oncology GA 996FF UT WOS:000234159100024 PM 16357147 ER PT J AU Gunawardane, RN Sgroi, DC Wrobel, CN Koh, E Daley, GQ Brugge, JS AF Gunawardane, RN Sgroi, DC Wrobel, CN Koh, E Daley, GQ Brugge, JS TI Novel role for PDEF in epithelial cell migration and invasion SO CANCER RESEARCH LA English DT Article ID ETS TRANSCRIPTION FACTOR; ANCHORAGE-INDEPENDENT GROWTH; HUMAN BREAST-CANCER; GENE-EXPRESSION; MAMMARY-TUMORS; MESSENGER-RNA; TARGET GENES; C-ETS1; MARKER; TRANSFORMATION AB Cell migration and invasion are two critical cellular processes that are often deregulated during tumorigenesis. To identify factors that contribute to oncogenic progression by stimulating cell migration, we conducted a powerful retroviral based migration screen using an MCF7 cDNA library and the immortalized human breast epithelial cell line MCF-10A. We identified prostate derived Ets factor (PDEF), an Ets transcription factor that is overexpressed in both prostate and breast carcinoma, as a candidate promigratory gene from this screen. Whereas PDEF induced limited motility of MCF-10A cells, coexpression of PDEF with the receptor tyrosine kinases (RTK) ErbR2 and colony-stimulating factor receptor (CSF-IR)/ CSF-1 significantly enhanced MCF-10A motility. Furthermore, cells coexpressing PDEF with either ErbB2 or CSF-IR/CSF-1 induced a dramatic invasive phenotype in three-dimensional cultures. Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway also enhanced PDEF-induced motility and invasion, suggesting that activation of the ERK/ mitogen-activated protein kinase by ErbB2 and CSF-1R/CSF-1 can cooperate with PDEF to promote motility and invasion. Furthermore, PDEF promoted anchorage-independent growth of ErbB2 and CSF-1R/CSF-1-expressing cells. Using laser capture microdissection, we also found that PDEF mRNA is overexpressed in breast tumor epithelia throughout tumor progression. Taken together, these findings suggest that the transcription factor PDEF may play an important role in breast tumorigenesis and that PDEF overexpression may be particularly significant in tumors that exhibit activation of oncogenic RTKs such as ErbB2 and CSF-1R. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Res Unit,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu FU NIGMS NIH HHS [U54 GM064346, U54 GM064346-069036, U54 GM64346-04] NR 37 TC 57 Z9 57 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2005 VL 65 IS 24 BP 11572 EP 11580 DI 10.1158/0008-5472.CAN-05-1196 PG 9 WC Oncology SC Oncology GA 996FF UT WOS:000234159100044 PM 16357167 ER PT J AU Bindra, RS Gibson, SL Meng, A Westermark, U Jasin, M Pierce, AJ Bristow, RG Classon, MK Glazer, PM AF Bindra, RS Gibson, SL Meng, A Westermark, U Jasin, M Pierce, AJ Bristow, RG Classon, MK Glazer, PM TI Hypoxia-induced down-regulation of BRCA1 expression by E2Fs SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; STRAND BREAK REPAIR; DNA-DAMAGE; GENETIC INSTABILITY; TUMOR MICROENVIRONMENT; CANCER-CELLS; CHROMATIN IMMUNOPRECIPITATION; MAMMALIAN-CELLS; CARCINOMAS; ATM AB Decreased BRCA1 expression in the absence of genetic mutation is observed frequently in sporadic cancers of the breast and other sites, although little is known regarding the mechanisms by which the expression of this gene can be repressed. Here, we show that activating and repressive E2Fs simultaneously bind the BRCA1 promoter at two adjacent E2F sites in vivo, and that bypoxia induces a dynamic redistribution of promoter occupancy by these factors resulting in the transcriptional repression of BRCA1 expression. Functionally, we show that hypoxia is associated with impaired homologous recombination, whereas the nonhomologous end-joining (NHEJ) repair pathway is unaffected tinder these conditions. Repression of BRCA1 expression by hypoxia represents an intriguing mechanism of functional BRCA1 inactivation in the absence of genetic mutation. We propose that hypoxia-induced decreases in BRCA1 expression and consequent suppression of homologous recombination may lead to genetic instability by shifting the balance between the high-fidelity homologous recombination pathway and the error-prone NHEJ pathway of DNA repair. Furthermore, these findings provide a novel link between E2Fs and the transcriptional response to hypoxia and provide insight into the mechanisms by which the tumor microenvironment can contribute to genetic instability in cancer. C1 Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Univ Hlth Network, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40506 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Glazer, PM (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, POB 208040, New Haven, CT 06520 USA. EM peter.glazer@yale.edu FU NIEHS NIH HHS [ES05775]; NIGMS NIH HHS [GM07205] NR 50 TC 142 Z9 144 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 DEC 15 PY 2005 VL 65 IS 24 BP 11597 EP 11604 DI 10.1158/0008-5472.CAN-05-2119 PG 8 WC Oncology SC Oncology GA 996FF UT WOS:000234159100047 PM 16357170 ER PT J AU Tai, YT Li, XF Catley, L Coffey, R Breitkreutz, I Bae, J Song, WH Podar, K Hideshima, T Chauhan, D Schlossman, R Richardson, P Treon, SP Grewal, IS Munshi, NC Anderson, KC AF Tai, YT Li, XF Catley, L Coffey, R Breitkreutz, I Bae, J Song, WH Podar, K Hideshima, T Chauhan, D Schlossman, R Richardson, P Treon, SP Grewal, IS Munshi, NC Anderson, KC TI Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: Clinical implications SO CANCER RESEARCH LA English DT Article ID NATURAL-KILLER-CELLS; GROWTH-FACTOR SECRETION; NON-HODGKINS-LYMPHOMA; IN-VIVO; THERAPEUTIC APPLICATIONS; MONOCLONAL-ANTIBODY; THALIDOMIDE ANALOGS; INTERLEUKIN-2; APOPTOSIS; CANCER AB SGN-40, a humanized immoglobulin G1 (IgG1) anti-CD40 monoclonal antibody, mediates cytotoxicity against human multiple myeloma (MM) cells via suppression of interleukin (IL)-6-induced proliferative and antiapoptotic effects as well as antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we studied the clinical significance of an immunomodulatory drug lenalidomide on SGN-40-induced cytotoxicity against CD138(+)CD40(+) MM lines and patient MM cells. Pretreatment with lenalidomide sensitized MM cells to SGN-40-induced cell death. Combined lenalidomide and SGN-40 significantly induced MM apoptosis, evidenced by enhanced cleavage of caspase-3/8/poly(ADP-ribose)polymerase and increased sub-G(0) cells, compared with either single agent at the same doses. Pretreatment of effector cells with lenalidomide augmented SGN-40-induced MM cell lysis, associated with an increased number of CD56(+)CD3(+) natural killer (NK) cells expressing CD16 and LFA-1. Importantly, pretreatment with lenalidomide or lenalidomide and SGN-40 markedly enhanced NK-cell-mediated lysis of autologous patient MM cells triggered by SGN-40. Lenalidomide also up-regulated CD40L on CD56(+)CD3(-) NK cells, facilitating IL-2-mediated activation of NK cells. In addition, lenalidomide induced the CD56(dim) NK subset, which are more potent mediators of ADCC against target MM cells than the CD56(bright) INK subset. Finally, pretreatment of both effector and target MM cells with lenalidomide markedly enhanced SGN-40-mediated ADCC against CD40-expressing MM cells. These studies, therefore, show that the addition of lenalidomide to SGN-40 enhances cytotoxicity against MM cells, providing the framework for combined lenalidomide and SGN-40 in a new treatment paradigm to both target MM cells directly and induce immune effectors against MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Seattle Genet Inc, Bothell, WA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, M557,44 Biney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [R0-1 50947, P01-78378] NR 31 TC 117 Z9 122 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 DEC 15 PY 2005 VL 65 IS 24 BP 11712 EP 11720 DI 10.1158/0008-5472.CAN-05-1657 PG 9 WC Oncology SC Oncology GA 996FF UT WOS:000234159100060 PM 16357183 ER PT J AU Hideshima, T Bradner, JE Chauhan, D Anderson, KC AF Hideshima, T Bradner, JE Chauhan, D Anderson, KC TI Intracellular protein degradation and its therapeutic implications SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; PROTEASOME INHIBITOR PS-341; AGGRESOME FORMATION; DRUG-RESISTANCE; THALIDOMIDE; CYTOTOXICITY; ACCUMULATION; AGGREGATION; BORTEZOMIB; ANALOGS C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 30 TC 34 Z9 34 U1 2 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 DEC 15 PY 2005 VL 11 IS 24 BP 8530 EP 8533 DI 10.1158/1078-0432.CCR-05-2305 PN 1 PG 4 WC Oncology SC Oncology GA 998YR UT WOS:000234356300002 PM 16361533 ER PT J AU Aghi, M Gaviani, P Henson, JW Batchelor, TT Louis, DN Barker, FG AF Aghi, M Gaviani, P Henson, JW Batchelor, TT Louis, DN Barker, FG TI Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; FACTOR EXPRESSION; MULTIFORME; MRI; SURVIVAL; GLIOMAS; CELLS; OVEREXPRESSION; INHIBITORS; GRADE AB Purpose: Two clinical-molecular glioblastoma subtypes have been described: "primary" glioblastomas arise de novo in older patients and often overexpress epidermal growth factor receptor (EGFR); "secondary" glioblastomas progress from lower-grade tumors in younger patients and commonly have TP53 mutations. EGFR overexpression correlates in experimental gliomas with increased angiogenesis, edema, and invasion. No radiographic predictors of molecular glioblastoma subtype are known. Experimental Design: We retrospectively reviewed 75 glioblastomas, classified as TP53 mutated (n = 11), EGFR-amplified (n = 31), or neither (non-TP53/non-EGFR; n = 33). Four variables were derived from preoperative magnetic resonance imaging: (a) T2/T1, the ratio of T2-bright volume to enclosed T1 -enhancing volume; (b) percentage of tumor volume that was necrosis; and (c and d) T1 and T2 border sharpness coefficients (BSC), the rates of change in grayscale intensity of adjacent 0.02- cm(2) voxels traversing the anterior, posterior, and lateral borders on T1 -enhanced and T2 images. Results and Conclusions: MeanT2/T1 was 4.7 for EGFR-amplified glioblastomas, greater than that of TP53-mutated glioblastomas (2,3) or non-TP53/non-EGFR glioblastomas (2.6; P < 0.00005). All four tumors with T2/T1 > 7.2 were EGFR-amplified; 0 of 15 with T2/T1 < 4.7 underwent gross total resection. The mean T2 BSC of EGFR-amplified glioblastomas was 33.7, less sharp (P < 0.0000005) than TP53-mutated (72.2) and non-TP53/non-EGFR glioblastomas (81.2). All 15 glioblastomas with T2 BSC < 30.8 were EGFR-amplified. Percentage necrosis and T1 BSC did not differ between glioblastoma subtypes. The increased T2/T1 ratio and decreased T2 BSC in EGFR-overexpressing tumors are the first radiographic distinctions described between glioblastoma molecular subtypes.These findings may reflect increased angiogenesis, edema, and/or invasion in EGFR-overexpressing tumors. C1 Massachusetts Gen Hosp, Dept Neurosurg, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stephen e & Catherine Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neuro Oncol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Aghi, M (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Neurosurg Serv, Room 502,White Bldg,55 Fruit St, Boston, MA 02114 USA. EM maghi@partners.org FU NCI NIH HHS [CA57683] NR 28 TC 47 Z9 50 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 DEC 15 PY 2005 VL 11 IS 24 BP 8600 EP 8605 DI 10.1158/1078-0432.CCR-05-0713 PN 1 PG 6 WC Oncology SC Oncology GA 998YR UT WOS:000234356300012 PM 16361543 ER PT J AU Schittenhelm, MM Oechsle, K Kollmannsberger, C Honecker, F Weber, DA Tillner, J Corless, C Heinrich, MC Bokemeyer, C AF Schittenhelm, MM Oechsle, K Kollmannsberger, C Honecker, F Weber, DA Tillner, J Corless, C Heinrich, MC Bokemeyer, C TI Association of EGFR and KRAS mutation status and clinical response to the anti-epidermal growth factor receptor (EGFR) monoclonal antibody matuzumab (M, EMD-72000) and paclitaxel (P) in a phase I study of patients (pts) with advanced non-small cell lung C. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Tubingen Hosp, Dept Hematol Oncol, Tubingen, Germany. OHSU, Canc Inst Portland, Portland, OR USA. Univ Hamburg, Hosp Eppendorf, Dept Hematol Oncol, D-20246 Hamburg, Germany. Merck KGaA, Darmstadt, Germany. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8992S EP 8993S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700118 ER PT J AU Reardon, DA Wen, PY Lyons, P Rich, JN Berk, L Knowles, HL Rivera, VM Bedrosian, CL Friedman, HS AF Reardon, DA Wen, PY Lyons, P Rich, JN Berk, L Knowles, HL Rivera, VM Bedrosian, CL Friedman, HS TI A phase I trial of AP23573, a novel mTOR inhibitor, in patients (Pts) with recurrent malignant glioma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9012S EP 9012S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700197 ER PT J AU Lewis, N Eder, JP Connolly, MM Guo, F Pierce, KJ Olszanski, AJ AF Lewis, N Eder, JP Connolly, MM Guo, F Pierce, KJ Olszanski, AJ TI Phase 1 study of the safety, tolerability and pharmacolkinetics of oral CP-868,596, a highly specific PDGFR inhibitor in patients with advanced cancers. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Ctr, Boston, MA USA. Pfizer Oncol, New London, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9021S EP 9021S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700230 ER PT J AU LoRusso, P Appleman, L Heath, E Malburg, L Zhu, AX Carey, M Shapiro, GI Eder, JP AF LoRusso, P Appleman, L Heath, E Malburg, L Zhu, AX Carey, M Shapiro, GI Eder, JP TI A phase 1 study of a novel spectrum selective inhibitor (SSKI), XL880, administered orally in patients with advanced solid malignancies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Karmanos Canc Ctr, Detroit, MI USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9025S EP 9025S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700247 ER PT J AU Davis, D Heymach, J McConkey, D Desai, J George, S Jackson, J Bello, C Baum, C Shalinsky, D Demetri, G AF Davis, D Heymach, J McConkey, D Desai, J George, S Jackson, J Bello, C Baum, C Shalinsky, D Demetri, G TI Receptor tyrosine kinase activity and apoptosis in gastrointestinal stromal tumours: A pharmacodynamic analysis of response to sunitinib malate (SU11248) therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Global R&D, La Jolla, CA USA. NR 0 TC 0 Z9 0 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9027S EP 9027S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700255 ER PT J AU Demetri, GD Bauer, S Dileo, P van den Abbeele, A George, S Morgan, J Veronese, L Alland, L Massimini, G Salesi, J Quigley, MT Pokela, J Denise, C Manley, P Fletcher, JA AF Demetri, GD Bauer, S Dileo, P van den Abbeele, A George, S Morgan, J Veronese, L Alland, L Massimini, G Salesi, J Quigley, MT Pokela, J Denise, C Manley, P Fletcher, JA TI Activity of AMN107, a novel kinase inhibitor, in gastrointestinal stromal tumor (GIST): Preclinical rationale and early clinical results with imatinib-resistant GIST. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ludwig Ctr Canc Res, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Novartis Oncol, Basel, Switzerland. RI Bauer, Sebastian/D-8120-2012 OI Bauer, Sebastian/0000-0001-5949-8120 NR 0 TC 0 Z9 0 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9030S EP 9030S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700267 ER PT J AU Baker, LH Ryan, C Agarwala, S Cranmer, L Blackstein, M D'Amato, G Mendelson, D Hurwitz, C McLeod, M Dahl, T Sherman, MS AF Baker, LH Ryan, C Agarwala, S Cranmer, L Blackstein, M D'Amato, G Mendelson, D Hurwitz, C McLeod, M Dahl, T Sherman, MS TI Preliminary results of a phase 2 study of the novel heat shock protein 70 (hsp70) inducer, STA-4783, in combination with paclitaxel in patients with soft tissue sarcomas. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Michigan, Ann Arbor, MI 48109 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA 15260 USA. Arizona Canc Ctr, Tucson, AZ USA. Univ Toronto, Toronto, ON, Canada. H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Arizona Canc Ctr, Scottsdale, AZ USA. Synta Pharmaceut, Lexington, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9058S EP 9058S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700381 ER PT J AU Houk, BE Bello, C Garrett, M Poland, B Wagg, J Wada, R Motzer, R Rosen, L Demetri, G AF Houk, BE Bello, C Garrett, M Poland, B Wagg, J Wada, R Motzer, R Rosen, L Demetri, G TI Population pharmacokinetic (PK)-pharmacodynamic (PD) meta-analysis of sunitinib malate (SU11248) efficacy and tolerability endpoints in gastrointestinal stromal tumor (GIST), metastatic renal cell carcinoma (MRCC) and solid tumor patients. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Pfizer Global R&D, La Jolla, CA USA. Pharsight Corp, Mountain View, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9075S EP 9076S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701027 ER PT J AU Rivera, VM Berk, L Chawla, SP Daly, ST Sankhala, KK Clackson, T Bedrosian, CL Demetri, GD AF Rivera, VM Berk, L Chawla, SP Daly, ST Sankhala, KK Clackson, T Bedrosian, CL Demetri, GD CA AP23573 Sarcoma Study Grp TI Analysis of potential biomarkers of AP23573 activity in a phase II trial in sarcoma patients. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 AP23573 Sarcoma Study Grp, Cambridge, MA USA. ARIAD Pharmaceut Inc, Cambridge, MA USA. Cent City Doctors Hosp, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9077S EP 9078S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701034 ER PT J AU Nicholson, B Chao, TH Deyanat-Yazdi, G Claassen, G Chauhan, D Anderson, KC Lloyd, GK Palladino, MA Neuteboom, STC AF Nicholson, B Chao, TH Deyanat-Yazdi, G Claassen, G Chauhan, D Anderson, KC Lloyd, GK Palladino, MA Neuteboom, STC TI The novel proteasome inhibitor NPI-0052 inhibits NF-KB DNA binding activity more potently and rapidly than bortezomib (Velcade (TM)) in human multiple myeloma and prostate cancer cell lines. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Nereus Pharmaceut Inc, San Diego, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9081S EP 9081S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701050 ER PT J AU Rattan, R Giri, S Singh, AK Singh, I AF Rattan, R Giri, S Singh, AK Singh, I TI AICAR (5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside) inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase (AMPIK). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9110S EP 9110S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701165 ER PT J AU Bauer, S Yu, L Read, M Normant, E Demetri, GD Fletcher, JA AF Bauer, S Yu, L Read, M Normant, E Demetri, GD Fletcher, JA TI IPI504, a novel HSP90 inhibitor, causes inhibition and degradation of KIT in imatinib-resistant GIST: Rationale for therapeutic targeting in GIST. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Harvard Univ, Dept Pathol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Infin Pharmaceut, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Bauer, Sebastian/D-8120-2012 OI Bauer, Sebastian/0000-0001-5949-8120 NR 0 TC 2 Z9 2 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9111S EP 9111S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701170 ER PT J AU Cho, DC Signoretti, S Regan, M McDermott, D Polivy, A Youmans, A Stanbridge, E Atkins, M AF Cho, DC Signoretti, S Regan, M McDermott, D Polivy, A Youmans, A Stanbridge, E Atkins, M TI Low expression of surrogates for mTOR pathway activation predicts resistance to CCI-779 in patients with advanced renal cell carcinoma (RCC). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Dana Farber Canc Ctr, Renal Canc Program, Boston, MA USA. Univ Calif Irvine, Coll Med, Irvine, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9133S EP 9134S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701257 ER PT J AU Yan, X Shen, H Jiang, HJ Hu, D Zhang, CS Wang, J Wu, XQ AF Yan, X Shen, H Jiang, HJ Hu, D Zhang, CS Wang, J Wu, XQ TI Targeting Akt, ERK and NF-kappa B pathways by external Qi of Yan Xin Qigong: Differential cytotoxic effect on cancer and normal cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Inst Chongqing Tradit Chinese Med, Chongqing, Peoples R China. New Med Sci Res Inst, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RI Hu, Dan/D-9642-2015 NR 0 TC 0 Z9 0 U1 0 U2 10 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 DEC 15 PY 2005 VL 11 IS 24 SU S BP 9134S EP 9134S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701259 ER PT J AU Chawla, SP Blay, JY Staddon, AP D'Amato, GZ Tolcher, AW Sankhala, KK Daly, ST Bedrosian, CL Demetri, GD AF Chawla, SP Blay, JY Staddon, AP D'Amato, GZ Tolcher, AW Sankhala, KK Daly, ST Bedrosian, CL Demetri, GD CA AP23573 Sacoma Study Grp TI A phase II trial of AP23573, a novel mTOR inhibitor, in patients (Pts) with advanced soft tissue or bone sarcoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Century City Doctors Hosp, Los Angeles, CA USA. John Wayne Canc Inst, Los Angeles, CA USA. Ctr Leon Berard, F-69373 Lyon, France. Penn Oncol Hematol Associates, Philadelphia, PA USA. Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9166S EP 9166S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701392 ER PT J AU Grinspoon, S AF Grinspoon, S TI Androgen deficiency and HIV infection SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; WASTING SYNDROME; MEN; TESTOSTERONE; WOMEN; HYPOGONADISM; WEIGHT; BODY C1 Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutrit Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 12 TC 19 Z9 19 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2005 VL 41 IS 12 BP 1804 EP 1805 DI 10.1086/498320 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UB UT WOS:000233698300019 PM 16288407 ER PT J AU Rodriguez, M Chou, S Fisher, DC De Girolami, U Amato, AA Marty, FM AF Rodriguez, M Chou, S Fisher, DC De Girolami, U Amato, AA Marty, FM TI Lyme meningoradiculitis and myositis after allogeneic hematopoietic stem cell transplantation SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BORRELIA-BURGDORFERI; NEUROLOGIC MANIFESTATIONS; DISEASE; NEUROBORRELIOSIS; DIAGNOSIS; MUSCLE AB We describe a patient with a history of allogeneic hematopoietic stem cell transplantation complicated by chronic graft-versus-host disease who developed painful meningo-radiculitis and myositis due to Lyme borreliosis. To our knowledge, this is the first report of such an infection occurring after allogeneic hematopoietic stem cell transplantation in the United States. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org RI Chou, Sherry/G-5779-2015 NR 18 TC 6 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2005 VL 41 IS 12 BP E112 EP E114 DI 10.1086/498154 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UB UT WOS:000233698300033 PM 16288389 ER PT J AU Babu, K Bahri, S Alphey, L Chia, W AF Babu, K Bahri, S Alphey, L Chia, W TI Bifocal and PP1 interaction regulates targeting of the R-cell growth cone in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Article DE bifocal; protein phosphatase-1 (PP1); axon guidance; photoreceptors; optic lobe; cytoskeleton; F-actin ID PHOTORECEPTOR AXON GUIDANCE; RECEPTOR TYROSINE PHOSPHATASES; 1ST OPTIC GANGLION; PROTEIN PHOSPHATASE-1; VISUAL-SYSTEM; ADAPTER PROTEIN; MAMMALIAN INHIBITOR-2; NUCLEAR INHIBITOR; RETINAL AXONS; EMBRYONIC CNS AB Bifocal is a putative cytoskeletal regulator and a Protein phosphatase-1 (PP1) interacting protein that mediates normal photoreceptor morphology in Drosophilia. We show here that Bif and PP1-97B as well as their ability to interact with each other are required for photoreceptor growth cone targeting in the larval visual system. Single mutants for bif or PP1-878 show defects in axonal projections in which the axons of the outer photoreceptors bypass the lamina, where they normally terminate. The data show that the functions of bif and PP1-87B in either stabilizing R-cell morphology (for Bif) or regulating the cell cycle (for PP1-87B) can be uncoupled from their function in visual axon targeting. Interestingly, the axon targeting phenotypes are observed in both PPI-87B mutants and PP1-87B overexpression studies, suggesting that all optimal PP1 activity may be required for normal axon targeting. bif mutants also display strong genetic interactions with receptor tyrosine phosphatases, dptp10d and dptp69d, and biochemical studies demonstrate that Bif interacts directly with F-actin in vitro. We propose that. as a downstream component of axon signaling pathways, Bif regulates PP1 activity, and both proteins influence cytoskeleton dynamics in the growth cone of R cells to allow proper axon targeting. (c) 2005 Elsevier Inc. All rights reserved . C1 Natl Univ Singapore, Temasek Life Sci Lab, Singapore 117604, Singapore. Natl Univ Singapore, Dept Biol Sci, Singapore 117604, Singapore. Inst Mol & Cell Biol, Proteos 138673, Singapore. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. RP Babu, K (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Richard B Simches Res Bldg,185 Cambridge St,CPZN, Boston, MA 02114 USA. EM kavita@molbio.mgh.harvard.edu RI ASTAR, IMCB/E-2320-2012 FU Wellcome Trust NR 70 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2005 VL 288 IS 2 BP 372 EP 386 DI 10.1016/j.ydbio.2005.09.017 PG 15 WC Developmental Biology SC Developmental Biology GA 000IW UT WOS:000234455900006 PM 16280124 ER PT J AU Kennedy, RD D'Andrea, AD AF Kennedy, RD D'Andrea, AD TI The Fanconi Anemia/BRCA pathway: new faces in the crowd SO GENES & DEVELOPMENT LA English DT Review DE BRCA; cancer; chemotherapy; DNA cross-links; DNA helicase; Fanconi Anemia ID DNA-DAMAGE RESPONSE; ACUTE MYELOID-LEUKEMIA; DOUBLE-STRAND BREAKS; HOMOLOGY-DIRECTED REPAIR; BLOOMS-SYNDROME HELICASE; S-PHASE; NUCLEAR ACCUMULATION; BRCA PATHWAY; CROSS-LINKS; DEUBIQUITINATING ENZYMES AB Over the past few years, study of the rare inherited chromosome instability disorder, Fanconi Anemia (FA), has uncovered a novel DNA damage response pathway. Through the cooperation of multiple proteins, this pathway regulates a complicated cellular response to DNA cross-linking agents and other genotoxic stresses. In this article we review recent data identifying new components of the FA pathway that implicate it in several aspects of the DNA damage response, including the direct processing of DNA, translesion synthesis, homologous recombination, and cell cycle regulation. We also discuss new findings that explain how the FA pathway is regulated through the processes of ubiquitination and deubiquitination. We then consider the clinical implications of our current understanding of the FA pathway, particularly in the development and treatment of malignancy in heterozygous carriers of FA mutations or in patients with sporadic cancers. We consider how recent studies of p53-mediated apoptosis and loss of p53 function in models of FA may help explain the clinical features of the disease and finally present a hypothesis to account for the specificity of the FA pathway in the response to DNA cross-links. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 NR 135 TC 264 Z9 268 U1 2 U2 20 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2005 VL 19 IS 24 BP 2925 EP 2940 DI 10.1101/gad.1370505 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 995JB UT WOS:000234095500001 PM 16357213 ER PT J AU Terada, S Yoshimoto, H Fuchs, JR Sato, M Pomerantseva, I Selig, MK Hannouche, D Vacanti, JP AF Terada, S Yoshimoto, H Fuchs, JR Sato, M Pomerantseva, I Selig, MK Hannouche, D Vacanti, JP TI Hydrogel optimization for cultured elastic chondrocytes seeded onto a polyglycolic acid scaffold SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Plastic-Surgery-Research-Council CY APR 17-20, 2002 CL BOSTON, MA SP Plast Surg Res Council ID PLURONIC F-127 GELS; UNSATURATED FATTY-ACIDS; PHARMACEUTICAL APPLICATION; BIOMEDICAL POLYMERS; METHYLCELLULOSE; CELLS; ABSORPTION; ALGINATE; DELIVERY; INSULIN AB purpose of this study was to compare the effect of different hydrogels on the production of tissue-engineered cartilage based on polyglycolic acid (PGA). Chondrocytes were isolated from adult sheep auricles. Alginate, Type I collagen, methylcellulose, and pluronic F127 hydrogels were evaluated, as were controls prepared without hydrogels. Proliferated chondrocytes were mixed with each hydrogel at 20 X 10(6) cells/mL and seeded onto PGA (1. X 1 X 0.2 cm, n = 60). The constructs were cultured with serum-free medium containing 5 ng/mL TGF-beta(2), and 5 ng/mL des(1-3)IGF-I in rotational bioreactors for up to 6 weeks. The cellular morphology, histology, and biochemistry were analyzed. Type I collagen, methylcellulose, and pluronic F127 displayed improved cartilage matrix deposition in terms of histology and biochemistry compared to alginate. It was not concluded that the combined seeding of chondrocytes and hydrogels on a PGA scaffold had significantly better effects than cell seeding without hydrogels. However, the histology and Other useful findings in this ECM analyses suggested that Type I collagen and MC hydrogels were the best candidates for cartilage regeneration, because of their Stimulation for chondrocyte proliferation in a three-dimensional culture as well as cartilage regeneration. (c) 2005 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Electron Microscopy Unit, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Lab Tissue Engn & Organ Fabricat, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org NR 46 TC 33 Z9 34 U1 2 U2 6 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 DEC 15 PY 2005 VL 75A IS 4 BP 907 EP 916 DI 10.1002/jbm.a.30505 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 989RD UT WOS:000233690500016 PM 16138328 ER PT J AU Dong, CZ Kumar, S Choi, WT Madani, N Tian, SM An, J Sodroski, JG Huang, ZW AF Dong, CZ Kumar, S Choi, WT Madani, N Tian, SM An, J Sodroski, JG Huang, ZW TI Different stereochemical requirements for CXCR4 binding and signaling functions as revealed by an anti-HIV, D-amino acid-containing SMM-chemokine ligand SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR CXCR4; ENTRY; LESTR/FUSIN; SDF-1; CCR-5 AB Human immunodeficiency virus type 1 (HIV-1) uses a chemokine receptor, usually CXCR4 or CCR5, for entry into the target cells. Here, we used a chemical biology approach to demonstrate that binding and signaling domains in CXCR4 are possibly distinct and separate, as the new analogue, D(1-10)-vMIP-II-(9-68)-SDF-1 alpha (RCP222), could not activate CXCR4 despite the fact that its binding activity was comparable to that of stromal cell-derived factor (SDF)-1 alpha, the only natural ligand of CXCR4. C1 Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Raylight Corp, Chemokine Pharmaceut Inc, La Jolla, CA 92037 USA. RP Huang, ZW (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ziweihuang@burnham.org NR 15 TC 16 Z9 16 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 15 PY 2005 VL 48 IS 25 BP 7923 EP 7924 DI 10.1021/jm050829u PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 992ZR UT WOS:000233923000002 PM 16335916 ER PT J AU Brown, DA Chicco, AJ Jew, KN Johnson, MS Lynch, JM Watson, PA Moore, RL AF Brown, DA Chicco, AJ Jew, KN Johnson, MS Lynch, JM Watson, PA Moore, RL TI Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the K(ATP) channel in the rat SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; SENSITIVE POTASSIUM CHANNELS; INFARCT SIZE; IN-VIVO; PRECONDITIONING PROTECTS; MYOCARDIAL-INFARCTION; CONSCIOUS RABBITS; BETA-OXIDATION; CORONARY FLOW; H9C2 CELLS AB This study was conducted to examine the role of myocardial ATP-sensitive potassium (K(ATP)) channels in exercise-induced protection from ischaemia-reperfusion (I-R) injury. Female rats were either sedentary (Sed) or exercised for 12 weeks (Tr). Hearts were excised and underwent a 1-2 h regional I-R protocol. Prior to ischaemia, hearts were subjected to pharmacological blockade of the sarcolemmal K(ATP) channel with HMR 1098 (SedHMR and TrHMR), mitochondrial blockade with 5-hydroxydecanoic acid (5HD; Sed5HD and Tr5HD), or perfused with buffer containing no drug (Sed and Tr). Infarct size was significantly smaller in hearts from Tr animals (35.4 +/- 2.3 versus 44.7 +/- 3.0% of the zone at risk for Tr and Sed, respectively). Mitochondrial K(ATP) blockade did not abolish the training-induced infarct size reduction (30.0 +/- 3.4 versus 38.0 +/- 2.6 in Tr5HD and Sed5HD, respectively); however, sarcolemmal K(ATP) blockade completely eradicated the training-induced cardioprotection. Infarct size was 71.2 +/- 3.3 and 64.0 +/- 2.4% of the zone at risk for TrHMR and Sed HMR. The role of sarcolemmal K(ATP) channels in Tr-induced protection was also supported by significant increases in both subunits of the sarcolemmal K(ATP) channel following training. LV developed pressure was better preserved in hearts from Tr animals, and was not influenced by addition of HMR 1098. 5HD decreased pressure development regardless of training status, from 15 min of ischaemia through the duration of the protocol. This mechanical dysfunction was likely to be due to a 5HD-induced increase in myocardial Ca(2+) content following I-R. The major findings of the present study are: (1) unlike all other known forms of delayed cardioprotection, infarct sparing following chronic exercise was not abolished by 5HD; (2) pharmacological blockade of the sarcolemmal K(ATP) channel nullified the cardioprotective benefits of exercise training; and (3) increased expression of sarcolemmal K(ATP) channels was observed following chronic training. C1 Univ Colorado, Cardiovasc Inst, Dept Integrat Physiol, Boulder, CO 80309 USA. Univ Colorado, Dept Med, Div Endocrinol, Denver, CO 80112 USA. Denver Hlth Sci Ctr, Denver, CO 80112 USA. Denver VA Med Ctr, Denver, CO 80112 USA. RP Moore, RL (reprint author), Univ Colorado, Cardiovasc Inst, Dept Integrat Physiol, Boulder, CO 80309 USA. EM russell.moore@colorado.edu RI Moore, Russell/D-1040-2013 OI Moore, Russell/0000-0002-6727-8985 FU NHLBI NIH HHS [HL40306, HL72790, R01 HL040306, R01 HL072790]; NIGMS NIH HHS [R25 GM066728, GM066728-01] NR 71 TC 68 Z9 70 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2005 VL 569 IS 3 BP 913 EP 924 DI 10.1113/jphysiol.2005.095729 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 991JC UT WOS:000233808300018 PM 16223762 ER PT J AU Ecker, JL Harris, NL Williams, WW Steele, DJR Rahemtullah, A Thadhani, R Colvin, RB AF Ecker, JL Harris, NL Williams, WW Steele, DJR Rahemtullah, A Thadhani, R Colvin, RB TI Case 38-2005: A 29-year-old pregnant woman with the nephrotic syndrome and hypertension - Combined membranous (class V) and diffuse segmental proliferative and sclerosing (class IV-S [A/C]) lupus nephritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PLACENTAL PATHOLOGY; TYROSINE KINASE-1; RENAL BIOPSY; ERYTHEMATOSUS; PREECLAMPSIA; RISK; GLOMERULONEPHRITIS; CLASSIFICATION; NEPHROPATHY; ANTIBODIES C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Transplant Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Div Nephrol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. NR 23 TC 17 Z9 17 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 DEC 15 PY 2005 VL 353 IS 24 BP 2590 EP 2600 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 993BA UT WOS:000233926500010 ER PT J AU Chen, J Lee, BH Williams, IR Kutok, JL Mitsiades, CS Duclos, N Cohen, S Adelsperger, J Okabe, R Coburn, A Moore, S Huntly, BJP Fabbro, D Anderson, KC Griffin, JD Gilliland, DG AF Chen, J Lee, BH Williams, IR Kutok, JL Mitsiades, CS Duclos, N Cohen, S Adelsperger, J Okabe, R Coburn, A Moore, S Huntly, BJP Fabbro, D Anderson, KC Griffin, JD Gilliland, DG TI FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies SO ONCOGENE LA English DT Article DE fibroblast growth factor receptor 3 (FGFR3); multiple myeloma; small molecule tyrosine inhibitor; murine bone marrow transplant (BMT) assay ID GROWTH-FACTOR RECEPTOR-3; ACUTE MYELOGENOUS LEUKEMIA; MYELOMA CELL-LINES; MULTIPLE-MYELOMA; KINASE INHIBITOR; TYROSINE KINASE; THANATOPHORIC DYSPLASIA; ACTIVATING MUTATIONS; SIGNAL-TRANSDUCTION; IMATINIB MESYLATE AB Reccurent chromosomal translocation t(4;14) (p16.3;q32.3) occurs in patients with multiple myeloma (MM) and is associated with ectopic overexpression of fibroblast growth factor receptor 3 (FGFR3) that sometimes may contain the activation mutations such as K650E thanatophoric dysplasia type II (TDII). Although there have been significant advances in therapy for MM including the use of proteasome inhibitors, t(4;14) MM has a particularly poor prognosis and most patients still die from complications related to their disease or therapy. One potential therapeutic strategy is to inhibit FGFR3 in those myeloma patients that overexpress the receptor tyrosine kinase due to chromosomal translocation. Here we evaluated PKC412, a small molecule tyrosine kinase inhibitor, for treatment of FGFR3-induced hematopoietic malignancies. PKC412 inhibited kinase activation and proliferation of hematopoietic Ba/F3 cells transformed by FGFR3 TDII or a TEL-FGFR3 fusion. Similar results were obtained in PKC412 inhibition of several different t(4;14)-positive human MM cell lines. Further more, treatment with PKC412 resulted in a statistically significant prolongation of survival in murine bone marrow transplant models of FGFR3 TDII-induced pre-B cell lymphoma, or a peripheral T-cell lymphoma associated TEL-FGFR3 fusion-induced myeloproliferative disease. These data indicate that PKC412 may be a useful molecularly targeted therapy for MM associated with overexpression of FGFR3, and perhaps other diseases associated with dysregulation of FGFR3 or related mutants. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol, Childrens Hosp Res Bldg,1 Blackfan Circle,5th Flo, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011; huntly, brian/E-6725-2014 OI Williams, Ifor/0000-0002-8810-2911; huntly, brian/0000-0003-0312-161X FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654]; PHS HHS [P0-1 78378, R01 50947] NR 47 TC 66 Z9 69 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 15 PY 2005 VL 24 IS 56 BP 8259 EP 8267 DI 10.1038/sj.onc.1208989 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 993LV UT WOS:000233956500005 PM 16091734 ER PT J AU Kumar, ATN Skoch, J Bacskai, BJ Boas, DA Dunn, AK AF Kumar, ATN Skoch, J Bacskai, BJ Boas, DA Dunn, AK TI Fluorescence-lifetime-based tomography for turbid media SO OPTICS LETTERS LA English DT Article ID TISSUE AB Received June 27, 2005; revised manuscript received August 17, 2005; accepted August 18, 2005 We derive a novel algorithm to recover the in vivo distributions of fluorophores based on an asymptotic lifetime analysis of time-domain fluorescence measurements with turbid tissue. We experimentally demonstrate the advantage offered by this method in localizing fluorophores with distinct lifetimes. This algorithm has wide applicability for diagnostic fluorescence imaging in the presence of several-centimeter-thick biological tissue, since fluorescence lifetime is a sensitive indicator of local tissue environment and interactions at the molecular level. (c) 2005 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu RI Dunn, Andrew/I-9527-2014 FU NCRR NIH HHS [P41-RR14075] NR 13 TC 67 Z9 69 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD DEC 15 PY 2005 VL 30 IS 24 BP 3347 EP 3349 DI 10.1364/OL.30.003347 PG 3 WC Optics SC Optics GA 991PX UT WOS:000233827000029 PM 16389827 ER PT J AU Tsao, JCI Dobalian, A Stein, JA AF Tsao, JCI Dobalian, A Stein, JA TI Illness burden mediates the relationship between pain and illicit drug use in persons living with HIV SO PAIN LA English DT Article DE pain; substance use; illicit drug use; HIV; AIDS ID AMBULATORY AIDS PATIENTS; NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; QUALITY-OF-LIFE; SERVICES UTILIZATION; UNITED-STATES; INFECTED INDIVIDUALS; SUBSTANCE-ABUSE; HEALTH SURVEY; DISORDERS AB We investigated predictive and concurrent relationships among reported pain, HIV/AIDS illness burden, and substance use history in 2267 participants in the longitudinal HIV Cost and Services Utilization Study (HCSUS). Substance use history was classified as screening positive for current illicit drug use (N = 253), past drug use (N = 617), and non-user (N = 1397) at baseline. To control for demographic correlates, age, sex and socioeconomic status (SES) were included as predictors. Covariance structure models indicated greater pain at baseline among participants acknowledging current substance use. Pain at baseline was also directly predicted by greater HIV/AIDS illness burden, lower SES, and older age. At 6 months, pain was directly predicted by prior pain, worse concurrent HIV/AIDS illness burden and female sex. At 12 months, pain was predicted by older age, prior pain, and concurrent HIV/AIDS illness. It was also modestly but significantly predicted by current substance use at baseline. In addition to the direct effects on pain, there were significant indirect effects of demographic and drug use variables on pain mediated through HIV/AIDS illness burden and prior pain. There were significant and positive indirect effects of current and past drug use, greater age, and lower SES on pain at all three time periods. Pain at 6 months and pain at 12 months were also indirectly impacted by previous illness burden. Our results indicate that HIV+persons who screened positive for current use of a range of illicit substances experienced greater HIV/AIDS illness burden which in turn predicted increased pain. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Pediat Pain Program, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv,Ctr Excellence Study Healthcare Pro, VA Greater Los Angeles Healthcare Syst HSR&D, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Tsao, JCI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Pediat Pain Program, Dept Pediat, 10940 Wilshire Blvd,Suite 1450, Los Angeles, CA 90024 USA. EM jtsao@mednet.ucla.edu FU AHRQ HHS [U01HS08578, U01 HS008578]; NIDA NIH HHS [DA01070, P01 DA001070, DA017026, R03 DA017026] NR 42 TC 17 Z9 18 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 15 PY 2005 VL 119 IS 1-3 BP 124 EP 132 DI 10.1016/j.pain.2005.09.023 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 998YN UT WOS:000234355900014 PM 16297562 ER PT J AU Gurrera, RJ Dickey, CC Niznikiewicz, MA Voglmaier, MM Shenton, ME McCarley, RW AF Gurrera, RJ Dickey, CC Niznikiewicz, MA Voglmaier, MM Shenton, ME McCarley, RW TI The five-factor model in schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizotypal personality disorder; five-factor model; openness; gender ID SCHIZOPHRENIA; INTELLIGENCE; COMMUNITY; TRAITS; WOMEN AB Studies of the five-factor model of personality in schizotypal personality disorder (SPD) have produced inconsistent results, particularly with respect to openness. In the present study, the NEO-FFI was used to measure five-factor personality dimensions in 28 community volunteers with SPD and 24 psychiatrically healthy individuals. Standard multivariate statistical analyses were used to evaluate personality differences as a function of diagnosis and gender. Individuals with SPD had significantly higher levels of neuroticism and significantly lower levels of extraversion, agreeableness and conscientiousness than those without SPD. Female, but not mate, SPD subjects had significantly higher openness levels than their healthy counterparts, and this gender-specific group difference persisted when SPD symptom severity was statistically controlled. These findings suggest that gender-associated differences in openness may account for prior inconsistent findings regarding this dimension, and they further underscore the importance of examining gender effects in future studies of SPD. (c) 2005 Elsevier B.V. All rights reserved. C1 VA Boston Healthcare Syst, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA 02139 USA. RP Gurrera, RJ (reprint author), VA Boston Healthcare Syst, 940 Belmont St 116A, Brockton, MA 02301 USA. EM ronald_gurrera@hms.harvard.edu; chandlee_dickey@hms.harvard.edu; margaret_niznikiewicz@hms.harvard.edu; martina_voglmaier@hms.harvard.edu; martha_shenton@hms.harvard.edu; robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [K02 MH001110, K02 MH001110-10, MH R01 52801, MH001110] NR 32 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2005 VL 80 IS 2-3 BP 243 EP 251 DI 10.1016/j.schres.2005.08.002 PG 9 WC Psychiatry SC Psychiatry GA 004MT UT WOS:000234757600011 PM 16168625 ER PT J AU Park, Y Hunter, DJ Spiegelman, D Bergkvist, L Berrino, F van den Brandt, PA Buring, JE Colditz, GA Freudenheim, JL Fuchs, CS Giovannucci, E Goldbohm, RA Graham, S Harnack, L Hartman, AM Jacobs, DR Kato, I Krogh, V Leitzmann, MF McCullough, ML Miller, AB Pietinen, P Rohan, TE Schatzkin, A Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Smith-Warner, SA AF Park, Y Hunter, DJ Spiegelman, D Bergkvist, L Berrino, F van den Brandt, PA Buring, JE Colditz, GA Freudenheim, JL Fuchs, CS Giovannucci, E Goldbohm, RA Graham, S Harnack, L Hartman, AM Jacobs, DR Kato, I Krogh, V Leitzmann, MF McCullough, ML Miller, AB Pietinen, P Rohan, TE Schatzkin, A Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Smith-Warner, SA TI Dietary fiber intake and risk of colorectal cancer - A pooled analysis of prospective cohort studies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; SCALE PROSPECTIVE COHORT; WOMENS HEALTH; COLON-CANCER; REGRESSION-MODELS; RANDOMIZED TRIAL; LOW-FAT; REPRODUCIBILITY; RECURRENCE; ADENOMA AB Context Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. Main Outcome Measure Incident colorectal cancer. Results During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR=0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR=0.94; 95% Cl, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% Cl, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% Cl, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% Cl, 0.90-1.11) for colon cancer and 0.85 (95% Cl, 0.72-1.01) for rectal cancer (P for common effects by tumor site=.07). Conclusions In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden. Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. Natl Canc Inst, Epidemiol Unit, I-20133 Milan, Italy. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. TNO, Nutr & Food Res Inst, Dept Epidemiol, NL-3700 AJ Zeist, Netherlands. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Wayne State Univ, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48202 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. NYU, Dept Environm Med, New York, NY 10016 USA. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Krogh, Vittorio/K-2628-2016; Colditz, Graham/A-3963-2009; OI Krogh, Vittorio/0000-0003-0122-8624; Colditz, Graham/0000-0002-7307-0291; Park, Yikyung/0000-0002-6281-489X FU NCI NIH HHS [CA55075, CA78548] NR 51 TC 223 Z9 238 U1 5 U2 32 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 DEC 14 PY 2005 VL 294 IS 22 BP 2849 EP 2857 DI 10.1001/jama.294.22.2849 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 991PU UT WOS:000233826700025 PM 16352792 ER PT J AU Allchorne, AJ Broom, DC Woolf, CJ AF Allchorne, Andrew J. Broom, Daniel C. Woolf, Clifford J. TI Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats SO MOLECULAR PAIN LA English DT Article AB Background: Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain ( cold allodynia). To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results: We demonstrate that a Peltier-cooled cold plate with +/- 1 degrees C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naive rats the threshold for eliciting cold pain behavior is 5 degrees C. The withdrawal threshold for cold allodynia is 15 degrees C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naive rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion: The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Neurogen Corp, Branford, CT 06405 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, 13th St,Bldg 149,4309, Charlestown, MA 02129 USA. EM andrew.allchorne@gmail.com; dbroom@nrgn.com; cwoolf@partners.org FU NINDS NIH HHS [R01 NS039518, NS38253, NS039518, R37 NS039518, R01 NS038253] NR 26 TC 61 Z9 64 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD DEC 14 PY 2005 VL 1 AR 36 DI 10.1186/1744-8069-1-36 PG 9 WC Neurosciences SC Neurosciences & Neurology GA V43NW UT WOS:000202942800001 PM 16354295 ER PT J AU Shin, JM Grundler, G Senn-Bilfinger, J Simon, WA Sachs, G AF Shin, JM Grundler, G Senn-Bilfinger, J Simon, WA Sachs, G TI Functional consequences of the oligomeric form of the membrane-bound gastric H,K-ATPase SO BIOCHEMISTRY LA English DT Article ID K+-COMPETITIVE INHIBITOR; PROTON PUMP INHIBITORS; SUBSTITUTED IMIDAZO<1,2-A>PYRIDINES; ANTIULCER AGENTS; SARCOPLASMIC-RETICULUM; ADENOSINE-TRIPHOSPHATASE; CATALYTIC CYCLE; H+/K+-ATPASE; BINDING-SITE; BETA-SUBUNIT AB Cross-linking and two-dimensional crystallization studies have suggested that the membrane-bound gastric H,K-ATPase might be a dimeric alpha,beta-heterodimer. Effects of an oligomeric structure on the characteristics of E-1, E-2, and phosphoenzyme conformations were examined by measuring binding stoichiometries of acid-stable phosphorylation (EP) from [gamma-P-32]ATP or (32)p(i) or of binding of [gamma-P-32]ATP and of a K+-competitive imidazonaphthyridine (INT) inhibitor to an enzyme preparation containing similar to 5 nmol of ATPase/mg of protein. At < 10 mu M MgATP, E-1 [ATP]center dot Mg center dot(H+):E-2 is formed at a high-affinity site, and is then converted to E1P center dot Mg center dot(H+):E-2 and then to E2P center dot Mg:E-1 with luminal proon extrusion. Maximal acid-stable phosphorylation yielded 2.65 nmol/mg of protein. Luminal K+-dependent dephosphorylation returns this conformation to the E, form. At high MgATP concentrations (> 0.1 mM), the oligomer forms E2P center dot Mg:E,[ATP]center dot Mg center dot(H+). The sum of the levels of maximal EP formation and ATP binding was 5.3 nmol/mg. The maximal amount of [H-3]INT bound was 2.6 nmol/mg in the presence of MuATP, Mg2+, Mg-P-i, or Mg-vanadate with complete inhibition of activity. K+ displaced INT only in nigericin-treated vesicles, and thus, INT binds to the luminal surface of the E2 form. INT-bound enzyme also formed 2.6 nmol of EP/mg at high ATP concentrations by formation of E-2 center dot Mg center dot(INT)(exo):E-1[ATP]center dot Mg center dot(H+) which is converted to E-2 center dot Mg center dot(INT)(exo):E1P center dot Mg center dot(H+)(cyto), but this E1P form was K+-insensitive.Bindina of the inhibitor fixes half the oligomer in the E2 form with full inhibition of activity, while the other half of the oligomer is able to form E1P only when the inhibitor is bound. It appears that the catalytic subunits of the oligomer during turnover in intact gastric vesicles are restricted to a reciprocal E-1:E-2 configuration. C1 VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. ALTANA Pharma AG, Constance, Germany. RP VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM jaishin@ucla.edu FU NIDDK NIH HHS [DK58333, DK17294, DK46917, DK53462] NR 66 TC 17 Z9 18 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 13 PY 2005 VL 44 IS 49 BP 16321 EP 16332 DI 10.1021/bi051342q PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992QH UT WOS:000233898400039 PM 16331993 ER PT J AU Pfeifer, HH Thiele, EA AF Pfeifer, HH Thiele, EA TI Low-glycemic-index treatment: A liberalized ketogenic diet for treatment of intractable epilepsy SO NEUROLOGY LA English DT Article ID EFFICACY; BRAIN AB The ketogenic diet is often effective for intractable epilepsy, but many patients have trouble complying with the strict regimen. The authors tested an alternative diet regimen, a low-glycemic-index treatment, with more liberal total carbohydrate intake but restricted to foods that produce relatively little increase in blood glucose (glycemic index < 50). Ten of 20 patients treated with this regimen experienced a greater than 90% reduction in seizure frequency. C1 Massachusetts Gen Hosp, Pediat Epilepsy Serv, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Serv, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 10 TC 107 Z9 114 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 13 PY 2005 VL 65 IS 11 BP 1810 EP 1812 DI 10.1212/01.wnl.0000187071.24292.9e PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 992QG UT WOS:000233898300028 PM 16344529 ER PT J AU Karamohamed, S Latourelle, JC Racette, BA Perlmutter, JS Wooten, GF Lew, M Klein, C Shill, H Golbe, LI Mark, MH Guttman, M Nicholson, G Wilk, JB Saint-Hilaire, M DeStefano, L Prakash, R Tobin, S Williamson, J Suchowersky, O Labell, N Growdon, BNJ Singer, C Watts, R Goldwurm, S Pezzoli, G Baker, KB Giroux, ML Pramstaller, PP Burn, DJ Chinnery, P Sherman, S Vieregge, P Litvan, I Gusella, JF Myers, RH Parsian, A AF Karamohamed, S Latourelle, JC Racette, BA Perlmutter, JS Wooten, GF Lew, M Klein, C Shill, H Golbe, LI Mark, MH Guttman, M Nicholson, G Wilk, JB Saint-Hilaire, M DeStefano, L Prakash, R Tobin, S Williamson, J Suchowersky, O Labell, N Growdon, BNJ Singer, C Watts, R Goldwurm, S Pezzoli, G Baker, KB Giroux, ML Pramstaller, PP Burn, DJ Chinnery, P Sherman, S Vieregge, P Litvan, I Gusella, JF Myers, RH Parsian, A TI BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD study SO NEUROLOGY LA English DT Article ID NEUROTROPHIC FACTOR; POLYMORPHISM AB Brain-derived neurotrophic factor ( BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Virginia, Hlth Syst, Dept Neurol, Charlottesville, VA 22908 USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Barrow Neurol Inst, Muhammad Ali Parkinson Res Ctr, Phoenix, AZ 85013 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Sydney, Concord Hosp, ANZAC Res Inst, Dept Neurol, Sydney, NSW 2006, Australia. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Human Genet Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit,Ctr Human Genet Res, Boston, MA 02115 USA. Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy. Ist Clin Perfezionamento, Med Genet Unit, Milan, Italy. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Gen Reg Hosp Bolzano, Dept Neurol, Bolazno, Italy. Newcastle Gen Hosp, Reg Neurosci Ctr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Arizona, Dept Neurol, Tucson, AZ USA. Klinikum Lippe Lemgo, Neurol Klin, Lemgo, Germany. Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA. Univ Arkansas Med Sci, Dept Pediat, Human Genom Labs, Little Rock, AR 72202 USA. RP Parsian, A (reprint author), Univ Arkansas Med Sci, Res Inst, Coll Med, Arkansas Childrens Hosp, 1120 Marshall St, Little Rock, AR 72202 USA. EM ParsianAbbas@uams.edu RI Pramstaller, Peter/C-2357-2008; Goldwurm, Stefano/Q-8978-2016; OI Goldwurm, Stefano/0000-0002-1651-567X; Litvan, Irene/0000-0002-3485-3445 FU NINDS NIH HHS [R01 NS36711-05]; Telethon [GTF04007] NR 10 TC 45 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 13 PY 2005 VL 65 IS 11 BP 1823 EP 1825 DI 10.1212/01.wnl.0000187075.81589.fd PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 992QG UT WOS:000233898300033 PM 16344533 ER PT J AU Ferrante, KL Shefner, J Zhang, H Betensky, R O'Brien, M Yu, H Fantasia, M Taft, J Beal, MF Traynor, B Newhall, K Donofrio, P Caress, J Ashburn, C Freiberg, B O'Neill, C Paladenech, C Walker, T Pestronk, A Abrams, B Florence, J Renna, R Schierbecker, J Malkus, B Cudkowicz, M AF Ferrante, KL Shefner, J Zhang, H Betensky, R O'Brien, M Yu, H Fantasia, M Taft, J Beal, MF Traynor, B Newhall, K Donofrio, P Caress, J Ashburn, C Freiberg, B O'Neill, C Paladenech, C Walker, T Pestronk, A Abrams, B Florence, J Renna, R Schierbecker, J Malkus, B Cudkowicz, M TI Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; Q(10); MITOCHONDRIA; DISEASE AB An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat,Dept Biostat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10021 USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27109 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Ferrante, KL (reprint author), Massachusetts Gen Hosp, 13th St,CNY 149,Room 2274, Charlestown, MA 02129 USA. EM kimberly.ferrante@umassmed.edu RI Traynor, Bryan/G-5690-2010; OI Ferrante, Kimberly/0000-0002-6069-9226; Caress, James/0000-0002-5814-6083 FU NCRR NIH HHS [M01-RR-01066, M01-RR00036, M01-RR07122] NR 9 TC 102 Z9 107 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 13 PY 2005 VL 65 IS 11 BP 1834 EP 1836 DI 10.1212/01.wnl.0000187070.35365.d7 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 992QG UT WOS:000233898300037 PM 16344537 ER PT J AU Lee, JW Wilck, M Venna, N AF Lee, JW Wilck, M Venna, N TI Dementia due to neurosyphilis with persistently negative CSFVDRL SO NEUROLOGY LA English DT Editorial Material ID TREPONEMAL ANTIBODY; PALLIDUM; TESTS C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. RP Lee, JW (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM jlee38@partners.org NR 6 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 13 PY 2005 VL 65 IS 11 BP 1838 EP 1838 DI 10.1212/01.wnl.0000187082.92497.95 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 992QG UT WOS:000233898300039 PM 16344539 ER PT J AU Kobayashi, T Lyons, KM McMahon, AP Kronenberg, HM AF Kobayashi, T Lyons, KM McMahon, AP Kronenberg, HM TI BMP signaling stimulates cellular differentiation at multiple steps during cartilage development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone morphogenetic protein receptor 1A; bone morphogenetic protein receptor 1B; bone morphogenetic protein; chondrocyte differentiation; transgenic ID BONE MORPHOGENETIC PROTEIN; GROWTH-PLATE CHONDROCYTES; HORMONE-RELATED PEPTIDE; INDIAN HEDGEHOG; MOUSE LIMB; PARATHYROID-HORMONE; GENE-EXPRESSION; CHICK LIMB; CHONDROGENESIS; RECEPTORS AB Bone morphogenetic proteins (BMPs) play important roles at multiple stages of endochondral bone formation. However, the roles of BMP signaling in chondrocytes in vivo are still contentious. In the present study, we overexpressed a constitutively active BMP receptor 1A (caBmpr1a) in chondrocytes by using two systems: caBmpr1a was directly driven by a rat type II collagen promoter in a conventional transgenic system and indirectly driven in a UAS-Gal4 binary system. CaBmpr1a expression caused shortening of the columnar layer of proliferating chondrocytes and up-regulation of maturation markers, suggesting acceleration of differentiation of proliferating chondrocytes toward hypertrophic chondrocytes. In addition to the acceleration of chondrocyte differentiation, conventional transgenic mice showed widening of cartilage elements and morphological alteration of perichondrial cells, possibly due to stimulation of differentiation of prechondrogenic cells. Moreover, bigenic expression of caBmpr1a rescued the differentiation defect of prechondrogenic cells in Bmpr1b-null phalanges. This finding indicates that BMP signaling is necessary for phalangeal prechondrogenic cells to differentiate into chondrocytes and that signaling of BMP receptor 1B in this context is replaceable by that of a constitutively active BMP receptor 1A. These results suggest that BMP signaling in prechondrogenic cells and in growth plate chondrocytes stimulates their chondrocytic differentiation and maturation toward hypertrophy, respectively. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org RI Lyons, Karen/P-1843-2014 OI Lyons, Karen/0000-0001-9420-5813 FU NIAMS NIH HHS [AR44528, R01 AR044528]; NIDDK NIH HHS [P01 DK056246, P01 DK56246] NR 35 TC 88 Z9 96 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 DEC 13 PY 2005 VL 102 IS 50 BP 18023 EP 18027 DI 10.1073/pnas.0503617102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 994DL UT WOS:000234010500027 PM 16322106 ER PT J AU Arinobu, Y Iwasaki, H Gurish, MF Mizuno, S Shigematsu, H Ozawa, H Tenen, DG Austen, KF Akashi, K AF Arinobu, Y Iwasaki, H Gurish, MF Mizuno, S Shigematsu, H Ozawa, H Tenen, DG Austen, KF Akashi, K TI Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE integrin; progenitor; CCAAT/enhancer-binding protein ID COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; MAST-CELLS; TRICHINELLA-SPIRALIS; MESSENGER-RNA; STEM-CELLS; PROGENITORS; IDENTIFICATION; MICE; ABSENCE AB Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the beta 7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil/mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells. We also identified the basophil progenitor (Ball) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT/enhancer-binding protein alpha (C/EBP alpha) plays a primary role in the fate decision of BMCPs, being expressed in BaPs but not in MCPs. Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C/EBP alpha. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. Kyushu Univ, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM koichi_akashi@dfci.harvard.edu OI Tenen, Daniel/0000-0002-6423-3888 FU NHLBI NIH HHS [HL036110, HL56745, P01 HL036110, R01 HL056745]; NIAID NIH HHS [P01 AI031599, AI031599, AI063284, R01 AI063284, U19 AI031599]; NIDDK NIH HHS [DK061320, R01 DK061320] NR 35 TC 167 Z9 176 U1 1 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 13 PY 2005 VL 102 IS 50 BP 18105 EP 18110 DI 10.1073/pnas.0509148102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 994DL UT WOS:000234010500041 PM 16330751 ER PT J AU Lee, SJ Reed, LA Davies, MV Girgenrath, S Goad, MEP Tomkinson, KN Wright, JF Barker, C Ehrmantraut, G Holmstrom, J Trowell, B Gertz, B Jiang, MS Sebald, SM Matzuk, M Li, E Liang, LF Quattlebaum, E Stotish, RL Wolfman, NM AF Lee, SJ Reed, LA Davies, MV Girgenrath, S Goad, MEP Tomkinson, KN Wright, JF Barker, C Ehrmantraut, G Holmstrom, J Trowell, B Gertz, B Jiang, MS Sebald, SM Matzuk, M Li, E Liang, LF Quattlebaum, E Stotish, RL Wolfman, NM TI Regulation of muscle growth by multiple ligands signaling through activin type II receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE myostatin; TGF-beta ID BETA SUPERFAMILY; MYOSTATIN GENE; MICE; CATTLE; DIFFERENTIATION; MUTATIONS; MOUSE; GDF11; MASS; CELL AB Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn(-/-) mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Wyeth Exploratory Drug Safety, Andover, MA 01810 USA. Wyeth Discovery Res, Antibody Technol Grp, Cambridge, MA 02140 USA. Wyeth Discovery Res, Dept Cardiovasc & Metab Dis, Cambridge, MA 02140 USA. Wyeth Discovery Res, Dept Inflammat, Cambridge, MA 02140 USA. MetaMorphix Canada, Saskatoon, SK S7N 3R2, Canada. MetaMorphix Inc, Beltsville, MD 20705 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Cambridge, MA 02139 USA. RP Lee, SJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 725 N Wolfe St,PCTB 803, Baltimore, MD 21205 USA. EM silee@jhmi.edu FU NCI NIH HHS [R01 CA088866, R01CA88866]; NICHD NIH HHS [R01HD32067, R01 HD032067, R01 HD035887, R01HD35887] NR 30 TC 269 Z9 283 U1 0 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 DEC 13 PY 2005 VL 102 IS 50 BP 18117 EP 18122 DI 10.1073/pnas.0505996102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 994DL UT WOS:000234010500043 PM 16330774 ER PT J AU Buffo, A Vosko, MR Erturk, D Hamann, GF Jucker, M Rowitch, D Gotz, M AF Buffo, A Vosko, MR Erturk, D Hamann, GF Jucker, M Rowitch, D Gotz, M TI Expression pattern of the transcription factor Olig2 in response to brain injuries: Implications for neuronal repair SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid; gliosis; mouse neocortex; pax6; stab wound ID CENTRAL-NERVOUS-SYSTEM; ADULT MAMMALIAN BRAIN; RADIAL GLIAL-CELLS; RAT SPINAL-CORD; SUBVENTRICULAR ZONE; PROGENITOR CELLS; PRECURSOR CELLS; STEM-CELLS; NEUROGENESIS; ASTROCYTES AB Despite the presence of neural stem cells and ongoing neurogenesis in some regions of the adult mammalian brain, neurons are not replaced in most brain regions after injury. With the aim to unravel factors contributing to the failure of neurogenesis in the injured cerebral cortex, we examined the expression of cell fate determinants after acute brain injuries, such as stab wound or focal ischemia, and in a model of chronic amyloid deposition. Although none of the neurogenic factors, such as Pax6, Mash1, Ngn2, was detected in the injured parenchyma, we observed a strong up-regulation of the bHLH transcription factor Olig2, but not Olig1, upon acute and chronic injury. To examine the function of Olig2 in brain lesion, we injected retroviral vectors containing a dominant negative form of Olig2 into the lesioned cortex 2 days after a stab wound. Antagonizing Olig2 function resulted in a significant number of infected cells generating immature neurons that were not observed after injection of the control virus. These data, therefore, imply Olig2 as a repressor of neurogenesis in cells reacting to brain injury and open innovative perspectives toward evoking endogenous neuronal repair. C1 Natl Res Ctr Environm & Hlth, Inst Stem Cell Res, D-87564 Munich, Germany. Univ Turin, Dept Neurosci, I-10125 Turin, Italy. Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81377 Munich, Germany. Dr Horst Schmidt Klin, Dept Neurol, D-65199 Wiesbaden, Germany. Hertie Inst Clin Brain Res, Dept Cellular Neurol, D-72076 Tubingen, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Munich, Dept Physiol, D-80336 Munich, Germany. RP Buffo, A (reprint author), Natl Res Ctr Environm & Hlth, Inst Stem Cell Res, Ingolstadter Landstr 1, D-87564 Munich, Germany. EM annalisa.buffo@gsf.de; magdalena.goetz@gsf.de OI Buffo, Annalisa/0000-0001-7637-0006 NR 53 TC 202 Z9 211 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 DEC 13 PY 2005 VL 102 IS 50 BP 18183 EP 18188 DI 10.1073/pnas.0506535102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 994DL UT WOS:000234010500054 PM 16330768 ER PT J AU Gopal, R Glasheen, JJ Miyoshi, TJ Prochazka, AV AF Gopal, R Glasheen, JJ Miyoshi, TJ Prochazka, AV TI Burnout and internal medicine resident work-hour restrictions SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FAMILY-PRACTICE RESIDENTS; PATIENT-CARE; STRESS; SLEEP AB Background: Burnout is very common in internal medicine residents. Effective July 2003, all residents were restricted to work less than an average of 80 hours per week and no more than 30 hours of continuous duty for patient care and educational obligations. We evaluated rates of burn-out in internal medicine residents before and after the implementation of the new work-hour restriction. Methods: University of Colorado Health Science Center internal medicine residents were surveyed in May 2003 and May 2004. The survey contained the Maslach Burnout Inventory, organized into 3 subscales (ie, emotional exhaustion, depersonalization, and personal accomplishment); the Primary Care Evaluation of Mental Disorders depression screen; and self-reported quality of care and education. Results: The response rate was 87% (121 of 139 residents) and 74% (106 of 143 residents) in 2003 and 2004, respectively. Self-reported hours worked decreased from a mean of 74.6 to 67.1 (P=.003). In 2004, 13% fewer residents experienced high emotional exhaustion (42% vs 29%; P=.03). There was a trend toward fewer residents with high depersonalization (61% vs 55%; P=.13) and fewer residents with a positive depression screen (51% vs 41%; P=.11). Personal accomplishment did not change. The assessment of self-reported quality of care did not significantly change from 2003 to 2004. Residents reported attending fewer educational conferences per month (18.99 vs 15.56; P=.01). Overall residency satisfaction decreased 6 mm on a 100-mm visual analogue score (P=.02). Conclusions: Burnout continues to be a major problem. Reducing hours may be the first step to reduce burnout but may also affect education and quality of care. C1 Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Dept Internal Med, Aurora, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Aurora, CO USA. RP Gopal, R (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Box 11B,1055 Clermont St, Denver, CO 80220 USA. EM Ravi.Gopal@med.va.gov NR 30 TC 132 Z9 136 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 12 PY 2005 VL 165 IS 22 BP 2595 EP 2600 DI 10.1001/archinte.165.22.2595 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800010 PM 16344416 ER PT J AU Jagsi, R Kitch, BT Weinstein, DF Campbell, EG Hutter, M Weissman, JS AF Jagsi, R Kitch, BT Weinstein, DF Campbell, EG Hutter, M Weissman, JS TI Residents report on adverse events and their causes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL ERRORS; PATIENT SAFETY; WORK HOURS; HOSPITALIZED-PATIENTS; INTENSIVE-CARE; UNITED-STATES; COLORADO; INTERNS; QUALITY; UTAH AB Background: Resident physicians are frontline providers with a unique vantage point from which to comment on patient safety-related events. Methods: We surveyed trainees at 2 teaching hospitals about experiences with adverse events (AEs), mistakes, and near misses, as well as the potential causes. Results: Responses were obtained from 821 (57%) of 1440 eligible trainees. Analysis was restricted to 689 clinical trainees. More than half (55%) reported ever caring for a patient who had an AE. The most common types of AEs were procedural and medication related. More than two thirds of AEs were considered significant. Of the most recent AEs, 24% were attributed to mistakes. The most common reasons for mistakes, as perceived by residents, were excessive work hours (19%), inadequate supervision (20%), and problems with handoffs (15%). In the last week, 114 respondents (18%) reported having a patient with an AE; of these, 42 (37%) reported AEs involving a mistake for which they considered themselves responsible. In addition, 141 (23%) reported near-miss incidents in the last week for which they considered themselves responsible, In multivariate analyses, significant predictors of AEs in the last week were inpatient rotation, duty hours in the last week, and procedural specialty. Predictors of near-miss errors in the last week were inpatient rotation, days of fatigue in the last month, and postgraduate year I status. Conclusions: These findings support the perception that AEs are commonly encountered by physicians and often associated with errors. Causes of errors in teaching hospitals appear to be multifactorial, and a variety of measures are necessary to improve safety. Eliciting residents' perspectives is important because residents may perceive events, actions, and causal relationships that medical record reviewers or observers cannot. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Partners HealthCare Syst, Off Grad Med Educ, Boston, MA 02114 USA. RP Jagsi, R (reprint author), Partners HealthCare Syst, Off Grad Med Educ, Bulfinch 2,55 Fruit St, Boston, MA 02114 USA. EM rjagsi@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 42 TC 124 Z9 126 U1 3 U2 7 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 DEC 12 PY 2005 VL 165 IS 22 BP 2607 EP 2613 DI 10.1001/archinte.165.22.2607 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800012 PM 16344418 ER PT J AU Hesse, BW Nelson, DE Kreps, GL Croyle, RT Arora, NK Rimer, BK Viswanath, K AF Hesse, BW Nelson, DE Kreps, GL Croyle, RT Arora, NK Rimer, BK Viswanath, K TI Trust and sources of health information - The impact of the Internet and its implications for health care providers: Findings from the first Health Information National Trends Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL INFORMATION; CANCER-PATIENTS; COMMUNICATION; QUALITY; TELEMEDICINE; COMMUNITIES; PHYSICIANS; SUPPORT; SYSTEMS; CANADA AB Background: The context in which patients consume health information has changed dramatically with diffusion of the Internet, advances in telemedicine, and changes in media health coverage. The objective of this study was to provide nationally representative estimates for health-related uses of the Internet, level of trust in health information sources, and preferences for cancer information sources. Methods: Data from the Health Information National Trends Survey were used. A total of 6369 persons 18 years or older were studied. The main outcome measures were online health activities, levels of trust, and source preference. Results: Analyses indicated that 63.0% (95% confidence interval [CI], 61.7%-64.3%) of the US adult population in 2003 reported ever going online, with 63.7% (95% Cl, 61.7%-65.8%) of the online population having looked for health information for themselves or others at least once in the previous 12 months. Despite newly available communication channels, physicians remained the most highly trusted information source to patients, with 62.4% (95% Cl, 60.8%-64.0%) of adults expressing a lot of trust in their physicians. When asked where they preferred going for specific health information, 49.5% (95% Cl, 48.1%-50.8%) reported wanting to go to their physicians first. When asked where they actually went, 48.6% (95% Cl, 46.1%-5 1.0%) reported going online first, with only 10.9% (95% Cl, 9.5%-12.3%) going to their physicians first. Conclusion: The Health Information National Trends Survey data portray a tectonic shift in the ways in which patients consume health and medical information, with more patients looking for information online before talking with their physicians. C1 NCI, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Harvard Univ, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hesse, BW (reprint author), NCI, 6130 Execut Blvd,Mail Stop Code 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 56 TC 532 Z9 536 U1 7 U2 102 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 DEC 12 PY 2005 VL 165 IS 22 BP 2618 EP 2624 DI 10.1001/archinte.165.22.2618 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800013 PM 16344419 ER PT J AU Frayne, SM Halanych, JH Miller, DR Wang, F Lin, H Pogach, L Sharkansky, EJ Keane, TM Skinner, KM Rosen, CS Berlowitz, DR AF Frayne, SM Halanych, JH Miller, DR Wang, F Lin, H Pogach, L Sharkansky, EJ Keane, TM Skinner, KM Rosen, CS Berlowitz, DR TI Disparities in diabetes care - Impact of mental illness SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OF-VETERANS-AFFAIRS; ACUTE MYOCARDIAL-INFARCTION; PLACEBO-CONTROLLED TRIAL; POOR GLYCEMIC CONTROL; HEALTH-CARE; EXCESS MORTALITY; MEDICAL-CARE; PSYCHIATRIC-DISORDERS; GENDER DIFFERENCES; DOUBLE-BLIND AB Background: Emerging evidence indicates that patients with mental health conditions (MHCs) may receive less intensive medical care. Diabetes serves as a useful condition in which to test for MHC-related disparities in care. We examined whether quality measures for diabetes care are worse for patients with or without MHCs. Methods: This national, cross-sectional study included 313 586 noninstitutionalized Veterans Health Administration patients with diabetes (identified from diagnostic codes and prescriptions) whose Veterans Health Administration facility transmitted laboratory data to a central database; 76 799 (25%) had MHCs (based on diagnostic codes for depressed mood, anxiety, psychosis, manic symptoms, substance use disorders, personality disorders, and other categories). National data from Veterans Health Administration records, Medicare claims, and a national survey were linked to characterize 1999 diabetes care. Results: Failure to meet diabetes performance measures was more common in patients with MHCs: unadjusted odds ratio (95% confidence interval) was 1.24 (1.22-1.27) for no hemoglobin A, testing, 1.25 (1.23-1.28) for no low-density lipoprotein cholesterol testing, 1.05 (1.03-1.07) for no eye examination, 1.32 (1.30-1.35) for poor glycemic control, and 1.17(1.15-1.20) for poor lipemic control. Disparities persisted after case mix adjustment and were more pronounced with specific MHCs (psychotic, manic, substance use, and personality disorders). The percentage not meeting diabetes care standards increased with increasing number of MHCs. Conclusion: Patients with mental illness merit special attention in national diabetes quality improvement efforts. C1 Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. Stanford Univ, Sch Med, Div Gen Internal Med, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL 35294 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. VA New Jersey Healthcare Syst, Ctr Healthcare Knowledge Management, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. RP Frayne, SM (reprint author), Ctr Hlth Care Evaluat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM sfrayne@stanford.edu NR 65 TC 164 Z9 169 U1 13 U2 23 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 DEC 12 PY 2005 VL 165 IS 22 BP 2631 EP 2638 DI 10.1001/archinte.165.22.2631 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800015 PM 16344421 ER PT J AU O'Hare, AM Newman, AB Katz, R Fried, LF Stehman-Breen, CO Seliger, SL Siscovick, DS Shlipak, MG AF O'Hare, AM Newman, AB Katz, R Fried, LF Stehman-Breen, CO Seliger, SL Siscovick, DS Shlipak, MG TI Cystatin C and incident peripheral arterial disease events in the elderly - Results from the cardiovascular health study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RENAL-INSUFFICIENCY; HEART-FAILURE; RISK; MORTALITY; PREVALENCE; MARKER; IMPACT; INDIVIDUALS; CREATININE AB Background: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined. Methods: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR). Results: The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (> 1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses. Conclusion: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients. C1 Vet Affairs Med Ctr, Div Nephrol, Dept Med, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98195 USA. RP O'Hare, AM (reprint author), Vet Affairs Med Ctr, Div Nephrol, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM Ann.O'Hare@med.va.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01 HC 15103, N01 HC 35129, N01 HC 85079, N01 HC 85080, N01 HC 85081, N01 HC 85082, N01 HC 85083, N01 HC 85084, N01 HC 85085, N01 HC 85086, R01 HL 073208-01] NR 25 TC 57 Z9 58 U1 0 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 DEC 12 PY 2005 VL 165 IS 22 BP 2666 EP 2670 DI 10.1001/archinte.165.22.2666 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800020 PM 16344426 ER PT J AU Chen, ZQ Kujawa, SG McKenna, MJ Fiering, JO Mescher, MJ Borenstein, JT Swan, EEL Sewell, WF AF Chen, ZQ Kujawa, SG McKenna, MJ Fiering, JO Mescher, MJ Borenstein, JT Swan, EEL Sewell, WF TI Inner ear drug delivery via a reciprocating perfusion system in the guinea pig SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE hearing; deafness; therapy; pharmacology; cochlea ID COCHLEAR GENE-TRANSFER; AUDITORY-NERVE; HAIR CELL; HEARING-LOSS; INTRACOCHLEAR INFUSION; OTOACOUSTIC EMISSIONS; IN-VIVO; NEUROTROPHINS; PROTECTION; MICROPUMP AB Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with well-characterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 mu M), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. MEEI, Dept Otolaryngol, Boston, MA 02114 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC000767, R21 DC04983, P30 DC005209, R01 DC00767, R01 DC003401, R01 DC000767-16A1, R01 DC03401-07] NR 81 TC 48 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD DEC 10 PY 2005 VL 110 IS 1 BP 1 EP 19 DI 10.1016/j.jconrel.2005.09.003 PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 998FV UT WOS:000234304900001 PM 16274830 ER PT J AU Kaelin, WG AF Kaelin, WG TI The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE von Hippel-Lindau; hydroxylation; HIF; kidney cancer; oxygen; hemangioblastoma; pheochromocytoma; EgIN; FIH-1; succinate dehydrogenase ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR PROTEIN; RENAL-CELL-CARCINOMA; UBIQUITIN-PROTEASOME PATHWAY; ISCHEMIA-REPERFUSION INJURY; BIOLOGICALLY-ACTIVE PRODUCT; RECEPTOR INHIBITOR SU5416; PROSTATE-CANCER CELLS; PAS DOMAIN PROTEIN AB The heterodimeric transcription factor HIF (hypoxia-inducible factor), consisting of a labile a-subunit and a stable beta-subunit, is a master regulator of genes involved in acute or chronic adaptation to low oxygen. Studies performed over the past 5 years revealed that HIF alpha-subunits are enzymatically hydroxylated in an oxygen-dependent manner. Hydroxylation of either of two conserved prolyl residues targets HIF alpha. for destruction by a ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein whereas hydroxylation on a C-terminal asparagine affects HIF transactivation function. Pharmacological manipulation of HIF activity might be beneficial in diseases characterized by abnormal tissue oxygenation including myocardical infarction, cerebrovascular disease, and cancer. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu NR 194 TC 138 Z9 143 U1 0 U2 8 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 DEC 9 PY 2005 VL 338 IS 1 BP 627 EP 638 DI 10.1016/j.bbrc.2005.08.165 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 984IO UT WOS:000233296700087 PM 16153592 ER PT J AU Chowdhury, D Keogh, MC Ishii, H Peterson, CL Buratowski, S Lieberman, J AF Chowdhury, D Keogh, MC Ishii, H Peterson, CL Buratowski, S Lieberman, J TI gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair SO MOLECULAR CELL LA English DT Article ID PROTEIN PHOSPHATASE 2A; HISTONE H2AX; DAMAGE RESPONSE; TUMOR-SUPPRESSOR; PHOSPHORYLATION; CHROMATIN; RECRUITMENT; KINASE; MDC1; AUTOPHOSPHORYLATION AB Phosphorylated histone H2AX (gamma-H2AX) forms foci over large chromatin domains surrounding double-stranded DNA breaks (DSB). These foci recruit DSB repair proteins and dissolve during or after repair is completed. How gamma-H2AX is removed from chromatin remains unknown. Here, we show that protein phosphatase 2A (PP2A) is involved in removing gamma-H2AX foci. The PP2A catalytic subunit [PP2A(C)] and gamma-H2AX communoprecipitate and colocalize in DNA damage foci and PP2A dephosphorylates gamma-H2AX in vitro. The recruitment of PP2A(C) to DNA damage foci is H2AX dependent. When PP2A(C) is inhibited or silenced by RNA interference, gamma-H2AX foci persist, DNA repair is inefficient, and cells are hypersensitive to DNA damage. The effect of PP2A on gamma-H2AX levels is independent of ATM, ATR, or DNA-PK activity. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587]; NIGMS NIH HHS [R01 GM054096] NR 43 TC 299 Z9 313 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 9 PY 2005 VL 20 IS 5 BP 801 EP 809 DI 10.1016/j.molcel.2005.10.003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994LN UT WOS:000234033400017 PM 16310392 ER PT J AU Shaw, RJ Lamia, KA Vasquez, D Koo, SH Bardeesy, N DePinho, RA Montminy, M Cantley, LC AF Shaw, RJ Lamia, KA Vasquez, D Koo, SH Bardeesy, N DePinho, RA Montminy, M Cantley, LC TI The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin SO SCIENCE LA English DT Article ID ACTIVATED PROTEIN-KINASE; CREB COACTIVATOR TORC2; HEPATIC GLUCONEOGENESIS; FOOD-INTAKE; SNF1-ACTIVATING KINASES; INSULIN-RESISTANCE; UPSTREAM KINASES; RAT-TISSUES; AMP; PGC-1 AB The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha), which in turn drives gluconeogenesis. Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1 alpha expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the regulation of gluconeogenesis. Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02115 USA. Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon 440746, South Korea. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. RP Shaw, RJ (reprint author), Salk Inst Biol Studies, Mol & Cell Biol Labs, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM shaw@salk.edu RI Cantley, Lewis/D-1800-2014; Koo, Seung-Hoi/E-2763-2015 OI Cantley, Lewis/0000-0002-1298-7653; Koo, Seung-Hoi/0000-0001-8769-2879 FU NCI NIH HHS [CA84313, U01 CA084313]; NIGMS NIH HHS [GM056203, GM37828, R01 GM056203, R01 GM056203-09, R37 GM037828] NR 47 TC 981 Z9 1028 U1 16 U2 101 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 9 PY 2005 VL 310 IS 5754 BP 1642 EP 1646 DI 10.1126/science.1120781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 993NV UT WOS:000233961700035 PM 16308421 ER PT J AU Lindblad-Toh, K Wade, CM Mikkelsen, TS Karlsson, EK Jaffe, DB Kamal, M Clamp, M Chang, JL Kulbokas, EJ Zody, MC Mauceli, E Xie, XH Breen, M Wayne, RK Ostrander, EA Ponting, CP Galibert, F Smith, DR deJong, PJ Kirkness, E Alvarez, P Biagi, T Brockman, W Butler, J Chin, CW Cook, A Cuff, J Daly, MJ DeCaprio, D Gnerre, S Grabherr, M Kellis, M Kleber, M Bardeleben, C Goodstadt, L Heger, A Hitte, C Kim, L Koepfli, KP Parker, HG Pollinger, JP Searle, SMJ Sutter, NB Thomas, R Webber, C Lander, ES AF Lindblad-Toh, K Wade, CM Mikkelsen, TS Karlsson, EK Jaffe, DB Kamal, M Clamp, M Chang, JL Kulbokas, EJ Zody, MC Mauceli, E Xie, XH Breen, M Wayne, RK Ostrander, EA Ponting, CP Galibert, F Smith, DR deJong, PJ Kirkness, E Alvarez, P Biagi, T Brockman, W Butler, J Chin, CW Cook, A Cuff, J Daly, MJ DeCaprio, D Gnerre, S Grabherr, M Kellis, M Kleber, M Bardeleben, C Goodstadt, L Heger, A Hitte, C Kim, L Koepfli, KP Parker, HG Pollinger, JP Searle, SMJ Sutter, NB Thomas, R Webber, C Lander, ES CA Broad Inst Genome Sequencing Plat TI Genome sequence, comparative analysis and haplotype structure of the domestic dog SO NATURE LA English DT Review ID SINGLE NUCLEOTIDE POLYMORPHISMS; MOLECULAR EVOLUTION; LINKAGE DISEQUILIBRIUM; GENE DESERTS; BODY-SIZE; ACCELERATED EVOLUTION; MAMMALIAN EVOLUTION; NONCODING SEQUENCES; CANIS-FAMILIARIS; DNA-SEQUENCES AB Here we report a high-quality draft genome sequence of the domestic dog ( Canis familiaris), together with a dense map of single nucleotide polymorphisms ( SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health. C1 Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Boston Univ, Program Bioinformat, Boston, MA 02215 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Human Anat & Genet, MRC Funct Genet, Oxford OX1 3QX, England. Univ Rennes 1, Fac Med, CNRS, UMR Genet & Dev 6061, F-35043 Rennes, France. Agencourt Biosci Corp, Beverly, MA 01915 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Inst Genom Res, Rockville, MD 20850 USA. Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lindblad-Toh, K (reprint author), Harvard Univ, Broad Inst, 320 Charles St, Cambridge, MA 02141 USA. EM lander@broad.mit.edu RI Mikkelsen, Tarjei/A-1306-2007; Parker, Heidi/C-6954-2008; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Karlsson, Elinor/0000-0002-4343-3776; Wade, Claire/0000-0003-3413-4771; Ponting, Chris/0000-0003-0202-7816; Heger, Andreas/0000-0001-7720-0447; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 119 TC 1221 Z9 1318 U1 46 U2 310 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 8 PY 2005 VL 438 IS 7069 BP 803 EP 819 DI 10.1038/nature04338 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990XX UT WOS:000233777800043 PM 16341006 ER PT J AU Zeng, X Tamai, K Doble, B Li, ST Huang, H Habas, R Okamura, H Woodgett, J He, X AF Zeng, X Tamai, K Doble, B Li, ST Huang, H Habas, R Okamura, H Woodgett, J He, X TI A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation SO NATURE LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; BETA-CATENIN; SUBSTRATE-SPECIFICITY; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; PATHWAY; AXIN; DROSOPHILA; MUTANTS; FAMILY AB Signalling by the Wnt family of secreted lipoproteins has essential functions in development and disease(1). The canonical Wnt/beta-catenin pathway requires a single-span transmembrane receptor, low-density lipoprotein (LDL)-receptor-related protein 6 (LRP6)(2-4), whose phosphorylation at multiple PPPSP motifs is induced upon stimulation by Wnt and is critical for signal transduction(5). The kinase responsible for LRP6 phosphorylation has not been identified. Here we provide biochemical and genetic evidence for a 'dual-kinase' mechanism for LRP6 phosphorylation and activation. Glycogen synthase kinase 3 (GSK3), which is known for its inhibitory role in Wnt signalling through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of LRP6. We show that Wnt induces sequential phosphorylation of LRP6 by GSK3 and casein kinase 1, and this dual phosphorylation promotes the engagement of LRP6 with the scaffolding protein Axin. We show further that a membrane-associated form of GSK3, in contrast with cytosolic GSK3, stimulates Wnt signalling and Xenopus axis duplication. Our results identify two key kinases mediating Wnt co-receptor activation, reveal an unexpected and intricate logic of Wnt/beta-catenin signalling, and illustrate GSK3 as a genuine switch that dictates both on and off states of a pivotal regulatory pathway. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol,Neurobiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. RP He, X (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol,Neurobiol Program, Boston, MA 02115 USA. EM xi.he@childrens.harvard.edu RI Woodgett, Jim/F-1087-2010; Doble, Bradley/L-7551-2016 OI Woodgett, Jim/0000-0003-3731-5797; Doble, Bradley/0000-0002-0260-2983 FU NIGMS NIH HHS [R01 GM074241, R01 GM074241-01] NR 30 TC 454 Z9 475 U1 9 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 8 PY 2005 VL 438 IS 7069 BP 873 EP 877 DI 10.1038/nature04185 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990XX UT WOS:000233777800055 PM 16341017 ER PT J AU Becker, MA Schumacher, HR Wortmann, RL MacDonald, PA Eustace, D Palo, WA Streit, J Joseph-Ridge, N AF Becker, MA Schumacher, HR Wortmann, RL MacDonald, PA Eustace, D Palo, WA Streit, J Joseph-Ridge, N TI Febuxostat compared with allopurinol in patients with hyperuricemia and gout SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID XANTHINE OXIDASE/XANTHINE DEHYDROGENASE; MONOSODIUM URATE; SERUM URATE; NON-PURINE; SELECTIVE INHIBITOR; ARTHRITIS; THERAPY; OXIDASE; CRYSTALLIZATION; SOLUBILITY AB BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. METHODS: We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area. RESULTS: The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). CONCLUSIONS: Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups. C1 Univ Chicago, Pritzker Sch Med, Med Ctr, Chicago, IL 60637 USA. Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Oklahoma, Dept Med, Tulsa, OK USA. TAP Pharmaceut Prod, Res & Dev, Lake Forest, IL USA. RP Becker, MA (reprint author), Univ Chicago, Pritzker Sch Med, Med Ctr, MC0930,5841 S Maryland Ave, Chicago, IL 60637 USA. EM mbecker@medicine.bsd.uchicago.edu NR 37 TC 473 Z9 514 U1 10 U2 54 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 DEC 8 PY 2005 VL 353 IS 23 BP 2450 EP 2461 DI 10.1056/NEJMoa050373 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 990OZ UT WOS:000233754400007 PM 16339094 ER PT J AU Rutgeerts, P Sandborn, WJ Feagan, BG Reinisch, W Olson, A Johanns, J Travers, S Rachmilewitz, D Hanauer, SB Lichtenstein, GR de Villiers, WJS Present, D Sands, BE Colombel, JF AF Rutgeerts, P Sandborn, WJ Feagan, BG Reinisch, W Olson, A Johanns, J Travers, S Rachmilewitz, D Hanauer, SB Lichtenstein, GR de Villiers, WJS Present, D Sands, BE Colombel, JF TI Infliximab for induction and maintenance therapy for ulcerative colitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; POUCH-ANAL ANASTOMOSIS; CROHNS-DISEASE; INTESTINAL INFLAMMATION; MEDICAL THERAPY; T-LYMPHOCYTES; CANCER-RISK; ANTIBODY; EXPRESSION AB BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor (alpha), is an established treatment for Crohn's disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -- the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -- evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P lessthan/equal 0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.). C1 Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Western Ontario, Robarts Res Inst, London, ON, Canada. Allgemeines Krankenhaus Wien, Univ Klin Innere Med 4, Vienna, Austria. Centocor Inc, Malvern, PA 19355 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. Univ Chicago, Chicago, IL 60637 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Kentucky, Lexington, KY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CHU Lille, Hop Huriez, Ctr Invest Clin, INSERM, F-59037 Lille, France. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Sandborn, WJ (reprint author), Univ Ziekenhuizen Leuven, UZ Gasthuisberg, Herestr 49, B-3000 Louvain, Belgium. EM sandborn.william@mayo.edu RI Feagan, Brian/M-4283-2015 NR 39 TC 1593 Z9 1661 U1 7 U2 74 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 DEC 8 PY 2005 VL 353 IS 23 BP 2462 EP 2476 DI 10.1056/NEJMoa050516 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 990OZ UT WOS:000233754400008 PM 16339095 ER PT J AU Cohen, HT McGovern, FJ AF Cohen, HT McGovern, FJ TI Renal-cell carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LINDAU TUMOR-SUPPRESSOR; HYPOXIA-INDUCIBLE FACTOR; TRANSFORMING-GROWTH-FACTOR; HOGG-DUBE-SYNDROME; PARENCHYMAL SPARING SURGERY; COLLECTING DUCT CARCINOMA; INTEGRATED STAGING SYSTEM; MONOCLONAL-ANTIBODY; RANDOMIZED-TRIAL; DENDRITIC CELLS C1 Boston Univ, Sch Med, Evans Biomed Res Ctr, Dept Med,Renal Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Hematol Oncol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Hematol Oncol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Renal Sect, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, HT (reprint author), Boston Univ, Sch Med, Evans Biomed Res Ctr, Dept Med,Renal Sect, 650 ALbany St,Rm X-535, Boston, MA 02118 USA. EM htcohen@bu.edu FU NCI NIH HHS [R01 CA079830, R01 CA79830]; NIDDK NIH HHS [R01 DK067569, R01 DK67569] NR 103 TC 779 Z9 823 U1 4 U2 42 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 DEC 8 PY 2005 VL 353 IS 23 BP 2477 EP 2490 DI 10.1056/NEJMra043172 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 990OZ UT WOS:000233754400009 PM 16339096 ER PT J AU Manini, A Marill, KA Ellinor, PT AF Manini, A Marill, KA Ellinor, PT TI Case 37-2005: A 35-year-old man with cardiac arrest while sleeping - The Brugada syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ST-SEGMENT ELEVATION; BUNDLE-BRANCH BLOCK; VENTRICULAR-FIBRILLATION; CARDIOPULMONARY-RESUSCITATION; ELECTROCARDIOGRAPHIC PATTERN; COMATOSE SURVIVORS; SODIUM-CHANNEL; HYPOTHERMIA; DEFIBRILLATION; INDIVIDUALS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Manini, A (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 34 TC 6 Z9 6 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 DEC 8 PY 2005 VL 353 IS 23 BP 2492 EP 2501 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 990OZ UT WOS:000233754400012 ER PT J AU Lin, NU Gelman, R Winer, EP AF Lin, NU Gelman, R Winer, EP TI Dose density in breast cancer: A simple message? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ADJUVANT THERAPY; CHEMOTHERAPY; EXPRESSION; PREDICTION; REGIMENS; TRIAL; WOMEN C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ewiner@partners.org NR 17 TC 3 Z9 4 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 DEC 7 PY 2005 VL 97 IS 23 BP 1712 EP 1714 DI 10.1093/jnci/dji438 PG 3 WC Oncology SC Oncology GA 993AL UT WOS:000233925000001 PM 16333021 ER PT J AU Serra-Pages, C Streuli, M Medley, QG AF Serra-Pages, C Streuli, M Medley, QG TI Liprin phosphorylation regulates binding to LAR: Evidence for liprin autophosphorylation SO BIOCHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; NUCLEOTIDE EXCHANGE FACTOR; ALPHA MOTIF SAM; INTERACTING PROTEINS; KINASE DOMAIN; FAMILY; TARGET; SMAUG; DICTYOSTELIUM; RECOGNITION AB The LAR transmembrane tyrosine phosphatase associates with liprin-alpha proteins and colocalizes with liprin-alpha 1 at focal adhesions. LAR has been implicated in axon guidance, and liprins are involved in synapse formation and synapse protein trafficking. Several liprin Mutants have weaker binding to LAR as assessed by yeast interaction trap assays, and the extents of in vitro and in vivo phosphorylation of these mutants were reduced relative to that of wild-type liprin-alpha 1. Treatment of liprin-alpha 1 with calf intestinal phosphatase weakened its interaction with the recombinant GST-LAR protein. A liprin LH region mutant that inhibited liprin phosphorylation did not bind to LAR as assessed by coprecipitation studies. Endogenous LAR was shown to bind phosphorylated liprin-alpha 1 from MDA-486 cells labeled in vivo with [P-32] orthophosphate. In further characterizing the phosphorylation of liprin, we found immunoprecipitates of liprin-alpha 1 expressed in COS-7 cells to incorporate phosphate after washes of up to 4 M NaCl. Additionally, purified liprin-alpha 1 derived from Sf-9 insect cells retained the ability to incorporate phosphate in in vitro phosphorylation assays, and a liprin-alpha 1 truncation Mutant incorporated phosphate after denaturation and/or renaturation in SDS gels. Finally, binding assays showed that liprin binds to ATP-agarose and that the interaction is challenged by free ATP, but not by free GTP. Moreover, liprin LH region mutations that inhibit liprin phosphorylation stabilized the association of liprin with ATP-agarose. Taken together, our results suggest that liprin autophosphorylation regulates its association with LAR. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Medley, QG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Quintus_Medley@dfci.harvard.edu FU NCI NIH HHS [R01 CA055547-09, R01 CA055547-10, R01 CA055547-08, CA75091, CA55547] NR 33 TC 16 Z9 16 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 6 PY 2005 VL 44 IS 48 BP 15715 EP 15724 DI 10.1021/bi051434f PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 989WO UT WOS:000233704900009 PM 16313174 ER PT J AU Ebert, AM Hume, GL Warren, KS Cook, NP Burns, CG Mohideen, MA Siegal, G Yelon, D Fishman, MC Garrity, DM AF Ebert, AM Hume, GL Warren, KS Cook, NP Burns, CG Mohideen, MA Siegal, G Yelon, D Fishman, MC Garrity, DM TI Calcium extrusion is critical for cardiac morphogenesis and rhythm in embryonic zebrafish hearts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heart development; arrhythmia; sodium calcium exchanger; Ca2+-ATPase ID NA+-CA2+ EXCHANGER; SARCOPLASMIC-RETICULUM; NA+/CA2+ EXCHANGER; CA2+-BINDING DOMAIN; CYCLOPIAZONIC ACID; EXPRESSION; NCX1; GENE; CA; MYOFIBRILLOGENESIS AB Calcium entry into myocytes drives contraction of the embryonic heart. To prepare for the next contraction, myocytes must extrude calcium from intracellular space via the Na+/Ca2+ exchanger (NCX1) or sequester it into the sarcoplasmic reticulum, via the sarcoplasmic reticulum Ca2+-ATPase2 (SERCA2). In mammals, defective calcium extrusion correlates with increased intracellular calcium levels and may be relevant to heart failure and sarcoplasmic dysfunction in adults. We report here that mutation of the cardiac-specific NCX1 (NCX1h) gene causes embryonic lethal cardiac arrhythmia in zebrafish tremblor (tre) embryos. The tre ventricle is nearly silent, whereas the atrium manifests a variety of arrhythmias including fibrillation. Calcium extrusion defects in tre mutants correlate with severe disruptions in sarcomere assembly, whereas mutations in the L-type calcium channel that abort calcium entry do not produce this phenotype. Knockdown of SERCA2 activity by morpholino-mediated translational inhibition or pharmacological inhibition causes embryonic lethality due to defects in cardiac contractility and morphology but, in contrast to tre mutation, does not produce arrhythmia. Analysis of intracellular calcium levels indicates that homozygous tre embryos develop calcium overload, which may contribute to the degeneration of cardiac function in this mutant. Thus, the inhibition of NCX1h versus SERCA2 activity differentially affects the pathophysiology of rhythm in the developing heart and suggests that relative levels of NCX1 and SERCA2 function are essential for normal development. C1 Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NYU, Sch Med, Skirball Inst Biomol Med, Dev Genet Program, New York, NY 10016 USA. RP Garrity, DM (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. EM deborah.garrity@colostate.edu FU NHLBI NIH HHS [HL49579, HL63206, R01 HL049579]; NIA NIH HHS [K01 AG023562]; NIDDK NIH HHS [DK55383] NR 36 TC 57 Z9 58 U1 0 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 DEC 6 PY 2005 VL 102 IS 49 BP 17705 EP 17710 DI 10.1073/pnas.0502683102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000031 PM 16314582 ER PT J AU Turley, SJ Lee, JW Dutton-Swain, N Mathis, D Benoist, C AF Turley, SJ Lee, JW Dutton-Swain, N Mathis, D Benoist, C TI Endocrine self and gut non-self intersect in the pancreatic lymph nodes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; diabetes; peritoneal lymphatics; enteropathy ID DEPENDENT DIABETES-MELLITUS; REACTIVE T-CELLS; CELIAC-DISEASE; BB RAT; MICE; AUTOANTIBODIES; PERMEABILITY; AUTOIMMUNITY; PATHOGENESIS; INITIATION AB The autoimmune cascade that culminates in diabetes initiates within pancreatic lymph nodes (PLNs). Here, we show that developmentally controlled lymphogenesis establishes a preferential trafficking route from the gut to the PLN, where T cells can be activated by antigens drained from the peritoneum and the gastrointestinal tract. Furthermore, intestinal stress modifies the presentation of pancreatic self-antigens in PLNs. The convergence of endocrine and intestinal contents within PLNs has significant implications for type 1 diabetes and may help to explain the link between autoimmune pathogenesis and environmental provocation. C1 Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK59658, P30 DK036836, R01 DK059658, P30 DK36836] NR 29 TC 79 Z9 80 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 DEC 6 PY 2005 VL 102 IS 49 BP 17729 EP 17733 DI 10.1073/pnas.0509006102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000035 PM 16317068 ER PT J AU Isakoff, MS Sansam, CG Tamayo, P Subramanian, A Evans, JA Fillmore, CM Wang, X Biegel, JA Pomeroy, SL Mesirov, JP Roberts, CWM AF Isakoff, MS Sansam, CG Tamayo, P Subramanian, A Evans, JA Fillmore, CM Wang, X Biegel, JA Pomeroy, SL Mesirov, JP Roberts, CWM TI Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin remodeling; gene expression analysis; mouse models; Swi/Snf ID GENE-EXPRESSION; RHABDOID TUMORS; CANCER; TUMORIGENESIS; HSNF5/INI1; MUTATIONS; CHROMATIN; COMPLEX; ARREST; INI1 AB Snf5 (Ini1/Baf47/Smarcb1), a core member of the Swi/Snf chromatin remodeling complex, is a potent tumor suppressor whose mechanism of action is largely unknown. Biallelic loss of Snf5 leads to the onset of aggressive cancers in both humans and mice. We have developed an innovative and widely applicable analytical technique for cross-species validation of cancer models and show that the gene expression profiles of our Snf5 murine models closely resemble those of human Snf5-deficient rhabdoid tumors. We exploit this system to produce what we believe to be the first report documenting the effects on gene expression of inactivating a Swi/Snf subunit in normal mammalian cells and to identify the transcriptional pathways regulated by Snf5. We demonstrate that the tumor suppressor activity of Snf5 depends on its regulation of cell cycle progression; Snf5 inactivation leads to aberrant upregulation of E2F targets and increased levels of p53 that are accompanied by apoptosis, polyploidy, and growth arrest. Further, conditional mouse models demonstrate that inactivation of p16Ink4a or Rb (retinoblastoma) does not accelerate tumor formation in Snf5 conditional mice, whereas mutation of p53 leads to a dramatic acceleration of tumor formation. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02141 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St M657, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU NCI NIH HHS [R01 CA046274, CA 46274] NR 32 TC 123 Z9 130 U1 2 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 DEC 6 PY 2005 VL 102 IS 49 BP 17745 EP 17750 DI 10.1073/pnas.0509014102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000038 PM 16301525 ER PT J AU Flaherty, AW AF Flaherty, AW TI Frontotemporal and dopaminergic control of idea generation and creative drive SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article; Proceedings Paper CT Neuroscience Conference on Anatomy of the Soul CY MAY 19-24, 2005 CL Ameland, NETHERLANDS DE frontal lobe; temporal lobe; hypergraphia; bipolar disorder; dopamine; motivation ID BIPOLAR AFFECTIVE-DISORDER; LATENT INHIBITION; BASAL GANGLIA; MANIA; ACHIEVEMENT; DEPRESSION; HYPERGRAPHIA; ASSOCIATION; DYSTONIA; PATTERNS AB This article presents a three-factor anatomical model of human idea generation and creative drive, focusing on interactions between the temporal lobes, frontal lobes, and limbic system. Evidence is drawn from functional imaging, drug studies, and lesion analysis. Temporal lobe changes, as in hypergraphia, often increase idea generation, sometimes at the expense of quality. Frontal lobe deficits may decrease idea generation, in part because of rigid judgments about an idea's worth. These phenomena are clearest in verbal creativity, and roughly parallel the pressured communication of temporal lobe epilepsy, mania, and Wernicke's aphasia- compared to the sparse speech and cognitive inflexibility of depression, Broca's aphasia, and other frontal lobe lesions. The phenomena also shape non-linguistic creativity, as in that of frontotemporal dementia. The appropriate balance between frontal and temporal activity is mediated by mutually inhibitory corticocortical interactions. Mesolimbic dopamine influences novelty seeking and creative drive. Dopamine agonists and antagonists have opposite effects on goal-directed behavior and hallucinations. Creative drive is not identical to skill-the latter depends more on neocortical association areas. However, drive correlates better with successful creative output than skill does. Traditional neuroscientific models of creativity, such as the left brain - right brain hemispheric model, emphasize skills primarily, and stress art and musical skill at the expense of language and mathematics. The three-factor model proposed here predicts findings in a broad range of normal and pathological states and can be tested in many experimental paradigms. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Flaherty, AW (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK905B,55 Fruit St, Boston, MA 02114 USA. EM aflaherty@partners.org FU NINDS NIH HHS [K08 NS002067-05, K08 NS02067-01] NR 55 TC 111 Z9 118 U1 6 U2 33 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 5 PY 2005 VL 493 IS 1 BP 147 EP 153 DI 10.1002/cne.20768 PG 7 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 984IL UT WOS:000233296400022 PM 16254989 ER PT J AU Heapy, A Otis, J Marcus, KS Frantsve, LM Janke, EA Shulman, M Bellmore, W Kerns, RD AF Heapy, A Otis, J Marcus, KS Frantsve, LM Janke, EA Shulman, M Bellmore, W Kerns, RD TI Intersession coping skill practice mediates the relationship between readiness for self-management treatment and goal accomplishment SO PAIN LA English DT Article DE chronic pain; adherence; PSOCQ; self-efficacy; self-management ID CHANGE QUESTIONNAIRE PSOCQ; CHRONIC PAIN; CHANGE MODEL; INVENTORY; STAGE; ADOPT AB Underlying pain self-management treatments is the expectation that patients must adhere to coping skill practice recommendations to obtain treatment benefits. Recently, a model of motivation for pain treatment has proposed that patients' readiness to adopt a self-management approach serves as a predictor of active participation in treatment, and ultimately, of improved outcomes. This study compared the ability of pain readiness to change, as measured by the Pain Stages of Change Questionnaire (PSOCQ), and self-efficacy (SE) ratings, to predict adherence and goal accomplishment in cognitive-behavioral therapy (CBT) for chronic pain. Further analyses tested the hypothesis that adherence mediated the relationship between readiness to change and goal accomplishment. Data were collected as part of a larger randomized controlled trial of primary care based CBT. Participants were 78 patients recruited from a VA primary care clinic. At pretreatment Ss completed the PSOCQ to assess readiness to adopt a self-management approach to chronic pain and an SE measure to quantify certainty of achieving up to five behavioral treatment goals. Criteria were means of aggregated intersession adherence ratings and mean post-treatment goal accomplishment ratings. Pre-treatment PSOCQ variables significantly predicted intersession adherence and goal accomplishment. SE did not significantly predict either criterion. The statistical relationship between pre-treatment PSOCQ and behavioral goal accomplishment was significantly attenuated when intersession adherence was taken into account. These data provide support for a motivational model of pain treatment that asserts adherence to therapist recommendations for coping skill practice mediates readiness to change and self-reported goal attainments. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 VA Connecticut Healthcare Syst, Psychol Serv 116B, West Haven, CT 06516 USA. Yale Univ, Sch Med, West Haven, CT 06516 USA. Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Cardinal Hlth, Philadelphia, PA USA. RP Heapy, A (reprint author), VA Connecticut Healthcare Syst, Psychol Serv 116B, 950 Campbell Ave, West Haven, CT 06516 USA. EM alicia.heapy@med.va.gov OI Otis, John/0000-0002-5441-7421 NR 17 TC 8 Z9 8 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2005 VL 118 IS 3 BP 360 EP 368 DI 10.1016/j.pain.2005.09.004 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 997WS UT WOS:000234280100009 PM 16289803 ER PT J AU Aktas, B Pozgajova, M Bergmeier, W Sunnarborg, S Offermanns, S Lee, D Wagner, DD Nieswandt, B AF Aktas, B Pozgajova, M Bergmeier, W Sunnarborg, S Offermanns, S Lee, D Wagner, DD Nieswandt, B TI Aspirin induces platelet receptor shedding via ADAM17 (TACE) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALPHA-CONVERTING ENZYME; GLYCOPROTEIN-VI; DOWN-REGULATION; L-SELECTIN; IN-VITRO; OXIDATIVE-PHOSPHORYLATION; ACETYLSALICYLIC-ACID; BLEEDING-TIME; METALLOPROTEINASE AB Aspirin is effective in the therapy of cardiovascular diseases, because it causes acetylation of cyclooxygenase 1 ( COX-1) leading to irreversible inhibition of platelets. Additional mechanisms can be suspected, because patients treated with other platelet COX inhibitors such as indomethacin do not display an increased bleeding tendency as observed for aspirin-treated patients. Recently, aspirin and other anti-inflammatory drugs were shown to induce shedding of L-selectin in neutrophils in a metalloproteinase-dependent manner. Therefore, we investigated the effects of aspirin on the von Willebrand Factor receptor complex glycoprotein ( GP) Ib-V-IX, whose lack or dysfunction causes bleeding in patients. As quantified by fluorescence-activated cell sorting analysis in whole blood, aspirin, but not its metabolite salicylic acid, induced dose-dependent shedding of human and murine GPIb alpha and GPV from the platelet surface, whereas other glycoproteins remained unaffected by this treatment. Biotinylated fragments of GPV were detected by immunoprecipitation in the supernatant of washed mouse platelets, and the expression level of GPIb alpha was decreased in these platelets as measured by Western blot analysis. Although shedding occurred normally in COX-1-deficient murine platelets, shedding was completely blocked by a broad-range metalloproteinase inhibitor and, more importantly, in mouse platelets expressing an inactive form of ADAM17. Shed fragments of GPIb alpha and GPV were elevated in the plasma of aspirin-injected mice compared with animals injected with control buffer. These data demonstrate that aspirin at high concentrations induces shedding of GPIb alpha and GPV by an ADAM17-dependent mechanism and that this process can occur in vivo. C1 Rudolf Virchow Ctr Expt Biomed, D-97078 Wurzburg, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany. RP Nieswandt, B (reprint author), Rudolf Virchow Ctr Expt Biomed, Verbacherstr 9, D-97078 Wurzburg, Germany. EM bernhard.nieswandt@virchow.uni-wuerzburg.de NR 43 TC 35 Z9 37 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 2005 VL 280 IS 48 BP 39716 EP 39722 DI 10.1074/jbc.M507762200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986PD UT WOS:000233461300008 PM 16179345 ER PT J AU Lim, GW Wang, SX Limb, JA Mao, JR AF Lim, GW Wang, SX Limb, JA Mao, JR TI Activity of adenylyl cyclase and protein kinase A contributes to morphine-induced spinal apoptosis SO NEUROSCIENCE LETTERS LA English DT Article DE apoptosis; opioid; adenylyl cyclase; protein kinase A ID ANTINOCICEPTIVE TOLERANCE; RECEPTOR ANTAGONIST; DOWN-REGULATION; NERVOUS-SYSTEM; DEPENDENCE; INHIBITION; NEURONS; CELLS; CAMP; RAT AB Our previous study has shown that chronic morphine exposure induces neuronal apoptosis within the spinal cord dorsal horn; however, the mechanisms of morphine-induced apoptosis remain unclear. Here we examined whether adenylyl cyclase (AC) and protein kinase A (PKA) would play a role in this process. Intrathecal morphine regimen (10 mu g, twice daily x 7 days) that resulted in antinociceptive tolerance induced spinal apoptosis as revealed by in situ terminal deoxynucleotidyl transferase (TdT)-UTP-biotin nick end labeling (TUNEL). The TUNEL-positive cells were detected primarily in the superficial laminae of the spinal cord dorsal horn, which was associated with an increase in the expression of activated caspase-3 and mitogen-activated protein kinase (MAPK) within the same spinal region. Co-administration of morphine with a broad AC inhibitor (ddA), a PKA inhibitor (1189), or a MAPK inhibitor (PD98059) substantially reduced the number of TUNEL-positive cells, as compared with the morphine alone group. The results indicate that the spinal AC and PKA pathway through intracellular MAPK may be contributory to the cellular mechanisms of morphine-induced apoptosis. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Pain Med,Pain Res, Boston, MA 02114 USA. Konkuk Univ, Dept Anesthesia & Pain Med, Seoul, South Korea. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Pain Med,Pain Res, Suite WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [NS42661, NS45681] NR 28 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 2 PY 2005 VL 389 IS 2 BP 104 EP 108 DI 10.1016/j.neulet.2005.07.035 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 968UH UT WOS:000232187500009 PM 16102899 ER PT J AU Cydulka, RK Rowe, BH Clark, S Emerman, CL Rimm, AR Camargo, CA AF Cydulka, RK Rowe, BH Clark, S Emerman, CL Rimm, AR Camargo, CA TI Gender differences in emergency department patients with chronic obstructive pulmonary disease, exacerbation SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; exacerbation; gender; emergency ID QUALITY-OF-LIFE; ACUTE ASTHMA; SEX-DIFFERENCES; COPD; ADULTS; WOMEN; HOSPITALIZATION; QUESTIONNAIRE; MULTICENTER; POPULATION AB Objectives: Although more men are diagnosed as having chronic obstructive pulmonary disease (COPD), its prevalence is increasing among women. Little is known about gender differences in exacerbations of COPD. The objective of this study was to determine if acute presentation, management, and outcomes differ among men and women seeking care in the emergency department (ED) for exacerbation of COPD. Methods: This was a secondary analysis of a prospective cohort study of ED patients aged 55 years or older who presented with an exacerbation of COPD. Subjects underwent structured interviews in the ED and two weeks later. Results: The cohort consisted of 397 subjects with COPD, of whom 52% were women. Self-report of COPD only tended to be more common among men (61% of men vs. 52% of women), while mixed COPD/asthma tended to be more common among women (39% vs. 48%; p = 0.10). Despite reporting similar chronic symptom severity, women were less likely than men to use anticholinergic agents before their ED visit (59% vs. 69%; p = 0.04). During the exacerbation, women initiated less home therapy and were less likely to seek emergency care within the first 24 hours of symptom onset (25% vs. 36%; p = 0.01). Although ED care and disposition were similar, post-ED outcomes differed. At two-week follow-up, men were more likely to report an ongoing exacerbation (42% vs. 31%; p = 0.03). Conclusions: Men and women who present to the ED for treatment of an exacerbation of COPD have substantial differences in long-term medication use, self-treatment during exacerbation, delay in emergency care, and post-ED outcomes. Further studies are warranted to confirm and explain these gender-related differences. C1 Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44109 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Epidemiol & Biostat, Cleveland, OH 44109 USA. Univ Alberta, Div Emergency Med, Edmonton, AB, Canada. Capital Hlth, Edmonton, AB, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Cydulka, RK (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, 2500 MetroHlth Dr,Room S1-203, Cleveland, OH 44109 USA. EM rcydulka@metrohealth.org FU NHLBI NIH HHS [R01 HL63841]; NIEHS NIH HHS [T32 ES07069] NR 37 TC 18 Z9 18 U1 2 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2005 VL 12 IS 12 BP 1173 EP 1179 DI 10.1197/j.aem.2005.2005.06.025 PG 7 WC Emergency Medicine SC Emergency Medicine GA 990QW UT WOS:000233759300006 PM 16282511 ER PT J AU Dobscha, SK Snyder, KM Corson, K Ganzini, L AF Dobscha, SK Snyder, KM Corson, K Ganzini, L TI Psychiatry resident graduate comfort with general medical issues: Impact of an integrated psychiatry-primary medical care training track SO ACADEMIC PSYCHIATRY LA English DT Article ID MORTALITY AB Objective: To determine if a psychiatry-primary medical care ( PPMC) training track impacts comfort and behaviors related to addressing general medical issues after residency. Method: Thirty five psychiatry resident graduates completed mailed surveys; nine of them had completed the PPMC track. Results: Compared to non-PPMC participants, PPMC participants felt better prepared to address medical issues and tended to perform more consultations and feel more comfortable referring patients to general medical providers. They were not more likely to perform routine health screenings. Conclusion: Integrated training tracks may impact resident preparedness and career choice but may be insufficient to influence practice behaviors related to delivering general medical care. C1 Portland VA Med Ctr, Behavior Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland, OR USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Behavior Hlth & Clin Neurosci Div, POB 1034 P3MHDC, Portland, OR 97207 USA. EM steven.dobscha@med.va.gov NR 9 TC 7 Z9 7 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD DEC PY 2005 VL 29 IS 5 BP 448 EP 451 DI 10.1176/appi.ap.29.5.448 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 998EK UT WOS:000234301200008 PM 16387968 ER PT J AU Deisboeck, TS Demuth, T Mansury, Y AF Deisboeck, TS Demuth, T Mansury, Y TI Correlating velocity patterns with spatial dynamics in glioma cell migration SO ACTA BIOTHEORETICA LA English DT Article DE glioma cell migration; detrended fluctuations analysis ID EPIDERMAL-GROWTH-FACTOR; IN-VITRO; FACTOR-RECEPTOR; DNA-SEQUENCES; EXPRESSION; GRADE AB Highly malignant neuroepithelial tumors are known for their extensive tissue invasion. Investigating the relationship between their spatial behavior and temporal patterns by employing detrended fluctuation analysis (DFA), we report here that faster glioma cell motility is accompanied by both greater predictability of the cells' migration velocity and concomitantly, more directionality in the cells' migration paths. Implications of this finding for both experimental and clinical cancer research are discussed. C1 MIT, Complex Biosyst Modeling Lab, HST Biomed Engn Ctr, Cambridge, MA 02139 USA. Harvard Univ, MIT, Massachusetts Gen Hosp, HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA. RP Deisboeck, TS (reprint author), MIT, Complex Biosyst Modeling Lab, HST Biomed Engn Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA 09502, CA 085139] NR 14 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0001-5342 J9 ACTA BIOTHEOR JI Acta Biotheor. PD DEC PY 2005 VL 53 IS 3 BP 181 EP 190 DI 10.1007/s10441-005-2527-1 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 990MN UT WOS:000233747600003 PM 16329007 ER PT J AU Gilmer, WS Trivedi, MH Rush, AJ Wisniewski, SR Luther, J Howland, RH Yohanna, D Khan, A Alpert, J AF Gilmer, WS Trivedi, MH Rush, AJ Wisniewski, SR Luther, J Howland, RH Yohanna, D Khan, A Alpert, J TI Factors associated with chronic depressive episodes: a preliminary report from the STAR-D project SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE depression; episode; duration; chronic; socioeconomic ID PROSPECTIVE FOLLOW-UP; UNIPOLAR AFFECTIVE-DISORDER; PRIMARY MAJOR DEPRESSIONS; MENTAL-HEALTH SURVEY; REPORT QIDS-SR; RISK-FACTORS; PSYCHOMETRIC EVALUATION; GENERAL-POPULATION; SYMPTOMATOLOGY IDS; QUICK INVENTORY AB Objective: To identify baseline sociodemographic and clinical factors associated with a current chronic major depressive episode (MDE). Method: Outpatients with major depressive disorder enrolled in 41 US primary or psychiatric care sites were divided into two groups based on self-report of current episode length (< 24 or >= 24 months). Logistic regression models were used to identify factors associated with chronicity of current depressive episode. Results: About 21.2% of 1380 subjects were in current, chronic MDEs. Older age, less education, lower income, no private insurance, unemployment, greater general medical illness burden, lower physical quality of life, concurrent generalized anxiety disorder, fewer prior episodes, and history of prior suicide attempts were all associated with chronic episodes. Blacks, Hispanics, and patients receiving care in primary as opposed to psychiatric care settings exhibited greater chronicity. Conclusions: Chronic depressive episodes are common and are associated with greater illness burden, comorbidity, socioeconomic disadvantage, and racial/ethnic minority status. C1 Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. Univ Kansas, Sch Med, Dept Psychiat & Behav Sci, Wichita, KS 67214 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gilmer, WS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, 446 E Ontario St 7-100, Chicago, IL 60611 USA. EM w-gilmer@northwestern.edu RI 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 [N01MH90003] NR 68 TC 95 Z9 96 U1 4 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 2005 VL 112 IS 6 BP 425 EP 433 DI 10.1111/j.1600-0447.2005.00633.x PG 9 WC Psychiatry SC Psychiatry GA 982DN UT WOS:000233138200004 PM 16279871 ER PT J AU Shlipak, M AF Shlipak, M TI Diabetic nephropathy SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID RENAL-DISEASE; MELLITUS; PROGRESSION; PROTEINURIA; MORTALITY C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Shlipak, M (reprint author), San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD DEC 1 PY 2005 VL 72 IS 11 BP 2299 EP 2302 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 990ZC UT WOS:000233780900016 ER PT J AU Bozkurt, B Deswal, A AF Bozkurt, B Deswal, A TI Obesity as a prognostic factor in chronic symptomatic heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR MASS; MORBID-OBESITY; WEIGHT-LOSS; RISK FACTOR; FOLLOW-UP; DISEASE AB Background Obesity is considered as an independent risk factor for development of heart failure (HF); however, its role in the progression of HF independent of atherosclerotic heart disease, hypertension, and diabetes is not well described. Methods To identify the role of obesity in HF outcomes, we analyzed the Digitalis Investigation, Group database with 7788 patients with chronic stable HF. Subjects with body mass index of >= 18.5 and <25 kg/m(2) were categorized as normal weight, >= 25.0 and <30 kg/m2 as overweight, and >= 30.0 kg/m2 as obese. Results Compared with normal weight,, overweight or obese patients had lower all-cause mortality (37.8%, 32.4%, and 28.5%, P < .0001) and lower HF mortality (38.7%, 31.2%, and 33.6%, P = .01). After adjustment for differences in baseline characteristics, the overweight (HR 0.87, 95% CI 0.79-0.95, P = .002) and the obese (HR 0.82, 95% CI 0.73-0.92, P = .0005) had better survival rates compared with normal-weight groups. Similarly, the overweight (HR 0.76, 95% CI 0.65-0.88, P = .0003) or the obese (HR 0.79, 95% CI 0.63-0.88, P = .005) patients had better HF survival rates. After adjustment for baseline differences, the rate of hospitalizations was similar in the 3 groups. Conclusions in patients with chronic symptomatic HF, obesity or overweight status was associated with a lower risk for mortality but a similar risk for hospitalization compared with normal weight status. Prospective studies evaluating the risks and benefits of sustenance of obesity or weight loss are needed in this population. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Bozkurt, B (reprint author), Vet Affairs Med Ctr, 111 MCL 4C-211,2002 Holcombe Blvd, Houston, TX 77030 USA. EM bbozkurt@bcm.tmc.edu NR 16 TC 45 Z9 45 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2005 VL 150 IS 6 BP 1233 EP 1238 DI 10.1016/j.ahj.2005.02.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000TJ UT WOS:000234485000020 PM 16338264 ER PT J AU Pinto, DS Kirtane, AJ Ruocco, NA Deibele, AJ Shui, A Buros, J Murphy, SA Gibson, CM AF Pinto, DS Kirtane, AJ Ruocco, NA Deibele, AJ Shui, A Buros, J Murphy, SA Gibson, CM TI Administration of intracoronary Eptifibatide during ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY INTERVENTION; UNSTABLE ANGINA; ABCIXIMAB; ANGIOPLASTY; PERFUSION; THROMBUS; DISSOLUTION; INHIBITION; TIROFIBAN; GRADE AB Distal embolization of atherothrombotic material during primary percutaneous coronary intervention (PCI) is associated with impaired myocardial perfusion, abnormal left ventricular function, and higher mortality. At high local concentrations, glycoprotein IIb/IIIa receptor antagonists have been demonstrated to promote clot disaggregation in vitro. Intracoronary administration of eptifibatide in vivo may increase local drug concentration by several orders of magnitude and promote clot disaggregation with a minimal increase in systemic drug concentrations. We hypothesized that intracoronary administration of eptifibatide before primary PCI for ST-elevation myocardial infarction would be safe and would be associated with high rates of normal myocardial perfusion. Clinical and angiographic data were pooled from patients who underwent primary PCI and received intracoronary eptifibatide as part of clinical practice. In-hospital adverse events were collected retrospectively. No deaths, urgent revascularizations, or reinfarctions were observed among the 59 patients who were treated with intracoronary eptifibatide. There were no Thrombolysis In Myocardial Infarction (TIMI) major bleeding events. Two TIMI minor bleeding events were noted. Normal TIMI myocardial perfusion grade 3 flow after PCI was noted in 54.4% of patients. No adverse events. including arrhythmias, were noted during intracoronary eptifibatide administration. In conclusion, intracoronary eptifibatide can be administered safely during primary PCI and is associated with few adverse events. Relatively high rates of normal myocardial perfusion were observed after primary PCI with adjunctive intracoronary eptifibatide. Further prospective randomized trials are warranted to evaluate the efficacy and safety of intracoronary eptifibatide. (c) 2005 Elsevier Inc. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Caritas Norwood Hosp, Div Cardiol, Norwood, MA USA. PERFUSE Angiog Core Lab, Boston, MA USA. TIMI Study Grp, Boston, MA USA. Duluth Clin, Div Cardiol, Duluth, MN USA. RP Gibson, CM (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. EM mgibson@perfuse.org NR 17 TC 13 Z9 14 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2005 VL 96 IS 11 BP 1494 EP 1497 DI 10.1016/j.amjcard.2005.07.056 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 994HM UT WOS:000234021900005 PM 16310428 ER PT J AU Hugli, O Braun, JE Kim, S Pelletier, AJ Camargo, CA AF Hugli, O Braun, JE Kim, S Pelletier, AJ Camargo, CA TI United States emergency department visits for acute decompensated heart failure, 1992 to 2001 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; ISOSORBIDE DINITRATE; THERAPY; TRENDS; ASSOCIATION; DISPARITIES; DYSFUNCTION; GUIDELINES; FUROSEMIDE; INSURANCE AB Heart failure is a significant public health problem. The epidemiology and practice pattern of emergency department (ED) visits for acute decompensated heart failure (ADHF) have not been well characterized. A better description is essential to highlight areas in which improvements or additional research are needed. We analyzed all ED visits for ADHF of patients >= 40 years old using the data of the National Hospital Ambulatory Medical Care Survey from, 1992 to 2001. During this 10-year period, an estimated 10.5 million ED visits occurred for ADHF, representing 2.9% of all ED visits. The number of ADHF visits increased on average by 18,500 per year, for a 19.4% absolute increase during the decade. The rate per 1,000 United States population was unchanged. The average patient was 74 years old, and patients >= 65 years accounted for 79% of visits. Loop diuretics were administered in 63% and vasodilators in 29% of visits. The ED visit rate per 1,000 United States population was 53% higher in blacks than in whites (14.2 vs 9.3). In a multivariate model, white race was a significant predictor of hospitalization. In conclusion, during the past decade, the absolute number of ED visits for ADHF has increased owing to the aging population. Diuretics remain the most common treatment. Race-related differences in hospitalization merit additional study. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Hugli, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. EM ohugli@partners.org OI Hugli, Olivier/0000-0003-2312-1625 NR 28 TC 38 Z9 39 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2005 VL 96 IS 11 BP 1537 EP 1542 DI 10.1016/j.amjcard.2005.07.064 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 994HM UT WOS:000234021900013 PM 16310436 ER PT J AU Rahemtullah, A Szyfelbein, K Zembowiez, A AF Rahemtullah, A Szyfelbein, K Zembowiez, A TI Glomus coccygeum - Report of a case and review of the literature SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Review DE glomus coccygeum; pilonidal cyst; coccygeal region; glomus tumor ID TUMOR AB The glomus coccygeum is a vestigial structure related to the canals of Sucquet-Hoyer, an arteriovenous anastomosis surrounded by glomus cells derived from modified smooth muscle and involved in thermoregulation. It is an incidental finding in specimens from the sacral area and may represent a diagnostic challenge to the unaware observer. We present a case of a glomus coccygeum, presenting as a 1.5-mm structure adjacent to a typical pilonidal cyst excised from a 7-month-old boy, which was the subject of a second opinion consultation. The lesion showed small to medium sized clusters of predominantly epithelioid cells with moderate amounts of clear to eosinophilic cytoplasm, intercellular borders, and plump, round nuclei with fine chromatin. These cells were closely associated with small vascular channels and nerves. Immunohistochemistry revealed that the epithelioid cells expressed vimentin, muscle-specific actin, neuron-specific enolase, and S-100 protein, were weakly positive for smooth muscle actin, and negative for desmin, synaptophysin, and chromogranin. The endothelial cells of the vascular channels were antibody CD31 positive. Recognition of the histologic features of glomus coccygeum is important to avoid confusion with glomus tumor and neural or smooth muscle neoplasms in the sacral area. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zembowiez, A (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, 820 Warren Bldg,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 12 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD DEC PY 2005 VL 27 IS 6 BP 497 EP 499 DI 10.1097/01.dad.0000149079.70872.a7 PG 3 WC Dermatology SC Dermatology GA 989WS UT WOS:000233705300005 PM 16314705 ER PT J AU Ahmad, NA Kochman, ML Ginsberg, GG AF Ahmad, NA Kochman, ML Ginsberg, GG TI Practice patterns and attitudes toward the role of endoscopic ultrasound in staging of gastrointestinal malignancies: A survey of physicians and surgeons SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/105th Annual Meeting of the American-Gastroenterological-Association CY MAY 16-20, 2004 CL New Orleans, LA SP Amer Gastroenterol Assoc ID ESOPHAGEAL-CARCINOMA; ULTRASONOGRAPHY; CANCER; EUS; CT AB BACKGROUND AND AIMS: It is unknown how physician specialties other than gastroenterologists that manage gastrointestinal (GI) malignancies utilize endoscopic ultrasound (EUS) in their practices. The aim of this study was to (i) assess the proportion of gastroenterologists, oncologists, and surgeons that utilize EUS for staging of GI malignancies; (ii) assess the general availability of EUS; and (iii) determine which factors are associated with the use and availability of EUS. METHODS: A self-administered questionnaire was mailed out to 1,200 randomly selected gastroenterologists, oncologists, and surgeons throughout the United States. RESULTS: The data was analyzed from 521 (43%) responses. There were 60% respondents who had EUS available within their practices. There was greater availability of EUS within the practices of surgeons (81%; p < 0.001), within academic practices (87%; p= < 0.001), and in practices that serve a population > 500,000 (p < 0.001). The majority of respondents (71%) utilized EUS in their practices. There was a similar utilization of EUS across specialties (p= NS). There was greater utilization of EUS in academic centers (82%; p < 0.001), in practices that served a community of > 500,000 (p= 0.003), and among respondents who had been in practice for less than 5 yr (p= 0.005). Employing logistic regression models for utilization of EUS, lesser number of years in practice, and availability of EUS were found to be the only significant predictors of utilization. CONCLUSIONS: The majority of practitioners utilized EUS in management of GI malignancies. There was similar utilization of EUS across specialties. EUS is available to the majority of practitioners who manage GI malignancies. C1 Hosp Univ Penn, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Dept Med, Div Gastroenterol, Philadelphia, PA USA. RP Ahmad, NA (reprint author), Hosp Univ Penn, Div Gastroenterol, Dept Med, 3rd Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. NR 11 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2005 VL 100 IS 12 BP 2662 EP 2668 DI 10.1111/j.1572-0241.2005.00281.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 988UV UT WOS:000233627400011 PM 16393217 ER PT J AU Lieberman, D AF Lieberman, D TI Race, gender, and colorectal cancer screening SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID AVERAGE-RISK; GUIDELINES; ADULTS; WOMEN AB Colorectal cancer (CRC) screening in asymptomatic, average-risk populations can reduce mortality and incidence of CRC. The United States Preventive Services Task Force, the American Cancer Society, and the Multi-Society Task Force all recommend initiation of screening at the age of 50 yr for men and women of all races, with an identical menu of screening options. However, there are important differences in risk based on gender, race, and ethnicity. These differences could influence the timing of initiation of screening, and the most optimal form of screening test. This commentary discusses the basis for these differences, and proposes that we should consider customization of screening based on gender, race, and ethnicity. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97201 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol, P3-GI 1037 SW Vet Hosp Rd, Portland, OR 97201 USA. NR 10 TC 33 Z9 33 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2005 VL 100 IS 12 BP 2756 EP 2758 DI 10.1111/j.1572-0241.2005.00352.x PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 988UV UT WOS:000233627400025 PM 16393231 ER PT J AU Schreiber, ZA Brau, N AF Schreiber, ZA Brau, N TI Acquired factor VIII inhibitor in patients with hepatitis C virus infection and the role of interferon-alpha: A case report SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE acquired factor VIII inhibitor; hepatitis C; interferon-alpha; human immunodeficiency virus ID CHRONIC MYELOGENOUS LEUKEMIA; THERAPY; ANTIBODIES; DISEASE AB A patient with HIV and hepatitis C virus (HCV) co-infection developed an autoantibody to factor VIII after 8.7 months of treatment with pegylated interferon-a and ribavirin. Three previous cases of the development of factor VIII autoantibody in patients infected with the hepatitis C virus have been reported. Only one of these patients was treated with interferon-alpha, and this patient had hemophilia A, a condition prone to development of factor VIII autoantibody, even without interferon treatment. It is possible that chronic HCV infection itself, which has been associated with immunological disorders, is responsible for this phenomenon, but the immunomodulatory properties of interferon-alpha may also contribute to this rare occurrence. No previous case of factor VIII inhibitor in a patient infected with HIV has been reported. C1 Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Bronx Vet Adm Med Ctr, Viral Hepatitis Program, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Schreiber, ZA (reprint author), Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. NR 17 TC 11 Z9 12 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 DEC PY 2005 VL 80 IS 4 BP 295 EP 298 DI 10.1002/ajh.20405 PG 4 WC Hematology SC Hematology GA 989TM UT WOS:000233696800008 PM 16315253 ER PT J AU Plenge, RM Padyukov, L Remmers, EF Purcell, S Lee, AT Karlson, EW Wolfe, F Kastner, DL Alfredsson, L Altshuler, D Gregersen, PK Klareskog, L Rioux, JD AF Plenge, RM Padyukov, L Remmers, EF Purcell, S Lee, AT Karlson, EW Wolfe, F Kastner, DL Alfredsson, L Altshuler, D Gregersen, PK Klareskog, L Rioux, JD TI Replication of putative candidate-gene associations with rheumatoid arthritis in > 4,000 samples from North America and Sweden: Association of susceptibility with PTPN22, CTLA4, and PADI4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; JUVENILE IDIOPATHIC ARTHRITIS; CYCLIC CITRULLINATED PEPTIDE; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; FACTOR RECEPTOR-II; CROHNS-DISEASE; AUTOIMMUNE-DISEASES; SHARED EPITOPE; FUNCTIONAL VARIANT AB Candidate-gene association studies in rheumatoid arthritis (RA) have lead to encouraging yet apparently inconsistent results. One explanation for the inconsistency is insufficient power to detect modest effects in the context of a low prior probability of a true effect. To overcome this limitation, we selected alleles with an increased probability of a disease association, on the basis of a review of the literature on RA and other autoimmune diseases, and tested them for association with RA susceptibility in a sample collection powered to detect modest genetic effects. We tested 17 alleles from 14 genes in 2,370 RA cases and 1,757 controls from the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) collections. We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody positive RA (odds ratio [OR] 1.49; P = .001), using previously untested EIRA samples. We provide support for an association of CTLA4 (CT60 allele, OR 1.23; P = .001) and PADI4 (PADI4_94, OR 1.24; P = .001) with the development of RA, but only in the NARAC cohort. The CTLA4 association is stronger in patients with RA from both cohorts who are seropositive for anti-citrulline antibodies (P = .006). Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P = .004) and that PTPN22 has a stronger effect in males than in females (P = .03). A meta-analysis failed to demonstrate an association of the remaining alleles with RA susceptibility, suggesting that the previously published associations may represent false-positive results. Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA. C1 Univ Montreal, Broad Inst MIT & Harvard, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada. Program Med & Populat Genet, Cambridge, MA USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Karolinska Inst, Rheumatol Unit, Stockholm, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. N Shore LIJ Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA. Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Rioux, JD (reprint author), Univ Montreal, Broad Inst MIT & Harvard, 5000 Belanger, Montreal, PQ H1T 1C8, Canada. EM rioux@broad.mit.edu RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; Rioux, John/A-9599-2015; OI Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; Rioux, John/0000-0001-7560-8326; Klareskog, Lars/0000-0001-9601-6186; Alfredsson, Lars/0000-0003-1688-6697 FU Intramural NIH HHS; NIAID NIH HHS [K08 AI 55314, K08 AI055314]; NIAMS NIH HHS [K24 AR0524-01, N01-AR-2-2263, P60 AR047782, P60 AR47782-05, R01 AR049880, R01 AR49880-01, R01-AR44222] NR 92 TC 334 Z9 349 U1 6 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2005 VL 77 IS 6 BP 1044 EP 1060 DI 10.1086/498651 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 983OE UT WOS:000233241200013 PM 16380915 ER PT J AU Pogach, L Xie, MG Yue, ST Tseng, CL Maney, M Rajan, M Tiwari, A Kolassa, J Helmer, D Crystal, S Safford, M AF Pogach, L Xie, MG Yue, ST Tseng, CL Maney, M Rajan, M Tiwari, A Kolassa, J Helmer, D Crystal, S Safford, M TI Diabetes healthcare quality report cards: How accurate are the grades? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OF-CARE; PERFORMANCE-MEASUREMENT; SYSTEM; RISK; TRANSFORMATION; INFORMATION; MANAGEMENT; FACILITIES; MORTALITY; PROVIDERS AB Objective: To evaluate the accuracy and precision of random sampling in identifying healthcare system outliers in diabetes performance measures. Study Design: Cross-sectional analysis of 79 Veterans Health Administration facilities serving 250317 patients with diabetes mellitus between October 1, 1999, and September 30, 2000. Methods: Primary outcome measures were poor glycosylated hemoglobin (A1C) control and good low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) control. Facility performance for each measure was calculated using 150 separate random samples and was compared with results using the bootstrap method as the criterion standard for determining outlier status (defined as a >= 5% difference from the mean, within the 10th or 90th percentile, or >= 2 SlDs from the mean). Results: The study population was largely male (97.4%), with 54.0% of subjects being 65 years or older. The facility-level mean performances were 22.8% for poor A1C control, 53.1 % for good LDL-C control, and 55.3% for good BP control. Comparing the random sampling method with the bootstrap method, the sensitivity ranged between 0.64 and 0.83 for the 3 outcome measures, positive predictive values ranged between 0.55 and 0.88, and specificity and negative predictive values ranged between 0.88 and 0.99. Conclusions: The specificity and negative predictive value of the random sampling method in identifying nonoutliers in performance were generally high, while its sensitivity and positive predictive value were moderate. The use of random sampling to determine performance for individual outcome measures may be most appropriate for internal quality improvement rather than for public reporting. C1 VA New Jersey Hlth Care Syst, Ctr Healthcare Knowledge Management, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Birmingham VA Med Ctr, Deep S Ctr Effectivenss, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. RP Pogach, L (reprint author), VA New Jersey Hlth Care Syst, Ctr Healthcare Knowledge Management, 385 Tremont Ave,111 Med, E Orange, NJ 07018 USA. EM leonaid.pogach@med.va.gov NR 36 TC 1 Z9 1 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2005 VL 11 IS 12 BP 797 EP 804 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 994GD UT WOS:000234018300006 PM 16336064 ER PT J AU McNaughton-Collins, M Barry, MJ AF McNaughton-Collins, M Barry, MJ TI Managing patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE benign prostatic hyperplasia; diagnosis; treatment ID DIGITAL RECTAL EXAMINATION; COMMUNITY-BASED POPULATION; NATURAL-HISTORY; RISK-FACTORS; TRANSURETHRAL RESECTION; EVALUATING MEN; CLINICAL-TRIAL; PRESSURE-FLOW; FINASTERIDE; RETENTION AB Many men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia can be managed safely and effectively by primary care providers. After a basic evaluation to exclude other diseases that may cause lower urinary tract symptoms, quantifying the degree of symptoms and bother,and perhaps making an assessment of prostate size, the primary care provider can determine which men require immediate evaluation by a urologist and which men may choose among various treatment options, including watchful waiting and various single agent or combination medication strategies. Recent information about risk factors for disease progression has also helped to inform patient decisions on which treatment option is best for the individual patient. The purpose of this review is to provide primary care providers with an approach to the management of men with lower Urinary tract symptoms suggestive of benign prostatic hyperplasia. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org NR 59 TC 11 Z9 13 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1331 EP 1339 DI 10.1016/j.amjmed.2004.12.033 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700005 PM 16378773 ER PT J AU Cohen, LS Soares, CN Joffe, H AF Cohen, LS Soares, CN Joffe, H TI Diagnosis and management of mood disorders during the menopausal transition SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Perinatl & Reprod Psychiat, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1408 EP 1408 DI 10.1016/j.amjmed.2005.10.018 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700031 ER PT J AU Grady, D Sawaya, GF AF Grady, D Sawaya, GF TI Discontinuation of postmenopausal hormone therapy SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1411 EP 1411 DI 10.1016/j.amjmed.2005.10.028 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700041 ER PT J AU Sherman, S Nerurkar, L Miller, H Schiff, I AF Sherman, S Nerurkar, L Miller, H Schiff, I TI Research opportunities for reducing the burden of menopause-related symptoms SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 NIA, NIH, Bethesda, MD 20892 USA. NIH, Off Med Applicat Res, Off Director, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1411 EP 1412 DI 10.1016/j.amjmed.2005.10.029 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700042 ER PT J AU Feldman, AM Benz, EJ AF Feldman, AM Benz, EJ TI Restructuring the academic department of internal medicine SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID HEALTH CENTERS; RAPID CHANGES; EDUCATION; FUTURE; CARE C1 Thomas Jefferson Univ, Coll Med, Dept Med, Philadelphia, PA 19107 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Feldman, AM (reprint author), Jefferson Med Coll, Dept Med, 1025 Walnut St,Suite 822, Philadelphia, PA 19107 USA. EM arthur.feldman@jefferson.edu NR 35 TC 0 Z9 0 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1430 EP 1435 DI 10.1016/j.amjmed.2005.10.002 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700046 PM 16378806 ER PT J AU Smirnakis, KV Plati, A Wolf, M Thadhani, R Ecker, J AF Smirnakis, KV Plati, A Wolf, M Thadhani, R Ecker, J TI Predicting gestational diabetes: Which is the best early serum marker? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 290 BP S90 EP S90 DI 10.1016/j.ajog.2005.10.302 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800289 ER PT J AU Chen, YL Xu, SW van Beek, J Kennedy, L McLeod, M Renzoni, EA Bou-Gharios, G Wilcox-Adelman, S Goetinck, PF Eastwood, M Black, CM Abraham, DJ Leask, A AF Chen, YL Xu, SW van Beek, J Kennedy, L McLeod, M Renzoni, EA Bou-Gharios, G Wilcox-Adelman, S Goetinck, PF Eastwood, M Black, CM Abraham, DJ Leask, A TI Matrix contraction by dermal fibroblasts requires transforming growth factor-beta/activin-linked kinase 5, heparan sulfate-containing proteoglycans, and MEK/ERK - Insights into pathological scarring in chronic fibrotic disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SCLERODERMA SKIN FIBROBLASTS; FACTOR-BETA; CYTOSKELETAL ORGANIZATION; WOUND REPAIR; EXPRESSION; FIBROSIS; COLLAGEN; SYNDECAN-4; GENE; INHIBITION AB Scarring is characterized by excessive synthesis and contraction of extracellular matrix. Here, we show that fibroblasts from scarred (lesional) areas of patients with the chronic fibrotic disorder diffuse scleroderma [diffuse systemic sclerosis (dSSc)] show an enhanced ability to adhere to and contract extracellular matrix, relative to fibroblasts from unscarred (nonlesional) areas of dSSc patients and dermal fibroblasts from normal, healthy individuals. The contractile abilities of normal and dSSc dermal fibroblasts were suppressed by blocking heparin sulfate-containing proteoglycan biosynthesis or antagonizing transforming growth factor-P receptor type I [activin-linked kinase (ALK5)] or ras/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Compared with both normal and nonlesional fibroblasts, lesional dSSc fibroblasts overexpressed the heparin sulfate-containing proteoglycan syndecan 4. We also found that the procontractile signals from transforming growth factor (TGF)-beta were integrated through syndecan 4 and MEK/ERK because the ability of TGF beta to induce contraction of dermal fibroblasts was prevented by MEK antagonism. TGF beta could not induce a contractile phenotype or phosphorylate ERK in syndecan 4(-/-) dermal fibroblasts. These results suggest that integrating TGF beta and ERK signals via syndecan 4 is essential for the contractile ability of dermal fibroblasts. We conclude that antagonizing MEK/ERK, TGF beta 1/ALK5, or syndecan 4 may alleviate scarring in chronic fibrotic disease. C1 Univ Western Ontario, CIHR Grp Skeletal Dev & Remodeling, Div Oral Biol, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. UCL, Ctr Rheumatol, London, England. Royal Brompton Hosp, Interstitial Lung Dis Unit, Imperial Coll Sci Technol & Med, London, England. Univ London Imperial Coll Sci & Technol, Dept Med, London, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Univ Westminster, London W1R 8AL, England. RP Leask, A (reprint author), Univ Western Ontario, CIHR Grp Skeletal Dev & Remodeling, Div Oral Biol, Schulich Sch Dent, Dent Sci Bldg, London, ON N6A 5C1, Canada. EM Andrew.Leask@schulich.uwo.ca RI Leask, Andrew/G-5217-2015 FU NICHD NIH HHS [R01 HD037490, R01 HD37490] NR 50 TC 89 Z9 93 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2005 VL 167 IS 6 BP 1699 EP 1711 DI 10.1016/S0002-9440(10)61252-7 PG 13 WC Pathology SC Pathology GA 988EE UT WOS:000233573600021 PM 16314481 ER PT J AU Howson, KM Aplin, AC Gelati, M Alessandri, G Parati, EA Nicosia, RF AF Howson, KM Aplin, AC Gelati, M Alessandri, G Parati, EA Nicosia, RF TI The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE angiogenesis; stem cells; smooth muscle; mural cells; collagen ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; SERUM RESPONSE FACTOR; STEM-CELLS; NG2 PROTEOGLYCAN; EX-VIVO; NEURONAL DIFFERENTIATION; COLLAGEN GEL; PDGF-B; ANGIOGENESIS AB Pericytes play an important role in modulating angiogenesis, but the origin of these cells is poorly understood. To evaluate whether the mature vessel wall contains pericyte progenitor cells, nonendothelial mesenchymal cells isolated from the rat aorta were cultured in a serum-free medium optimized for stem cells. This method led to the isolation of anchorage-independent cells that proliferated slowly in suspension, forming spheroidal colonies. This process required basic fibroblast growth factor (bFGF) in the culture medium, because bFGF withdrawal caused the cells to attach to the culture dish and irreversibly lose their capacity to grow in suspension. Immunocytochemistry and RT-PCR analysis revealed the expression of the precursor cell markers CD34 and Tie-2 and the absence of endothelial cell markers (CD31 and endothelial nitric oxide synthase, eNOS) and smooth muscle cell markers (alpha-smooth muscle actin, alpha-SMA). In addition, spheroid-forming cells were positive for NG2, nestin, PDGF receptor (PDGFR)-alpha, and PDGFR-beta. Upon exposure to serum, these cells lost CD34 expression, acquired alpha-SMA, and attached to the culture dish. Returning these cells to serum-free medium failed to restore their original spheroid phenotype, suggesting terminal differentiation. When embedded in collagen gels, spheroid-forming cells rapidly migrated in response to PDGF-BB and became dendritic. Spheroid-forming cells cocultured in collagen with angiogenic outgrowths of rat aorta or isolated endothelial cells transformed into pericytes. These results demonstrate that the rat aorta contains primitive mesenchymal cells capable of pericyte differentiation. These immature cells may represent an important source of pericytes during angiogenesis in physiological and pathological processes. They may also provide a convenient supply of mural cells for vascular bioengineering applications. C1 Vet Adm Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Carlo Besta Inst, Lab Neurobiol & Neuroregenerat Therapy, Milan, Italy. RP Nicosia, RF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Pathol & Lab Med, S-113-Lab,1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@med.va.gov RI Parati, Eugenio/G-8765-2011; Gelati, Maurizio/H-2110-2016 OI Gelati, Maurizio/0000-0002-4828-9849 FU NHLBI NIH HHS [HL-52585] NR 59 TC 76 Z9 80 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 2005 VL 289 IS 6 BP C1396 EP C1407 DI 10.1152/ajpcell.00168.2005 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 981RD UT WOS:000233104800006 PM 16079185 ER PT J AU Edderkaoui, M Hong, P Vaquero, EC Lee, JK Fischer, L Friess, H Buchler, MW Lerch, MM Pandol, SJ Gukovskaya, AS AF Edderkaoui, M Hong, P Vaquero, EC Lee, JK Fischer, L Friess, H Buchler, MW Lerch, MM Pandol, SJ Gukovskaya, AS TI Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreas ID CYTOSOLIC PHOSPHOLIPASE A(2); NF-KAPPA-B; NAD(P)H OXIDASE; LIPOXYGENASE INHIBITORS; SIGNAL-TRANSDUCTION; REDOX-REGULATION; LEUKOTRIENE B-4; EXPRESSION; APOPTOSIS; MITOCHONDRIAL AB The extracellular matrix (ECM) facilitates pancreatic cancer cells survival, which is of central importance for pancreatic adenocarcinoma that is highly fibrotic. Here, we show that reactive oxygen species (ROS) mediate the prosurvival effect of ECM in human pancreatic cancer cells. Fibronectin and laminin stimulated ROS production and NADPH oxidase activation in pancreatic cancer cells. Both pharmacological and molecular approaches show that fibronectin stimulated ROS production through activation of NADPH oxidase and NADPH oxidase-independent pathways and that 5-lipoxygenase (5-LO) mediates both these pathways. Analyses of the mechanisms of ROS production by ECM proteins and growth factors indicate that activation of NADPH oxidase (Nox4) is a common mechanism employed both by ECM proteins and growth factors to increase ROS in pancreatic cancer cells. We also found that Nox4 is present in human pancreatic adenocarcinoma tissues and that these tissues display membrane NADPH oxidase activity. ECM proteins and growth factors activate NADPH oxidase through different mechanisms; in contrast to ECM proteins, growth factors activate NADPH oxidase through 5-LO-independent mechanisms. Inhibition of 5-LO or NADPH oxidase with pharmacological inhibitors of these enzymes and with Nox4 or 5-LO antisense oligonucleotides markedly stimulated apoptosis in cancer cells cultured on fibronectin. Our results indicate that ROS generation via 5-LO and downstream NADPH oxidase mediates the prosurvival effect of ECM in pancreatic cancer cells. These mechanisms may play an important role in pancreatic cancer resistance to treatments and thus represent novel therapeutic targets. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Greifswald, Dept Gastroenterol Endocrinol & Nutr, Greifswald, Germany. Univ Heidelberg, Dept Gen Surg, Heidelberg, Germany. RP Gukovskaya, AS (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Dept Med, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu RI Lerch, Markus M./E-2206-2016 OI Lerch, Markus M./0000-0002-9643-8263 FU NIDDK NIH HHS [DK-59926] NR 55 TC 71 Z9 72 U1 0 U2 2 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 DEC PY 2005 VL 289 IS 6 BP G1137 EP G1147 DI 10.1152/ajpgi.00197.2005 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 983ZI UT WOS:000233270500021 PM 16037546 ER PT J AU Hazlehurst, B Sittig, DF Stevens, VJ Smith, S Hollis, JF Vogt, TM Winickoff, JP Glasgow, R Palen, TE Rigotti, NA AF Hazlehurst, B Sittig, DF Stevens, VJ Smith, S Hollis, JF Vogt, TM Winickoff, JP Glasgow, R Palen, TE Rigotti, NA TI Natural language processing in the electronic medical record: Assessing clinician adherence to tobacco treatment guidelines SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID FREE-TEXT ANALYSIS; INFORMATION; SYSTEMS AB Background: Comprehensively assessing care quality with electronic medical records (EMRs) is not currently possible because much data reside in clinicians' free-text notes. Methods: We evaluated the accuracy of MediClass, an automated, rule-based classifier of the EMR that incorporates natural language processing, in assessing whether clinicians: (1) asked if the patient smoked; (2) advised them to stop; (3) assessed their readiness to quit; (4) assisted them in quitting by providing information or medications; and (5) arranged for appropriate follow-up care (i.e., the 5A's of smoking-cessation care). Design: We analyzed 125 medical records of known smokers at each of four HMOs in 2003 and 2004. One trained abstractor at each HMO manually coded all 500 records according to whether or not each of the 5A's of smoking cessation care was addressed during routine outpatient visits. Measurements: For each patient's record, we compared the presence or absence of each of the 5A's as assessed by each human coder and by MediClass. We measured the chance-corrected agreement between the human raters and MediClass using the kappa statistic. Results: For "ask" and "assist," agreement among human coders was indistinguishable from agreement between humans and MediClass (p > 0.05). For "assess" and "advise," the human coders agreed more with each other than they did with MediClass (p > 0.01); however, MediClass performance was sufficient to assess quality in these areas. The frequency of "arrange" was too low to be analyzed. Conclusions: MediClass performance appears adequate to replace human coders of the 5A's of smoking-cessation care, allowing for automated assessment of clinician adherence to one of the most important, evidence-based guidelines in preventive health care. C1 Kaiser Permanente, Ctr Hlth Res, Portland, OR 97227 USA. Harvard Univ, Sch Med, Tobacco Res & Treatment Ctr, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Kaiser Permanente, Clin Res Unit, Denver, CO USA. RP Hazlehurst, B (reprint author), Kaiser Permanente, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM brian.hazlehurst@kpchr.org FU NCI NIH HHS [U19 CA79689] NR 34 TC 38 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2005 VL 29 IS 5 BP 434 EP 439 DI 10.1016/j.amepre.2005.08.007 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 997VE UT WOS:000234276100008 PM 16376707 ER PT J AU Keel, PK Dorer, DJ Franko, DL Jackson, SC Herzog, DB AF Keel, PK Dorer, DJ Franko, DL Jackson, SC Herzog, DB TI Postremission predictors of relapse in women with eating disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; LONG-TERM COURSE; BULIMIA-NERVOSA; ANOREXIA-NERVOSA; FOLLOW-UP; SELF-EVALUATION; RECOVERY; REMISSION; WEIGHT; SHAPE AB Objective: The authors sought to evaluate patterns and predictors of relapse among women with eating disorders. Method: Interviews were conducted biannually to annually to assess symptoms of eating disorders, axis I disorders, treatment, and psychosocial function on a weekly basis for women diagnosed with anorexia nervosa (N=136) or bulimia nervosa (N=110) and prospectively followed for 9 years. At the last follow-up, 229 (93%) of the subjects had been retained in the study group. Results: Relapse occurred in 36% of the women with anorexia nervosa and 35% of the women with bulimia nervosa. Women with intake diagnoses of anorexia nervosa, restricting subtype, tended to develop bulimic symptoms during relapse, whereas women with intake diagnoses of anorexia nervosa, binge-purge subtype, or bulimia nervosa tended to return to bulimic patterns during relapse. Greater body image disturbance contributed to a risk of relapse in both eating disorders, and worse psychosocial function increased the risk of relapse in bulimia nervosa. Conclusions: These results may explain the long-term efficacy of interpersonal therapy for bulimia nervosa and suggest that focused body image work during relapse prevention may enhance long-term recovery from eating disorders. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Keel, PK (reprint author), Univ Iowa, Dept Psychol, E11 Seashore Hall, Iowa City, IA 52242 USA. EM pamela-keel@uiowa.edu FU NIMH NIH HHS [R01 MH-38333, R01 MH-61836, R01 MH-63758] NR 36 TC 129 Z9 131 U1 6 U2 24 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 DEC PY 2005 VL 162 IS 12 BP 2263 EP 2268 DI 10.1176/appi.ajp.162.12.2263 PG 6 WC Psychiatry SC Psychiatry GA 990OX UT WOS:000233754200008 PM 16330589 ER PT J AU Wynn, JK Light, GA Breitmeyer, B Nuechterlein, KH Green, MF AF Wynn, JK Light, GA Breitmeyer, B Nuechterlein, KH Green, MF TI Event-related gamma activity in schizophrenia patients during a visual backward-masking task SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Research-in-Psychopathology CY OCT 07-10, 2004 CL St Louis, MO SP Soc Res Psychopathol ID HEMISPHERIC-ASYMMETRY; FAST OSCILLATIONS; BAND RESPONSE; SUPPRESSION; DISORDERS; MECHANISM; CORTEX AB Objective: Schizophrenia patients experience deficits in many aspects of cognition and perception. Abnormalities in gamma activity may underlie some of these deficits, including rapid processing of visual stimuli. This study examined event-related gamma range activity during a visual backward-masking task in schizophrenia patients and normal comparison subjects. Method: Event-related gamma activity was recorded in 15 normal comparison subjects and 32 schizophrenia patients. Participants had event-related gamma activity recorded while viewing 60 unmasked visual targets and 240 trials of visual backward masking. Effects of group, accuracy (correct versus incorrect), stimulus-onset asynchrony, and regional activity (left versus right hemisphere, anterior versus posterior regions) were assessed. Results: Schizophrenia patients had significantly reduced gamma activity in relation to comparison subjects during the backward-masking task. Normal comparison subjects showed significantly greater gamma activity in the right hemisphere, whereas schizophrenia patients did not show this pattern of lateralization. For the unmasked target, there was no group effect and no significant interactions in gamma-band responses. Conclusions: These results extend previous findings of abnormal gamma range activity in schizophrenia patients. Patients showed overall less gamma activity and failed to show lateralization of activity to the right hemisphere during masking, but they showed comparable levels of gamma activity to unmasked stimuli. Schizophrenia patients' poorer performance during a masking task may be partly influenced by this abnormal level and the distribution of gamma activity. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,MIRECC 210A,Bldg 210, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH-14584, MH-43292, MH-65707] NR 33 TC 51 Z9 53 U1 0 U2 1 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 DEC PY 2005 VL 162 IS 12 BP 2330 EP 2336 DI 10.1176/appi.ajp.162.12.2330 PG 7 WC Psychiatry SC Psychiatry GA 990OX UT WOS:000233754200017 PM 16330598 ER PT J AU Fine, MJ AF Fine, MJ TI Bridging the gaps between race and genetics SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2005 VL 95 IS 12 BP 2124 EP 2124 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000009 ER PT J AU Fine, MJ Ibrahim, SA Thomas, SB AF Fine, MJ Ibrahim, SA Thomas, SB TI The role of race and genetics in health disparities research SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID FACTOR-V-LEIDEN; CARE C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Minority Hlth, Pittsburgh, PA USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,Bldg 28, Pittsburgh, PA 15240 USA. EM michael.fine@med.va.gov FU NIAID NIH HHS [5K24AI001769-05, K24 AI001769]; NIMHD NIH HHS [5P60 MD00207-04, P60 MD000207] NR 23 TC 34 Z9 35 U1 0 U2 5 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 DEC PY 2005 VL 95 IS 12 BP 2125 EP 2128 DI 10.2105/AJPH.2005.076588 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000010 PM 16257933 ER PT J AU Podolsky, SH AF Podolsky, SH TI The changing fate of pneumonia as a public health concern in the 20th-century America and beyond SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; RESPIRATORY-TRACT INFECTIONS; LOBAR PNEUMONIA; UNITED-STATES; PNEUMOCOCCAL VACCINE; ANTIMICROBIAL RESISTANCE; SERUM TREATMENT; PREVENTION; MASSACHUSETTS; IMMUNIZATION AB For a brief period from the 1930s through the early 1940s, public health advocates made pneumonia a leading public health concern. Predicated on the need for antipneumococcal antiserum, but also incorporating physician reeducation, state "pneumonia control programs" were established nationwide. However, with the advent of penicillin and the sulfonamides, the pneumonia control programs soon collapsed. Pneumonia reverted to the domain of the private practitioner, which was devoid of state oversight. With the emergence of pneumococcal antibiotic resistance in the 1990s, the possibility again arose that pneumonia could become a public health concern, given the nationwide need to curb unnecessary antibiotic usage and to encourage vaccination. An understanding of the history of pneumonia's changing status could shed light on current attempts to reformulate the disease and elucidate the contested domains of private practice and public health. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02114 USA. RP Podolsky, SH (reprint author), 50 Staniford St, Boston, MA 02114 USA. EM spodolsky@partners.org FU NLM NIH HHS [1 G13 LM 07271-01] NR 112 TC 3 Z9 4 U1 2 U2 5 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 DEC PY 2005 VL 95 IS 12 BP 2144 EP 2154 DI 10.2105/AJPH.2004.048397 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000014 PM 16257952 ER PT J AU Washington, DL Villa, V Brown, A Damron-Rodriguez, J Harada, N AF Washington, DL Villa, V Brown, A Damron-Rodriguez, J Harada, N TI Racial/ethnic variations in veterans' ambulatory care use SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INVASIVE CARDIOVASCULAR PROCEDURES; ETHNIC-DIFFERENCES; RACIAL-DIFFERENCES; MEDICAL-CARE; ACCESS; SYSTEM; DISPARITIES AB Objectives: We assessed racial/ethnic variations in patterns of ambulatory care use among Department of Veterans Affairs (VA) health care-eligible veterans to determine if racial/ethnic differences in health care use persist in equal-access systems. Methods: We surveyed 3227 male veterans about their health and ambulatory care use. Results: Thirty-eight percent of respondents had not had a health care visit in the previous 12 months. Black (odds ratio [OR] = 0.5), Hispanic (OR = 0.4), and Asian/Pacific Islander veterans (OR = 0.4) were less likely than White veterans to report any ambulatory care use. Alternately, Whites (OR = 2.2) were more likely than other groups to report ambulatory care use. Being White was a greater predictor of health care use than was having fair or poor health (OR = 1.4) or functional limitations (OR = 1.5). In non-VA settings, racial/ethnic minorities were less likely to have a usual provider of health care. There was no VA racial/ethnic variation in this parameter. Conclusions: Racial/ethnic disparities in health and health care use are present among VA health care-eligible veterans. Although the VA plays an important role in health care delivery to ethnic minority veterans, barriers to VA ambulatory care use and additional facilitators for reducing unmet need still need to be investigated. C1 VA Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth & Geriatr Res, Los Angeles, CA 90024 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@med.va.gov NR 26 TC 18 Z9 18 U1 0 U2 0 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 DEC PY 2005 VL 95 IS 12 BP 2231 EP 2237 DI 10.2105/AJPH.2004.043570 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000027 PM 16257951 ER PT J AU Long, JA Polsky, D Metlay, JP AF Long, JA Polsky, D Metlay, JP TI Changes in veterans' use of outpatient care from 1992 to 2000 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-CARE; PREVENTION SERVICES; HEALTH-SERVICES; OLDER-ADULTS; MORTALITY; VA; FACILITIES; SURVIVAL; NETWORKS; PROGRAM AB Objectives: During the mid-1990s, the Veterans Health Administration (VHA) reorganized and placed greater emphasis on high-quality primary care. To determine whether the reorganization was associated with changes in patterns of outpatient VHA use, we sought to evaluate changes in characteristics of veterans who use VHA outpatient services between 1992 and 2000. Methods: We merged 2 waves of the National Survey of Veterans to determine changes in patterns of outpatient care use. We evaluated the extent to which veterans who received outpatient care received that care from the VHA. Results: The odds ratio for VHA-only outpatient care relative to non-VHA-only care in 2000 relative to 1992 was 1.75 (95% confidence interval [CI] = 1.51, 2.04), and the odds ratio for dual relative to non-VHA-only care was 1.22 (95% CI = 1.08, 1.37). Veterans who were older, had low incomes, and had no additional health insurance coverage were most likely to increase their use of VHA outpatient care. Conclusions: Our results suggest that the VHA is increasingly serving veterans who have trouble accessing the private health care system. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), Univ Penn, Sch Med, Dept Med, 1201 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu NR 27 TC 19 Z9 20 U1 1 U2 2 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 DEC PY 2005 VL 95 IS 12 BP 2246 EP 2251 DI 10.2105/AJPH.2004.061127 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000029 PM 16257943 ER PT J AU Campbell, J Kalra, MK Rizzo, S Maher, MM Shepard, JA AF Campbell, J Kalra, MK Rizzo, S Maher, MM Shepard, JA TI Scanning beyond anatomic limits of the thorax in chest CT: Findings, radiation dose, and automatic tube current modulation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; ONLINE MODULATION; LUNG-CANCER; REDUCTION AB OBJECTIVE. Our objective was to determine additional radiation dose associated with scanning beyond the anatomic limits of the thorax in chest CT protocol and to assess the effect of z-axis modulation on the additional radiation dose associated with the scanning protocol. MATERIALS AND METHODS. "Extra" images for routine chest CT were defined as those above lung apices (supraapical) and those caudal to the lowermost portion of lung parenchyma (infrapulmonary), including images obtained beyond the adrenal glands (infraadrenal). One hundred and forty-eight consecutive chest CT examinations (70 men, 78 women; age range, 15-90 years) performed September 13-25, 2003, were reviewed to determine the number of supraapical, infrapulmonary, and infraadrenal extra images. All examinations were performed using z-axis modulation (n = 70) or fixed tube current (it = 78). The CT dose index volume and dose-length product (DLP) values for the extra images were calculated. Two radiologists reviewed these extra images for pathologic findings. Student's t test was used to perform the statistical analysis. RESULTS. One hundred forty-four (97%) examinations had supraapical extra images and 145 (98%) had infrapulmonary extra images. A total of 31 additional findings were observed in extra images. Most clinically important findings were identified in patients with a history of malignancy. With z-axis modulation, the mean DLP for supraapical and infrapulmonary extra images was 39.98 mGy-cm and 132.59 mGy-cm, respectively. With fixed tube current, the mean DLP for supraapical and infrapulmonary extra images was 30.31 mGy-cm and 95.91 mGy-cm, respectively. CONCLUSION. A substantial number of extra images are acquired during chest CT that do not add clinically important information in patients with nonmalignant indications. The use of Z-axis modulation increased radiation dose for the extra images. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Natl Univ Ireland Univ Coll Cork, Dept Radiol, Cork, Ireland. RP Kalra, MK (reprint author), Emory Univ Hosp, Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM mannudeep_k_kalra@yahoo.com NR 14 TC 37 Z9 50 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 EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2005 VL 185 IS 6 BP 1525 EP 1530 DI 10.2214/AJR.04.1512 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 987IC UT WOS:000233510600022 PM 16304007 ER PT J AU Shi, AA Georgian-Smith, D Cornell, LD Rafferty, EA Staffa, M Hughes, K Kopans, DB AF Shi, AA Georgian-Smith, D Cornell, LD Rafferty, EA Staffa, M Hughes, K Kopans, DB TI Radiological reasoning: Male breast mass with calcifications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SONOGRAPHIC FEATURES; PATHOLOGICAL CORRELATION; IMAGING CHARACTERISTICS; HEMANGIOMA; CANCER; APPEARANCES; MRI; LYMPHOMA; MEN AB Objective We encountered a mammographically calcified breast mass in a 30-year-old man. It was initially thought to be comedo-type ductal carcinoma in situ because of the dense calcifications, but sonography and MRI suggested a highly vascular lesion. The final pathologic diagnosis was hemangioma. Conclusion Vascular tumors of the breast occur infrequently and are even more rare in males. The clinical and radiologic diagnosis of breast hemangioma is often difficult, but different imaging techniques, when used together, can provide important information for differential diagnosis and management. A biopsy is required. C1 Massachusetts Gen Hosp, AVON Breast Comprehens Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Georgian-Smith, D (reprint author), Massachusetts Gen Hosp, AVON Breast Comprehens Ctr, WACC 219R,15 Parkman St, Boston, MA 02114 USA. EM dgeorgiansmith@partners.org NR 30 TC 9 Z9 11 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 DEC PY 2005 VL 185 IS 6 SU S BP S205 EP S210 DI 10.2214/AJR.05.1078 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988PO UT WOS:000233613300003 PM 16304041 ER PT J AU Shi, AA Georgian-Smith, D Chew, FS AF Shi, AA Georgian-Smith, D Chew, FS TI Imaging of the male breast: Self-assessment module SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID APPEARANCES; CANCER; MEN AB The educational objectives for this self-assessment module on male breast imaging are for the participant to exercise, self-assess, and improve his or her understanding of the evaluation and management of a breast mass presenting in a man; gain familiarity with the differential diagnosis of breast masses in men and how to evaluate such lesions by imaging; gain familiarity with the sonographic features of breast cancer in men; and gain familiarity with the imaging features of vascular tumors of the breast. C1 Massachusetts Gen Hosp, AVON Breast Comprehens Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Washington, Dept Radiol, Seattle, WA 98105 USA. RP Georgian-Smith, D (reprint author), Massachusetts Gen Hosp, AVON Breast Comprehens Ctr, WACC 219R,15 Parkman St, Boston, MA 02114 USA. EM dgeorgiansmith@partners.org NR 5 TC 0 Z9 0 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 DEC PY 2005 VL 185 IS 6 SU S BP S211 EP S213 DI 10.2214/AJR.05.10781 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988PO UT WOS:000233613300004 ER PT J AU Lin, PH Bush, RL Peden, EK Zhou, W Guerrero, M Henao, EA Kougias, P Mohiuddin, I Lumsden, AB AF Lin, PH Bush, RL Peden, EK Zhou, W Guerrero, M Henao, EA Kougias, P Mohiuddin, I Lumsden, AB TI Carotid artery stenting with neuroprotection: assessing the learning curve and treatment outcome SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 57th Annual Southwestern Surgical Congress CY APR 10-12, 2005 CL San Antonio, TX DE carotid artery stenting; learning curve; complications; neuroprotection; carotid angioplasty ID MULTISPECIALTY CONSENSUS RECOMMENDATIONS; CLINICAL COMPETENCE STATEMENT; HIGH-RISK PATIENTS; RANDOMIZED-TRIAL; COMPUTER-SIMULATION; ENDARTERECTOMY; ANGIOPLASTY; STENOSIS; BIVALIRUDIN; EXPERIENCE AB Purpose: Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative in high-risk patients with carotid stenosis. The purpose of this study was to assess the effect of the learning curve oil treatment complications and the clinical outcomes of CAS. Methods: Clinical variables and treatment outcomes of 200 consecutive CAS procedures in 182 patients (mean age 72 years) with carotid stenosis >= 70% during a 40-month period were analyzed. Four sequential groups (groups I, II, III, and TV) of 50 consecutive interventions were compared with regard to technical Success, periprocedural complications, and treatment Outcomes. Results: Treatment indications and relevant risk factors were similar among the 4 groups. The overall technical success and combined 30-day stroke and death rates were 98% and 2.5%, respectively. An increase in the technical success rate was noted in the latter 3 groups compared with group I (P < .05). Total procedural time and contrast volume were significantly higher in group I compared with the latter 3 groups (P < .05). The intraoperative anticoagulation regimen was changed from intravenous heparin combination to bivalirudin after the first 54 patients, which resulted in decreased bleeding, complications in groups III and IV (P = 0.03) compared with the first group. The 30-day stroke and death rate in groups I and II were 8% and 2%, respectively, and was decreased significantly in groups III and IV (0% and 0%, respectively, P < .05). A Cox regression model identified procedural volume (P = .03) as a predictor of decreased complication rate. Conclusions: CAS with neuroprotection can provide excellent treatment Outcomes. Our experience demonstrates a procedure-associated learning curve as evidenced by decreased procedure-related complications, fluoroscopic time, and contrast volume occurring with increased physician experience. Procedural success was also enhanced partly by endovascular device refinement and ail improved anticoagulation regimen. Successful CAS Outcomes can be achieved once physicians overcome the initial procedure-related learning curve. (c) 2005 Excerpta Medica Inc. All rights reserved. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston Vet Adm Med Ctr, 2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 31 TC 60 Z9 60 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2005 VL 190 IS 6 BP 850 EP 857 DI 10.1016/j.amsjurg.2005.08.008 PG 8 WC Surgery SC Surgery GA 990RB UT WOS:000233759800006 PM 16307933 ER PT J AU Dong, HY Scadden, DT de Leval, L Tang, ZQ Isaacson, PG Harris, NL AF Dong, HY Scadden, DT de Leval, L Tang, ZQ Isaacson, PG Harris, NL TI Plasmablastic lymphoma in HIV-positive patients - An aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-31, 2000 CL New Orleans, LA SP US & Canadian Acad Pathol DE plasmablastic lymphoma; myeloma; B-cell lymphoma; HIV; EBV; HHV8 ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SARCOMA-ASSOCIATED HERPESVIRUS; PRIMARY EFFUSION LYMPHOMA; B-CELL LYMPHOMAS; KAPOSIS-SARCOMA; MULTIPLE-MYELOMA; ANAPLASTIC MYELOMA; DNA-SEQUENCES; LYMPHOPROLIFERATIVE DISORDER; AIDS AB AIDS-associated aggressive B-cell lymphomas often have plasmacytoid features. Plasma cell neoplasms in HIV patients were commonly described to have atypical morphology and an aggressive clinical course in the literature. We reviewed 14 cases of neoplasms with marked plasmacytic differentiation in HIV-positive patients to determine their clinicopathologic features. Of these, 13 of 14 had homogeneous morphology and were generally CD45+, CD20-, PAX-5-, and CD138+. All were positive for Epstein-Barr virus-encoded RNA (EBER) but lacked EBV late membrane proteins (LMP). Human herpes virus 8 (HHV8) DNA was detected in 6 of 10 cases by nested PCR, but HHV8 latent nuclear antigen (LNA) was absent. The 13 patients ranged in age from 28 to 44 years (median, 41 years) (11 male patients; 2 female patients). All patients had extramedullary and 11 of 13 had extranodal tumor at the initial presentation; 2 had distant marrow involvement. The most commonly involved location was the oral cavity (6 of 13 cases), followed by bone and soft tissue (4 of 13), and the gastrointestinal tract (3 of 13). All I I patients with follow-up died within 34 months (median, 7 months). The 14th patient who had a nodal disease with more undifferentiated morphology and expression of the HHV8 LNA protein was alive without disease at last follow-up (> 72 months), probably representing a novel HHV8+ lymphoma. We conclude that most plasmacytic tumors in HIV-positive individuals are extramedullary, clinically aggressive EBV+ tumors identical to plasmablastic lymphoma that does not have the clinical features of plasma cell lymphoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02115 USA. UCL, Dept Pathol, London, England. RP Dong, HY (reprint author), Genzyme Genom, 521 W 57th St, New York, NY 10019 USA. EM henry.dong@genzyme.com FU NCI NIH HHS [T32CA-09216 D20] NR 44 TC 109 Z9 115 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 DEC PY 2005 VL 29 IS 12 BP 1633 EP 1641 DI 10.1097/01.pas.0000173023.02724.1f PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 987TF UT WOS:000233539500010 PM 16327436 ER PT J AU Kawahara, T Shimizu, I Ohdan, H Zhao, G Sykes, M AF Kawahara, T Shimizu, I Ohdan, H Zhao, G Sykes, M TI Differing mechanisms of early and late B cell hyporesponsiveness induced by mixed chimerism SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE alpha Gal; B cell; mixed chimerism; natural antibody; tolerance ID BONE-MARROW TRANSPLANTATION; ANTIBODY-PRODUCING CELLS; IMMUNOGLOBULIN MU-CHAIN; CD4(+) T-CELLS; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; SELF-TOLERANCE; B-1 CELLS; GAL-ALPHA-1,3GAL EPITOPES; CLONAL DELETION; TRANSGENIC MICE AB Mixed hematopoietic chimerism induced via nonmyeloablative bone marrow transplantation (BMT) leads to unresponsiveness of anti-Gal alpha 1,3Gal beta 1,4G1cNAc (Gal) natural antibody (NAb)-producing cells in alpha 1,3-galactosyltransferase deficient (GalT(-/-)) mice. We analyzed the mechanisms of anti-Gal-producing B cell unresponsiveness induced by Gal(+/+) BMT. C57BL/6 (B6) GalT(-/-) mice received 3Gy whole-body irradiation and BMT from B6-CD45 congenic mice. BMT led to marked reductions in serum anti-Gal IgM levels and in the numbers of splenic anti-Gal-producing cells by 2 weeks post-BMT. B cells with anti-Gal Ig receptors were present in the spleens of 2-week but not 12-week chimeras. In vitro studies and adoptive transfer studies using B6 GalT(-/-)B cell-deficient recipients showed that B cell hyporesponsiveness to Gal at 2 weeks, but not 12 weeks, depended on persistent Gal antigen. Thus, pre-existing B-1 cells are anergic when there is continuous exposure to Gal, whereas long-term unresponsiveness does not require persistent antigen, implicating clonal deletion and/or receptor editing. These results have implications for the potential use of mixed hematopioetic chimerism as an approach to performing organ transplantation in recipients with pre-existing anti-donor IgM antibodies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646] NR 44 TC 19 Z9 19 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 DEC PY 2005 VL 5 IS 12 BP 2821 EP 2829 DI 10.1111/j.1600-6143.2005.01121.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 985WW UT WOS:000233410400003 PM 16302994 ER PT J AU Peyton, DH Burgess, SJ Andrews, S Liebman, K Kelly, JX Riscoe, M AF Peyton, David H. Burgess, Steven J. Andrews, Simeon Liebman, Katherine Kelly, Jane Xu Riscoe, Michael TI Reversed chloroquines: Molecules designed to reverse the resistance to CQ found in Plasmodium falciparum malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Peyton, David H.; Burgess, Steven J.; Andrews, Simeon; Liebman, Katherine] Portland State Univ, Portland, OR 97207 USA. [Kelly, Jane Xu; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 92 BP 31 EP 31 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000093 ER PT J AU LaRocque, RC Breiman, RF Aw, MD Morey, RE Janan, FA Hayes, JM Hossain, MA Brooks, WA Levett, PN AF LaRocque, Regina C. Breiman, Robert F. Aw, Mary D. Morey, Roger E. Janan, Firdous Ara Hayes, John Mosely Hossain, M. Anowar Brooks, W. Abdullah Levett, Paul N. TI Leptospirosis as a cause of febrile illness during an outbreak of dengue fever in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [LaRocque, Regina C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Breiman, Robert F.; Brooks, W. Abdullah] ICDDR B, Ctr Hlth & Populat Res, Dhaka, Bangladesh. [Aw, Mary D.; Morey, Roger E.; Levett, Paul N.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Janan, Firdous Ara] Dhaka Med Coll Hosp, Dhaka, Bangladesh. [Hayes, John Mosely] Ctr Dis Control & Prevent, San Juan, PR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 167 BP 56 EP 56 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000168 ER PT J AU Esparza, EYO Bonilla, DL Melby, PC Travi, BL AF Osorio Esparza, Elvia Y. Bonilla, Diana L. Melby, Peter C. Travi, Bruno L. TI Estrogen-mediated nitric oxide production is associated with a favorable clinical and parasitological response to Leishmania during pregnancy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Osorio Esparza, Elvia Y.; Bonilla, Diana L.] CIDEIM, Cali Valle Del Cauca, Colombia. [Melby, Peter C.; Travi, Bruno L.] Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 310 BP 102 EP 103 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000309 ER PT J AU Bonilla, DL Travi, BL Esparza, EYO AF Bonilla, Diana L. Travi, Bruno L. Osorio Esparza, Elvia Y. TI The role of neutrophils in American Cutaneous Leishmaniasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Bonilla, Diana L.; Osorio Esparza, Elvia Y.] CIDEIM, Cali Valle Del Cauca, Colombia. [Travi, Bruno L.] S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 312 BP 103 EP 103 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000311 ER PT J AU Esparza, EYO Bonilla, DL Peniche, AG Travi, BL AF Osorio Esparza, Elvia Y. Bonilla, Diana L. Peniche, Alex G. Travi, Bruno L. TI Congenital transmission in experimental leishmaniasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Osorio Esparza, Elvia Y.; Bonilla, Diana L.; Peniche, Alex G.] CIDEIM, Cali Valle Del Cauca, Colombia. [Travi, Bruno L.] S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 311 BP 103 EP 103 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000310 ER PT J AU Andrews, SS Burgess, SJ Selzer, A Kelly, JX Riscoe, M Peyton, DH AF Andrews, Simeon S. Burgess, Steven J. Selzer, Audrey Kelly, Jane Xu Riscoe, Michael Peyton, David H. TI Synthesis and evaluation of antimalarials formed by linking chloroquine to dibenzylamines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Andrews, Simeon S.; Burgess, Steven J.; Selzer, Audrey; Peyton, David H.] Portland State Univ, Portland, OR 97207 USA. [Kelly, Jane Xu; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 342 BP 113 EP 113 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000341 ER PT J AU Burgess, SJ Andrews, SS Selzer, A Kelly, JX Riscoe, M Peyton, DH AF Burgess, Steven J. Andrews, Simeon S. Selzer, Audrey Kelly, Jane Xu Riscoe, Michael Peyton, David H. TI Diphenylamino-modified Chloroquines that are effective against Chloroquine resistant malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Burgess, Steven J.; Andrews, Simeon S.; Selzer, Audrey; Peyton, David H.] Portland State Univ, Portland, OR 97207 USA. [Kelly, Jane Xu; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 341 BP 113 EP 113 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000340 ER PT J AU Smilkstein, MJ Riscoe, M AF Smilkstein, Martin J. Riscoe, Michael TI Antimalarial drug resistance testing with affordable, field-feasible technology SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Smilkstein, Martin J.; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 366 BP 121 EP 121 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000365 ER PT J AU Rollenhagen, J Kalsy, A John, M Harris, J LaRocque, R Qadri, F Calderwood, S Cerda, F Taylor, R Ryan, ET AF Rollenhagen, Julianne Kalsy, Anuj John, Manohar Harris, Jason LaRocque, Regina Qadri, Firdausi Calderwood, Stephen Cerda, Francisca Taylor, Ronald Ryan, Edward T. TI Protective immunity induced by transcutaneous immunization with Vibrio cholerae toxin CO-REGULATED pilus a (TcpA) antigen SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Rollenhagen, Julianne; Kalsy, Anuj; John, Manohar; Harris, Jason; Calderwood, Stephen; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Cerda, Francisca; Taylor, Ronald] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 575 BP 189 EP 190 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000574 ER PT J AU Rollenhagen, J Kalsy, A John, M Harris, J LaRocclue, R Qadri, F Calderwood, S Cerda, F Taylor, R Ryan, ET AF Rollenhagen, Julianne Kalsy, Anuj John, Manohar Harris, Jason LaRocclue, Regina Qadri, Firdausi Calderwood, Stephen Cerda, Francisca Taylor, Ronald Ryan, Edward T. TI Human-passaged hyperinfectivity of Vibrio cholerae can be modeled by growth in the infant mouse SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Rollenhagen, Julianne; Kalsy, Anuj; John, Manohar; Harris, Jason; LaRocclue, Regina; Calderwood, Stephen; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Cerda, Francisca; Taylor, Ronald] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 574 BP 189 EP 189 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000573 ER PT J AU Schwartz, BS Harris, JB Khan, AI Larocclue, RC Sack, DA Luby, SP Qadri, F Calderwood, SB Faruque, ASG Ryan, ET AF Schwartz, Brian S. Harris, Jason B. Khan, Ashraful I. Larocclue, Regina C. Sack, David A. Luby, Stephen P. Qadri, Firdausi Calderwood, Stephen B. Faruque, Abu S. G. Ryan, Edward T. TI Diarrheal epidemics in Dhaka, Bangladesh during three consecutive floods - 1988, 1998, and 2004 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Schwartz, Brian S.; Harris, Jason B.; Larocclue, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khan, Ashraful I.; Sack, David A.; Luby, Stephen P.; Qadri, Firdausi; Faruque, Abu S. G.] ICDDR B Ctr Hlth & Populat Res, Dhaka, Bangladesh. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 573 BP 189 EP 189 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000572 ER PT J AU Harris, JB Baresch-Bernal, A Alam, A LaRocque, RC Qadri, F Calderwood, SB Breiman, RF Brooks, WA Handfield, M Rollins, S Ryan, ET AF Harris, Jason B. Baresch-Bernal, Andrea Alam, Ashfaqul LaRocque, Regina C. Qadri, Firdausi Calderwood, Stephen B. Breiman, Robert F. Brooks, W. Abdullah Handfield, Martin Rollins, Sean Ryan, Edward T. TI Application of in vivo induced antigen technology (IVIAT) to Salmonella enterica serotype typhi: Identification of pagc as a marker of S-typhi infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Harris, Jason B.; Baresch-Bernal, Andrea; LaRocque, Regina C.; Calderwood, Stephen B.; Rollins, Sean; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alam, Ashfaqul; Qadri, Firdausi; Brooks, W. Abdullah] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Breiman, Robert F.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Handfield, Martin] Univ Florida, Coll Dent, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 577 BP 190 EP 190 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000576 ER PT J AU Kelly, JX Cooper, R Johnson, R Janowsky, A Smilkstein, M Winter, R Riscoel, M AF Kelly, Jane X. Cooper, Roland Johnson, Robert Janowsky, Aaron Smilkstein, Martin Winter, Rolf Riscoel, Mike TI Unique features of acridone derivatives as quinoline-resistance reversal agents against Plasmodium falciparum SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kelly, Jane X.; Johnson, Robert; Janowsky, Aaron; Smilkstein, Martin; Winter, Rolf; Riscoel, Mike] Portland VA Med Ctr, Portland, OR USA. [Cooper, Roland] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 809 BP 266 EP 266 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001232 ER PT J AU Lane, KD Kell, JX Smilkstein, M Riscoe, M Cooper, RA AF Lane, Kristin D. Kell, Jane Xu Smilkstein, Martin Riscoe, Michael Cooper, Roland A. TI The PFCRT protein has a direct role in the activity of quinoline-resistance reversal agents against Plasmodium falciparum SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Lane, Kristin D.; Cooper, Roland A.] Old Dominion Univ, Norfolk, VA USA. [Kell, Jane Xu; Smilkstein, Martin; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 815 BP 268 EP 268 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001238 ER PT J AU Smilkstein, MJ Kelly, JX Winter, R Kyle, DE Riscoe, M AF Smilkstein, Martin J. Kelly, Jane X. Winter, Rolf Kyle, Dennis E. Riscoe, Michael TI Orphenadrine as a chemosensitizer against quinoline-resistant malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Smilkstein, Martin J.; Kelly, Jane X.; Winter, Rolf; Riscoe, Michael] Portland VA Med Ctr, Portland, OR USA. [Kyle, Dennis E.] Walter Reed Army Inst Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 832 BP 274 EP 274 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001255 ER PT J AU Bennish, ML Khan, WA Begurn, M Bridges, EA Ahmed, S Saha, D Salam, MA Acheson, D Ryan, ET AF Bennish, Michael L. Khan, Wasif A. Begurn, Monira Bridges, Emily A. Ahmed, Sabeena Saha, Debasish Salam, Mohammad A. Acheson, David Ryan, Edward T. TI Low risk of hemolytic uremic syndrome (HUS) following early effective antimicrobial therapy of Shigella dysenteriae type I infection in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Bennish, Michael L.] Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. [Khan, Wasif A.; Begurn, Monira; Ahmed, Sabeena; Saha, Debasish; Salam, Mohammad A.] Int Ctr Hlth & Populat Res Bangladesh, ICDDR B, Dhaka, Bangladesh. [Bridges, Emily A.; Ryan, Edward T.] Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Boston, MA 02114 USA. [Acheson, David] Tufts Univ New England Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1098 BP 362 EP 363 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001521 ER PT J AU Yu, J Kindy, MS Ellis, BC Baatz, JE Peden-Adams, M Ellingham, TJ Wolff, DJ Fair, PA Gattoni-Celli, S AF Yu, J Kindy, MS Ellis, BC Baatz, JE Peden-Adams, M Ellingham, TJ Wolff, DJ Fair, PA Gattoni-Celli, S TI Establishment of epidermal cell lines derived from the skin of the Atlantic bottlenose dolphin (Tursiops truncatus) SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE Tursiops truncatus; bottlenose dolphin; skin; cell lines; cytokeratin ID MARINE MAMMALS; BELUGA WHALE; DELPHINAPTERUS-LEUCAS; IN-VITRO; SUSCEPTIBILITY; ORGANOCHLORINES; GENERATION AB The Atlantic bottlenose dolphin (Tursiops truncatus), a marine mammal found off the Atlantic coast, has become the focus of considerable attention because of an increasing number of mortality events witnessed in this species over the last several years along the southeastern United States. Assessment of the impact of environmental stressors on bottlenose dolphins (BND) has been difficult because of the protected status of these marine mammals. The studies presented herein focused on establishing epidermal cell cultures and cell lines as tools for the in vitro evaluation of environmental stressors on BND skin. Epidermal cell cultures were established from skin samples obtained from Atlantic BND and subjected to karyotype analysis. These cultures were further characterized using immunohistochemical methods demonstrating expression of cytokeratins. By two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), we observed that the proteomic profile of BND skin tissue samples shared distinct similarities with that of skin-derived cultures. Epidermal cell cultures were transfected with a plasmid encoding the SV40 small t- and large T-antigens, as well as the neomycin-resistance gene. Five neomycin-resistant clones were isolated and expanded, and all of them proliferated at a faster rate than nontransfected BND epidermal cultures, which exhibited signs of senescence. Cell lysates prepared from two transfected clones were shown to express, by Western blot analysis, both SV40 tumor antigens. These experimental results are consistent with the concept that transfected clones expressing SV40 tumor antigens represent immortalized BND cell lines. Epidermal cell lines derived from Tursiops truncatus will provide a unique tool for studying key features of the interaction occurring between dolphins and the environment in which they live at their most crucial interface: the skin. (c) 2005 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Inst Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. NOAA, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC USA. RP Gattoni-Celli, S (reprint author), Med Univ S Carolina, Dept Radiat Oncol, Strom Thurmond Biomed Res Bldg,Room 338C,114 Doug, Charleston, SC 29403 USA. EM gattonis@musc.edu OI Baatz, John/0000-0001-5870-1000 NR 24 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD DEC PY 2005 VL 287A IS 2 BP 1246 EP 1255 DI 10.1002/ar.a.20266 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA 989VJ UT WOS:000233701700010 PM 16281302 ER PT J AU Rathmell, JP Ballantyne, JC AF Rathmell, JP Ballantyne, JC TI Local anesthetics for the treatment of neuropathic pain: On the limits of meta-analysis SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID TRIALS C1 Univ Vermont, Coll Med, Fletcher Allen Hlth Care Ctr Pain Med, Burlington, VT USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Ctr, Boston, MA 02115 USA. RP Rathmell, JP (reprint author), Ctr Pain Med, 62 Tilley Dr, S Burlington, VT 05403 USA. EM james.rathmell@uvm.edu NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2005 VL 101 IS 6 BP 1736 EP 1737 DI 10.1213/01.ANE.0000184194.99110.80 PG 2 WC Anesthesiology SC Anesthesiology GA 987IU UT WOS:000233512400033 PM 16301252 ER PT J AU Barnet, CS Louis, DN Kohane, DS AF Barnet, CS Louis, DN Kohane, DS TI Tissue injury from tricyclic antidepressants used as local anesthetics SO ANESTHESIA AND ANALGESIA LA English DT Article ID SCIATIC-NERVE BLOCKADE; AMITRIPTYLINE; BUPIVACAINE; MYOTOXICITY; TETRODOTOXIN; DURATION; PAIN AB Neurotoxicity has been reported with tricyclic antidepressants (TCAs) used as local anesthetics. We examined the hypothesis that TCAs cause tissue injury, particularly myotoxicity, as occurs with many local anesthetics. Animals were given sciatic nerve injections with 0-80 mM doxepin, amitriptyline, or bupivacaine (1.5 mL, for histological studies, 0.3 mL, for neurobehavioral studies). Four days after injection, the TCAs caused ischemic tissue injury. Subcutaneous tissue showed expansion and hardening, with hemorrhage and adhesion to overlying skin. Muscle was diffusely pale. Histopathology showed coagulative necrosis of muscle and surrounding soft tissues, with thrombus formation in vasculature near affected areas. These findings were much reduced with bupivacaine. TCA-injected and bupivacaine-injected animals also developed characteristic local anesthetic myotoxicity. Amitriptyline proved less potent than bupivacaine as a local anesthetic: the concentrations required to provide 100 min of nerve block were 20 mM and 3 mM, respectively. Some animals receiving large concentrations of amitriptyline developed spontaneous recrudescence of nerve blockade or had irreversible nerve blockade, both of which may reflect nerve injury. Neither finding occurred in animals injected with bupivacaine. TCAs do not appear to offer any advantages over conventional local anesthetics and do appear to risk substantially increased toxicity. C1 Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol & Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Pediat Intens Care Unit, Ellison 317 ,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM00684] NR 23 TC 16 Z9 16 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2005 VL 101 IS 6 BP 1838 EP 1843 PG 6 WC Anesthesiology SC Anesthesiology GA 987IU UT WOS:000233512400051 PM 16301270 ER PT J AU Abadie, JM Blassingame, CL Bankson, DD AF Abadie, JM Blassingame, CL Bankson, DD TI Albumin Cobalt Binding assay to rule out acute coronary syndrome SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE ischemia modified albumin; cobalt binding assay; acute coronary syndrome ID ACUTE MYOCARDIAL-INFARCTION; ISCHEMIA-MODIFIED ALBUMIN; EMERGENCY ROOM PATIENTS; HUMAN SERUM-ALBUMIN; CREATINE-KINASE-MB; CHEST-PAIN; MISSED DIAGNOSES; CARE; MULTICENTER; MARKER AB The purpose of this study was to validate the Albumin Cobalt Binding (ACB((R))) assay at the Seattle Veterans Affairs (VA) Hospital to determine if it would provide an earlier rule-out of acute coronary syndrome (ACS) in patients, compared to current use of cardiac injury markers. This study compares the distribution of ischemia modified albumin (IMA) values of our patient population to those provided by the kit manufacturer. IMA values were determined photometrically on a Roche Modular Analytical System on 200 subjects: 69 subjects not experiencing chest pain (normals), 78 subjects presenting to the emergency room (ER) with chest pain whose initial and subsequent troponin results were negative (non-converters), and 53 subjects presenting to the ER with chest pain whose initial troponin result was negative but subsequent troponin results were positive (converters). Based on the relationships between IMA values in the initial samples from the non-converters and converters, we constructed a ROC curve to identify an optimum IMA rule-out value. The IMA values (mean +/- SD) for the normals, non-converters, and converters were 89 +/- 7.1, 100 +/- 13.9, and 126 +/- 14.1 U/ml, respectively, and each mean was statistically different from the means of the other groups. The ROC curve comparing converters and non-converters showed an area of 0.89 (p < 0.001) compared to the line of identity. An IMA cut-off of 97 U/ml gives a 98% sensitivity and 45% specificity and may be the best decision point to differentiate between these groups in our population. Nine of 78 non-converters were classified as having unstable angina. In conclusion, the ACB assay has a strong negative predictive value and sensitivity in our population for predicting the troponin results at 6 to 24 hr post-presentation. Because ACB results may be facility- and instrument-dependent, each facility should conduct an independent ROC analysis to determine the optimal IMA rule-out level. The ACB assay, when used in conjunction with cardiac injury markers and assessment of unstable angina, holds promise in reducing inappropriate low-risk hospital admissions and improving the clinical management of patients with chest pain. C1 Univ Washington, Med Ctr, Dept Lab Med, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Abadie, JM (reprint author), Univ Washington, Med Ctr, Dept Lab Med, NW 120, Seattle, WA 98105 USA. EM judeabadie@medscape.com NR 33 TC 19 Z9 30 U1 0 U2 2 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD WIN PY 2005 VL 35 IS 1 BP 66 EP 72 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 906PS UT WOS:000227654800009 PM 15830711 ER PT J AU Markus, TM Tsai, SY Bollnow, MR Farrer, RG O'Brien, TE Kindler-Baumann, DR Rausch, M Rudin, M Wiessner, C Mir, AK Schwab, ME Kartje, GL AF Markus, TM Tsai, SY Bollnow, MR Farrer, RG O'Brien, TE Kindler-Baumann, DR Rausch, M Rudin, M Wiessner, C Mir, AK Schwab, ME Kartje, GL TI Recovery and brain reorganization after stroke in adult and aged rats SO ANNALS OF NEUROLOGY LA English DT Article ID MONOCLONAL-ANTIBODY IN-1; NOGO-A; FUNCTIONAL RECOVERY; CORTICAL LESION; MOTOR CORTEX; PLASTICITY AB Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke. One unique therapy that improves recovery after stroke is neutralization of the neurite inhibitory protein Nogo-A. Here, we show, in a clinically relevant model, improved functional recovery and brain reorganization in the aged and adult rat when delayed anti-Nogo-A therapy is given after ischemic injury. These results support the efficacy of Nogo-A neutralization as treatment for ischemic stroke, even in the aged animal and after a 1-week delay, and implicate neuronal plasticity from unlesioned areas of the central nervous system as a mechanism for recovery. C1 Loyola Univ, Neurosci & Aging Inst, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol & Res Serv, Hines, IL 60141 USA. Loyola Univ, Ctr Stat Consulting, Dept Math & Stat, Chicago, IL 60611 USA. Novartis Pharma AG, Nervous Syst Res, Neuroregenerat Unit, Basel, Switzerland. Univ Zurich, Brain Res Inst, Zurich, Switzerland. Swiss Fed Inst Technol, Dept Biol, Zurich, Switzerland. Loyola Univ, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. RP Kartje, GL (reprint author), Edward Hines Jr Vet Adm Hosp, Neurol Serv 127, Bldg 1,Room F201,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM wendy.kartje@med.va.gov RI Rudin, Markus/F-2417-2010; Schwab, Martin/B-6818-2016 FU NINDS NIH HHS [NS 40960, R56 NS040960]; RRD VA [I01 RX000828] NR 20 TC 83 Z9 87 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 BP 950 EP 953 DI 10.1002/ana.20676 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900018 PM 16315284 ER PT J AU Chen, HL Jacobs, E Schwarzschild, MA McCullough, ML Calle, EE Thun, MJ Ascherio, A AF Chen, HL Jacobs, E Schwarzschild, MA McCullough, ML Calle, EE Thun, MJ Ascherio, A TI Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID SODIUM-SALICYLATE; NEUROPROTECTION; ACTIVATION; ASPIRIN; MODEL AB We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson's disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (p trend=0.03). No association was found between the use of aspirin, other nonsteroidal and inflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NINDS NIH HHS [NS 48468] NR 18 TC 239 Z9 248 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 BP 963 EP 967 DI 10.1002/ana.20682 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900021 PM 16240369 ER PT J AU Ng, AK Li, S Recklitis, C Neuberg, D Chakrabarti, S Silver, B Diller, L AF Ng, AK Li, S Recklitis, C Neuberg, D Chakrabarti, S Silver, B Diller, L TI A comparison between long-term survivors of Hodgkin's disease and their siblings on fatigue level and factors predicting for increased fatigue SO ANNALS OF ONCOLOGY LA English DT Article DE cancer survivors; fatigue; Hodgkin's disease; late effects ID QUALITY-OF-LIFE; CHILDHOOD-CANCER SURVIVOR; CORONARY-ARTERY-DISEASE; PSYCHOSOCIAL ADAPTATION; MEDIASTINAL IRRADIATION; GENERAL-POPULATION; RADIATION-THERAPY; CONTROLLED-TRIAL; RADIOTHERAPY; MORTALITY AB Purpose: To compare the level of fatigue in survivors of Hodgkin's disease and their siblings, and to explore factors associated with increased fatigue. Methods: Survivors of Hodgkin's disease 5 years or more from diagnosis and their siblings completed a questionnaire study. Fatigue level was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) instrument, with lower scores reflecting increased fatigue. Multiple regression models were used to identify factors associated with fatigue level in the two populations. Results: Five hundred and eleven survivors (median age 44 years; range 16-82) and 224 siblings (median age 44 years; range 16-79) returned the completed questionnaire. The response rates were 61% and 58%, respectively. Compared with siblings, survivors were significantly more likely to report the presence of cardiac disease (26% versus 16%; P = 0.001) and hypothyroidism (65% versus 3%; P < 0.001), and had a significantly lower mean FACIT-F score (40.7 and 42.2; P = 0.05). On multivariable analysis, factors significantly associated with increased fatigue in survivors were reports of cardiac disease (P < 0.001), psychiatric condition (P < 0.001), history of tobacco use (P = 0.004) and low exercise frequency (P = 0.03). For siblings, the only independent factor associated with increased fatigue was low exercise frequency (P = 0.03). Conclusions: Survivors of Hodgkin's disease were more fatigued than their siblings. The difference was modest but statistically significant. The significant association between fatigue and cardiac disease suggests the importance of screening for underlying cardiac dysfunction in survivors with symptoms of fatigue. The association between fatigue and smoking history may be due to exacerbation of late medical complications of Hodgkin's disease by tobacco use. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB 1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 45 TC 37 Z9 38 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2005 VL 16 IS 12 BP 1949 EP 1955 DI 10.1093/annonc/mdi407 PG 7 WC Oncology SC Oncology GA 987AA UT WOS:000233489600015 PM 16227316 ER PT J AU Kieff, DA Busaba, NY AF Kieff, DA Busaba, NY TI Efficacy of montelukast in the treatment of nasal polyposis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE chronic sinusitis; eosinophilia; montelukast; nasal polyposis; rhinitis; symptom score ID SEASONAL ALLERGIC RHINITIS; CHRONIC RHINOSINUSITIS; DOUBLE-BLIND; ASTHMA; SINUSITIS; SYMPTOMS AB Objectives: Twenty-four consecutive patients with symptomatic nasal polyposis and nonallergic or perennial rhinitis who were undergoing chronic nasal steroid therapy were prospectively evaluated for response to adjunctive oral montelukast sodium therapy. Methods: The patients were undergoing daily intranasal steroid sprays for a minimum of 6 months before being started on montelukast sodium 10 mg by mouth per day for 3 months while intranasal steroids were continued. The patients were given a validated symptom score survey at the start and end of therapy, with a lower score indicating fewer symptoms. The nasal polyps were submitted to biopsy before and after treatment to determine their degree of eosinophilia. Eosinophilia was graded in a blinded fashion by an independent pathologist on a scale of 0 to 3, with 3 being severe. Patients with seasonal allergies were excluded, and the studied patients were treated during the winter season to avoid confounding by potential seasonal allergic responses. Results: The patients tended to improve on montelukast therapy in terms of their symptom scores and polyp eosinophil counts. The symptoms improved in 17 patients (71%) and remained the same or worsened in 7 patients (29%). The symptom score for the group improved from a pretreatment value of 33.4 (SD, 7.73) to a posttreatment value of 23.3 (SD, 13.73; p <.001). In addition, the eosinophilia score improved from 2.3 (SD, 0.68) to 1.5 (SD, 0.82; p <.01). The improvement was most noticeable in the patients with perennial allergies. Conclusions: These results suggest that montelukast appears to be beneficial for some patients with nasal polyposis. Patients with perennial allergies and nasal polyposis seem more likely to respond to the treatment than those with nonallergic nasal polyposis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Vanguard Med Associates, Div Otolaryngol, Boston, MA USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charlest St, Boston, MA 02114 USA. NR 26 TC 25 Z9 28 U1 1 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2005 VL 114 IS 12 BP 941 EP 945 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 993IZ UT WOS:000233949100009 PM 16425561 ER PT J AU O'Brien, PKH Kucharczuk, JC Marshall, MB Friedberg, JS Chen, Z Kaiser, LR Shrager, JB AF O'Brien, PKH Kucharczuk, JC Marshall, MB Friedberg, JS Chen, Z Kaiser, LR Shrager, JB TI Comparative study of subxiphoid versus video-thoracoscopic pericardial "'window" SO ANNALS OF THORACIC SURGERY LA English DT Article ID PERCUTANEOUS CATHETER DRAINAGE; SURGICAL-MANAGEMENT; CARDIAC-TAMPONADE; EFFUSION; DIAGNOSIS; DISEASE; RESECTION; MALIGNANCY AB Background. It remains undefined whether surgical subxiphoid drainage or thoracoscopic pericardial "window" is the optimal operative approach to pericardial effusion. We hypothesized that the true window into the pleural space created by the latter might improve the duration of freedom from recurrent effusion. Methods. We conducted a retrospective chart review of indications, preoperative and intraoperative variables, morbidity, recurrence, and survival. Results. Fifty-six patients underwent the subxiphoid procedure and 15 underwent the thoracoscopic procedure. Echocardiographic evidence of tamponade was present before 8 of 10 thoracoscopic procedures (80%) and 43 of 56 subxiphoid procedures (81%) for which descriptions of hemodynamics were available. In addition, non-pericardial procedures were performed in 10 (67%) and 18 (32%) patients, respectively (p = 0.020). Anesthesia time was longer at thoracoscopy (117.1 +/- 32.4 vs 81.1 +/- 25.5 minutes; p < 0.001). Procedural morbidity was higher after thoracoscopy (4 [27%] vs 1 [2%]; p = 0.006), but was generally minor. Hospital mortality tended to be higher after the subxiphoid procedure (7 [13%] vs 0 [0%]; P = 0.332), but none of the deaths was procedure-related. Follow-up was complete for 65 patients (92%). Recurrence occurred in 1 thoracoscopy patient (8%) and 5 subxiphoid patients (10%) (p = 1.000). Mean time to recurrence by Kaplan-Meier analysis trends were longer after thoracoscopy (36.1 vs 11.4 months; p = 0.16), and multivariate analysis identified the thoracoscopic approach as an independent predictor of freedom from recurrence (relative risk, 0.41; p = 0.014). Conclusions. Operative time and minor procedural morbidity are higher with thoracoscopic pericardial window, but long-term control of effusion seemed to be better than after subxiphoid surgical drainage. C1 Univ Penn, Sch Med, Sect Gen Thorac Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. RP Shrager, JB (reprint author), Hosp Univ Penn, Silverstein 6,3400 Spruce St, Philadelphia, PA 19104 USA. EM joseph.shrager@uphs.upenn.edu NR 27 TC 19 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2005 VL 80 IS 6 BP 2013 EP 2019 DI 10.1016/j.athoracsur.2005.05.059 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 993BD UT WOS:000233926800006 PM 16305836 ER PT J AU Grillo, HC Wright, CD Dartevelle, PG Wain, JC Murakami, S AF Grillo, HC Wright, CD Dartevelle, PG Wain, JC Murakami, S TI Tracheal compression caused by straight back syndrome, chest wall deformity, and anterior spinal displacement: Techniques for relief SO ANNALS OF THORACIC SURGERY LA English DT Article ID PLATE AB Background. Straight back syndrome and other causes of extreme narrowing of the space between sternal notch and vertebrae can cause critical tracheal obstruction. Additional points of compression may result from the brachiocephalic artery and from anterior vertebral displacement. Methods. Individualized surgical maneuvers are necessary to correct all points of obstruction. Techniques include sternoplasty, sternal division, reimplantation of brachiocephalic artery, correction of severe pectus excavatum, and posterior wall tracheoplasty. Results. Four patients were successfully treated by individualized techniques with complete long-term relief of critical tracheal obstruction. Conclusions. Severe tracheal compression caused by straight back syndrome and other causes of narrowed sternospinal channel is surgically correctable. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Univ Paris Sud, Marie Lannelongue Hosp, Heart Lung Transplantat, Le Plessis Robinson, France. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, 55 Fruit St, Boston, MA 02114 USA. EM pguerriero@partners.org NR 13 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2005 VL 80 IS 6 BP 2057 EP 2062 DI 10.1016/j.athoracsur.2005.05.026 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 993BD UT WOS:000233926800013 PM 16305844 ER PT J AU Akins, CW Hilgenberg, AD Vlahakes, GJ Madsen, JC MacGillivray, TE LaMuraglia, GM Cambria, RP AF Akins, CW Hilgenberg, AD Vlahakes, GJ Madsen, JC MacGillivray, TE LaMuraglia, GM Cambria, RP TI Late results of combined carotid and coronary surgery using actual versus actuarial methodology SO ANNALS OF THORACIC SURGERY LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; ARTERY-BYPASS; CARDIOPULMONARY BYPASS; VALVE-REPLACEMENT; AORTIC-VALVE; RISK-FACTORS; ENDARTERECTOMY; STROKE; REVASCULARIZATION; OUTCOMES AB Background. Controversy exists over the short-term results and long-term efficacy of concomitant coronary artery bypass grafting and carotid endarterectomy. Additionally, in this population actual versus actuarial assessment of nonfatal late events has not been previously reported. Methods. Hospital records of 500 consecutive patients having concomitant carotid endarterectomy and coronary artery bypass grafting between 1979 and 2001 were reviewed, allowing at least 1 year of follow-up on all patients. Long-term nonfatal complications were assessed by actual and actuarial methods. Results. Patient demographics revealed a mean age of 69 years; 74% (370 patients) were male; 75% (377 patients) presented with unstable coronary syndromes; 10% (50 patients) had an intraaortic balloon pump; and 66% (329 patients) were neurologically asymptomatic. Hospital mortality was 3.6% (18 patients). Significant multivariable predictors of hospital death were preoperative transient ischemic attack or myocardial infarction, and nonelective operation. Perioperative strokes were 4.6% (23 patients), of which 2.4% (12 patients) were ipsilateral and 2.2% (11 patients) were contralateral. Significant multivariable predictors of stroke were peripheral vascular disease and use of the right internal mammary artery. Ten-year actuarial survival was 43%. Ten-year actual versus Kaplan-Meier actuarial freedoms with 95% confidence limits from late events were myocardial infarction 87% (78% and 92%) versus 81% (75% and 87%); percutaneous coronary intervention 92% (85% and 96%) versus 89% (84% and 94%); reoperative coronary grafting 96% (89% and 99%) versus 94% (90% and 98%); total stroke 85% (77% and 91%) versus 82% (76% and 87%); ipsilateral stroke 90% (83% and 94%) versus 87% (82% and 92%); carotid endarterectomy 82% (73% and 88%) versus 75% (69% and 82%). Conclusions. Concomitant carotid and coronary artery surgery is safe and effective, particularly in preventing ipsilateral stroke, and neutralizes the impact of unilateral carotid stenosis on early and late stroke. Actual, not actuarial, methods more accurately represent the true risk of nonfatal late events. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vasc Surg Div, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, White 503,55 Fruit St, Boston, MA 02114 USA. EM cakins@partners.org NR 24 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2005 VL 80 IS 6 BP 2091 EP 2097 DI 10.1016/j.athoracsur.2005.05.029 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 993BD UT WOS:000233926800019 PM 16305851 ER PT J AU Shahian, DM Torchiana, DF Shemin, RJ Rawn, JD Normand, SLT AF Shahian, DM Torchiana, DF Shemin, RJ Rawn, JD Normand, SLT TI Massachusetts cardiac surgery repory card: Implications of statistical methodology SO ANNALS OF THORACIC SURGERY LA English DT Article ID BYPASS GRAFT-SURGERY; ALTERNATING LOGISTIC REGRESSIONS; NEW-YORK-STATE; MORTALITY-RATES; QUALITY IMPROVEMENT; LONGITUDINAL DATA; RISK-ADJUSTMENT; MODELS; HEALTH; ISSUES AB Background. Choice of statistical methodology may significantly impact the results of provider profiling, including cardiac surgery report cards. Because of sample size and clustering issues, logistic regression may overestimate systematic interprovider variability, leading to false outlier classification. Theoretically, the use of hierarchical models should result in more accurate representation of provider performance. Methods. Extensively validated and audited data were available for all 4,603 isolated coronary artery bypass grafting procedures performed at 13 Massachusetts hospitals during 2002. To produce the official Massachusetts cardiac surgery report card, a 19-variable predictor set and a hierarchical generalized linear model were employed. For the current study, this same analysis was repeated with the 14 predictors used in the New York Cardiac Surgery Reporting System. Two additional analyses were conducted using each set of predictor variables and applying standard logistic regression. For each of the four combinations of predictors and models, the point estimates of risk-adjusted 30-day mortality, 95% confidence or probability intervals, and outlier status were determined for each hospital. Results. Overall unadjusted mortality for coronary bypass operations was 2.19%. For most hospitals, there was wide variability in the point estimates and confidence or probability intervals of risk-adjusted mortality depending on statistical model, but little variability relative to the choice of predictors. There were no hospital outliers using hierarchical models, but there was one outlier using logistic regression with either predictor set. Conclusions. When used to compare provider performance, logistic regression increases the possibility of false outlier classification. The use of hierarchical models is recommended. C1 Massachusetts Gen Hosp, Dept Cardiac Surg, St Elizabeths Med Ctr, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Brigham & Womens Hosp,Div Cardiac Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Shahian, DM (reprint author), Caritas St Elizabeths Med Ctr, Dept Surg, 736 Cambridge St, Boston, MA 02135 USA. EM david.shahian@caritaschristi.org NR 46 TC 71 Z9 74 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2005 VL 80 IS 6 BP 2106 EP 2113 DI 10.1016/j.athoracsur.2005.06.078 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 993BD UT WOS:000233926800021 PM 16305853 ER PT J AU Strizki, JM Tremblay, C Xu, S Wojcik, L Wagner, N Gonsiorek, W Hipkin, RW Chou, CC Pugliese-Sivo, C Xiao, YS Tagat, JR Cox, K Priestley, T Sorota, S Huang, W Hirsch, M Reyes, GR Baroudy, BM AF Strizki, JM Tremblay, C Xu, S Wojcik, L Wagner, N Gonsiorek, W Hipkin, RW Chou, CC Pugliese-Sivo, C Xiao, YS Tagat, JR Cox, K Priestley, T Sorota, S Huang, W Hirsch, M Reyes, GR Baroudy, BM TI Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QT INTERVAL PROLONGATION; SCH-C SCH-351125; HIV-1 INFECTION; FUSION INHIBITOR; ENTRY INHIBITOR; IN-VITRO; SAFETY; ENFUVIRTIDE; PIPERAZINE; TARGETS AB Inhibiting human immunodeficiency virus type 1 (HIV-1) infection by blocking the host cell coreceptors CCR5 and CXCR4 is an emerging strategy for antiretroviral therapy. Currently, several novel coreceptor inhibitors are being developed in the clinic, and early results have proven promising. In this report, we describe a novel CCR5 antagonist, vicriviroc (formerly SCH-D or SCH 417690), with improved antiviral activity and pharmacokinetic properties compared to those of SCH-C, a previously described CCR5 antagonist. Like SCH-C, vicriviroc binds specifically to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1 isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity against genetically diverse and drug-resistant HIV-1 isolates and was consistently more active than SCH-C in inhibiting viral replication. This compound demonstrated synergistic anti-HIV activity in combination with drugs from all other classes of approved antiretrovirals. Competition binding assays revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C. Functional assays, including inhibition of calcium flux, guanosine 5'-[S-35] triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally, vicriviroc demonstrated diminished affinity for the human ether a-go-go related gene transcript ion channel compared to SCH-C, suggesting a reduced potential for cardiac effects. Vicriviroc represents a promising new candidate for the treatment of HIV-1 infection. C1 Schering Plough Corp, Res Inst, Dept Antiviral Therapy, Kenilworth, NJ 07033 USA. Schering Plough Corp, Res Inst, Dept Inflammat, Kenilworth, NJ 07033 USA. Schering Plough Corp, Res Inst, Dept Med Chem, Kenilworth, NJ 07033 USA. Schering Plough Corp, Res Inst, Dept Drug Metab & Pharmacokinet, Kenilworth, NJ 07033 USA. Schering Plough Corp, Res Inst, Dept Neurobiol, Kenilworth, NJ 07033 USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Monogram Biosci, San Francisco, CA 94080 USA. RP Strizki, JM (reprint author), Schering Plough Corp, Res Inst, Dept Antiviral Therapy, 2015 Galloping Hill Rd,K15,E405C-4945, Kenilworth, NJ 07033 USA. EM Julie.strizki@spcorp.com NR 26 TC 180 Z9 200 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2005 VL 49 IS 12 BP 4911 EP 4919 DI 10.1128/AAC.49.12.4911-4919.2005 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 989RS UT WOS:000233692100011 PM 16304152 ER PT J AU Strahilevitz, J Truong-Bolduc, QC Hooper, DC AF Strahilevitz, J Truong-Bolduc, QC Hooper, DC TI DX-619, a novel des-fluoro(6) quinolone manifesting low frequency of selection of resistant Staphylococcus aureus mutants: Quinolone resistance beyond modification of type II topoisomerases SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIDRUG EFFLUX TRANSPORTER; DNA GYRASE; FLUOROQUINOLONE RESISTANCE; GARENOXACIN BMS-284756; TARGET INTERACTIONS; NORA GENE; IV; CIPROFLOXACIN; EXPRESSION; PROTEIN AB DX-619, a novel des-fluoro(6) quinolone, was 16- to 32-fold, twofold, and four- to eightfold more potent than ciprofloxacin, gemifloxacin, and garenoxacin, respectively, against wild-type Staphylococcus aureus. DX-619 manifested equal fourfold increases in MIC against a common parC mutant and a common gyrA mutant and selected for mutants at up to two- to fourfold its MIC, consistent with dual-targeting properties. Of the four independent single-step mutants selected, two had new single mutations in parC (V87F and R17H), and two shared a new gyrA mutation (A26V), one with an additional deletion mutation in parE (Delta 215-7). By allelic exchange, the ParC but not the GyrA or ParE mutation was shown to be fully responsible for the resistance phenotypes, suggesting an as yet undefined mechanism of resistance operating in conjunction with type II topoisomerase mutations contributed to resistance to DX-619. Studies with purified topoisomerase IV and gyrase from S. aureus also showed that DX-619 had similar activity against topoisomerase IV and gyrase (50% stimulation of cleavage complexes concentration, 1.25 and 0.62 to 1.25 mu g/ml, respectively). Susceptibility studies with DX-619 and an array of efflux pump substrates with and without reserpine, an inhibitor of efflux pumps, suggested that resistance in DX-619-selected mutants is affected by mechanisms other than mutations in topoisomerases or known reserpine-inhibitable pumps in S. aureus and thus are likely novel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, AI 23988, R37 AI023988] NR 37 TC 15 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2005 VL 49 IS 12 BP 5051 EP 5057 DI 10.1128/AAC.49.12.5051-5057.2005 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 989RS UT WOS:000233692100031 PM 16304172 ER PT J AU Barchiesi, F Spreghini, E Santinelli, A Fothergill, AW Fallani, S Manso, E Pisa, E Giannini, D Novelli, A Cassetta, MI Mazzei, T Rinaldi, MG Scalise, G AF Barchiesi, F Spreghini, E Santinelli, A Fothergill, AW Fallani, S Manso, E Pisa, E Giannini, D Novelli, A Cassetta, MI Mazzei, T Rinaldi, MG Scalise, G TI Efficacy of caspofungin against Aspergillus terreus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PULMONARY ASPERGILLOSIS; INVASIVE ASPERGILLOSIS; ANTIFUNGAL THERAPY; AMPHOTERICIN-B; INFECTION; AGENT AB We investigated the in vitro and in vivo activities of caspofungin against Aspergillus terreus. The drug increased survival and reduced tissue fungal burden in neutropenic mice. Therefore, our data support the role of caspofungin in treating systemic infections due to this emerging pathogen. C1 Univ Policlin Marche, Ist Malattie Infett & Med Pubbl, Azienda Osped Univ, Osped Riuniti Umberto I Lancisi Salesi, I-60020 Ancona, Italy. Univ Policlin Marche, Ist Anat Patol, I-60020 Ancona, Italy. Univ Policlin Marche, Ctr Gest Presidenza Med & Chirurg, I-60020 Ancona, Italy. Univ Osped Riuniti Umberto I Lancisi Salesi, Microbiol Lab, Ancona, Italy. Univ Florence, Ist Farmacol Preclin & Clin, Florence, Italy. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Barchiesi, F (reprint author), Univ Policlin Marche, Ist Malattie Infett & Med Pubbl, Azienda Osped Univ, Osped Riuniti Umberto I Lancisi Salesi, Via Conca, I-60020 Ancona, Italy. EM l.infettive@ao-umbertoprimo.marche.it RI Spreghini, Elisabetta/G-9378-2012 NR 13 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2005 VL 49 IS 12 BP 5133 EP 5135 DI 10.1128/AAC.49.12.5133-5135.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 989RS UT WOS:000233692100044 PM 16304185 ER PT J AU Hilsabeck, RC Gouvier, WD AF Hilsabeck, RC Gouvier, WD TI Detecting simulated memory impairment: Further validation of the Word Completion Memory Test (WCMT) SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the National-Academy-of-Neuropsychology CY NOV, 1998 CL WASHINGTON, D.C. SP Natl Acad Neuropsychol DE malingering; cognitive; neuropsychological; faking bad; implicit memory ID TRAUMATIC BRAIN-INJURY; MILD HEAD-INJURY; REY 15-ITEM TEST; SUSPECT EFFORT; FIGURE TEST; VALIDITY; DEFICITS; MMPI-2; IMPLICIT AB The Word Completion Memory Test (WCMT) was developed to detect sophisticated attempts at simulating memory impairment. The primary purpose of the present study was to provide additional validity and reliability information about the WCMT. Seventy-one participants were recruited for this study: 30 normal volunteers and 11 memory-disordered patients instructed to perform their best, and 30 normal volunteers instructed to fake memory impairment. Normal volunteers were administered five tests of neuropsychological functioning and five tests of simulation to explore the convergent and divergent validity of the WCMT. Two weeks later, these participants completed all 10 measures a second time. Memory-disordered patients were administered the WCMT and two additional simulation measures as part of a comprehensive neuropsychological evaluation. The WCMT successfully discriminated simulators from nonsimulators with an overall classification accuracy of 97% and demonstrated good psychometric properties. In conclusion, the WCMT continues to show promise as a measure of simulated memory impairment. (c) 2005 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM robin.hilsabeck@med.va.gov NR 58 TC 6 Z9 6 U1 14 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2005 VL 20 IS 8 BP 1025 EP 1041 DI 10.1016/j.acn.2005.05.003 PG 17 WC Psychology, Clinical; Psychology SC Psychology GA 992LD UT WOS:000233884500006 PM 16099137 ER PT J AU Hussein, MR Haemel, AK Albert, DM Wood, GS AF Hussein, MR Haemel, AK Albert, DM Wood, GS TI Microsatellite instability and alterations of mismatch repair protein expression in choroidal melanomas SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CUTANEOUS MALIGNANT MELANOMAS; POSTERIOR UVEAL MELANOMA; CYTOGENETIC FINDINGS; ALTERED EXPRESSION; COLORECTAL-CANCER; HMLH1 EXPRESSION; MELANOCYTIC NEVI; DYSPLASTIC NEVI; FAMILY-HISTORY; HMSH2 AB Objectives: To examine choroidal melanomas for genomic instability, manifested by microsatellite instability (MSI) and mismatch repair (MMR) protein alterations, and to determine the association of these alterations with selected clinicopathological features of the tumors. Methods: Polymerase chain reaction-based microsatellite assays were applied to analyze 57 cases of choroidal melanomas using 11 microsatellite markers at 5 chromosomal regions: 1p, 2p, 4q, 9p, and 17p. Immunoperoxidase staining methods and mouse monoclonal antibodies were used to investigate the expression patterns of MMR proteins. Results: Microsatellite instability was found at the 1p, 9p, and 17p regions in these lesions with an overall prevalence of 35% (20/57). The frequency of MST ranged from 9% (1/11) to 27% (3/11), ie, low-level MSI (MSI-L). The instability was most commonly found at the 1p region (D1S2734, 55%; D1S2832, 40%; and D1S233, 20%). Two MST banding patterns, band shifts and the appearance of additional bands, were found in 10% and 90% of the unstable lesions, respectively. The average percentages of hMLH1 and hMSH2 positively stained cells were insignificantly reduced in the unstable lesions (81.7 +/- 9.3 and 76.7 +/- 16.7) as compared with the stable lesions (84.1 +/- 15.5 and 78.6 +/- 19.6; P = .62 and 0.74 for hMLH1 and hMSH2, respectively). There was no significant difference in survival between the 2 groups; however, relative to the stable subset, the unstable tumors showed a trend (P < .10) toward occurring at a younger age and having tumor cells in vascular lakes. Conclusions: The presence of MSI-L in some choroidal melanomas defines a novel genetic subset of these tumors and suggests that MSI (genomic instability) may play a role in their molecular pathogenesis. Elucidation of the underlying mechanisms for MSI will require further investigation. Clinical Relevance: Detection of the MSI-L pattern might prove to be useful as an adjunct to the conventional diagnosis of choroidal melanomas. Larger series are needed to determine whether any of the correlative trends noted in this study will achieve statistical significance. To the best of our knowledge, this study is the first to define both the MST and MMR protein expression features of choroidal melanomas. Conclusions: The presence of MSI-L in some choroidal melanomas defines a novel genetic subset of these tumors and suggests that MST (genomic instability) may play a role in their molecular pathogenesis. Elucidation of the underlying mechanisms for MST will require further investigation. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. Assiut Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt. Brown Med Sch, Providence, RI USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. EM gwood@dermatology.wisc.edu FU NIAMS NIH HHS [AR02136] NR 37 TC 8 Z9 8 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 DEC PY 2005 VL 123 IS 12 BP 1705 EP 1711 DI 10.1001/archopht.123.12.1705 PG 7 WC Ophthalmology SC Ophthalmology GA 991BS UT WOS:000233787800011 PM 16344443 ER PT J AU Chen, TC Cense, B Pierce, MC Nassif, N Park, BH Yun, SH White, BR Bouma, BE Tearney, GJ de Boer, JF AF Chen, TC Cense, B Pierce, MC Nassif, N Park, BH Yun, SH White, BR Bouma, BE Tearney, GJ de Boer, JF TI Spectral domain optical coherence tomography - Ultra-high speed, ultra-high resolution ophthalmic imaging SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CYSTOID MACULAR EDEMA; NERVE-FIBER LAYER; CENTRAL SEROUS CHORIORETINOPATHY; RETINITIS-PIGMENTOSA; DOPPLER TOMOGRAPHY; ANTERIOR SEGMENT; HIGH MYOPIA; BLOOD-FLOW; THICKNESS; HOLE AB Objective: To introduce a new ophthalmic optical coherence tomography technology that allows unprecedented simultaneous ultra-high speed and ultra-high resolution. Methods: Using a superluminescent diode source, a clinically viable ultra-high speed, ultra-high resolution spectral domain optical coherence tomography system was developed. resolution of 6 pm. Using a different source in a slightly slower configuration, single images consisting of 500 Ascans were acquired in 34 ms, allowing imaging at 29 frames per second at an axial resolution of 3.5 mu m, which is 3 times better than commercially available optical coherence tomography instruments. The amount of energy directed into the eye in both cases, 600 mu W, is less than that of the Stratus OCT3 and is safe for intrabeam viewing for up to 8 hours at the same retinal location. Results: In vivo images of the retina, the optic nerve head, and retinal blood flow were obtained at an ultra-high speed of 34.1 microseconds (ms) per A-scan, which is 73 times faster than commercially available optical coherence tomography instruments. Single images (B-scans) consisting of 1000 A-scans were acquired in 34.1 ms, allowing video rate imaging at 29 frames per second with an axial resolution of 6 pm. Using a different source in a slightly slower configuration, single images consisting of 500 Ascans were acquired in 34 ms, allowing imaging at 29 frames per second at an axial resolution of 3.5 mu m, which is 3 times better than commercially available optical coherence tomography instruments. The amount of energy directed into the eye in both cases, 600 mu W, is less than that of the Stratus OCT3 and is safe for intrabeam viewing for up to 8 hours at the same retinal location. Conclusion: Spectral domain optical coherence tomography technology enables ophthalmic imaging with unprecedented simultaneous ultra-high speed and ultrahigh resolution. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [R24 EY12877, R01 EY014975] NR 58 TC 205 Z9 213 U1 0 U2 12 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 DEC PY 2005 VL 123 IS 12 BP 1715 EP 1720 DI 10.1001/archopht.123.12.1715 PG 6 WC Ophthalmology SC Ophthalmology GA 991BS UT WOS:000233787800012 PM 16344444 ER PT J AU Shrank, W Ettner, SL Slavin, PH Kaplan, HJ AF Shrank, W Ettner, SL Slavin, PH Kaplan, HJ TI Effect of physician reimbursement methodology on the rate and cost of cataract surgery SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FEE-FOR-SERVICE; FINANCIAL INCENTIVES; VISUAL FUNCTION; CARE; OUTCOMES; PAYMENT; ORGANIZATIONS; PERFORMANCE; EXTRACTION; MORTALITY AB Objectives: To compare the effects of 2 reimbursement methodologies, fee-for-service and contact capitation, on cataract extraction rates and costs in a stable physician population with little potential for the influence of patient selection. Previous research evaluating the relationship between physician reimbursement incentives and cataract surgical rates has been limited by physician and patient selection bias. Methods: A pre-post analysis of claims and encounter data for an average of 91473 commercial beneficiaries and 14 084 Medicare beneficiaries receiving eye care from a network of ophthalmologists and optometrists in St Louis, Mo, between 1997 and 1998. The rate of cataract extractions per 1000 beneficiaries, the costs of cataract procedures, the rates of noncataract procedures, and the level of professional reimbursement for providers were compared during the final 6 months of fee-for-service physician reimbursement and the first 6 months of contact capitation. Results: Both commercial and Medicare beneficiaries were approximately one half as likely to have cataract extraction (P < .001) under contact capitation as compared with fee-for-service. Professional reimbursement increased by 8% whereas facility fees for cataract procedures decreased by approximately 45%. Cataract surgical rates were disproportionately affected when compared with other ophthalmologic procedures. During the study period, cataract surgical rates were stable in the national and Missouri traditional fee-for-service Medicare population. Conclusions: The stability of the physician and patient populations allowed us to isolate the effects of physician reimbursement methodology on practice patterns. Compared with fee-for-service, contact capitation reimbursement was associated with significant decreases in cataract extraction rates and costs. The frequency of the cataract extraction surgery, the most common major elective procedure in ophthalmology, was more responsive to physician financial incentives than other ophthalmologic procedures were. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. Barnes Eyecare Network, St Louis, MO USA. Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, Louisville, KY 40292 USA. RP Shrank, W (reprint author), Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Brigham & Womens Hosp, 1620 Tremont St, Boston, MA 02120 USA. EM wshrank@partners.org NR 25 TC 23 Z9 23 U1 1 U2 2 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 DEC PY 2005 VL 123 IS 12 BP 1733 EP 1738 DI 10.1001/archopht.123.12.1733 PG 6 WC Ophthalmology SC Ophthalmology GA 991BS UT WOS:000233787800015 PM 16344447 ER PT J AU Emerick, KS Mehta, A Pilch, BZ Deschler, DG Busse, PM Rocco, JW AF Emerick, KS Mehta, A Pilch, BZ Deschler, DG Busse, PM Rocco, JW TI Pathology quiz case 1 SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID MUCINOUS ADENOCARCINOMA; GLAND C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 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 DEC PY 2005 VL 131 IS 12 BP 1120 EP + DI 10.1001/archotol.131.12.1120 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 991QA UT WOS:000233827300014 PM 16365230 ER PT J AU Truong, LD Krishnan, B Shen, SS AF Truong, LD Krishnan, B Shen, SS TI Intraoperative pathology consultation for kidney and urinary bladder specimens SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID RENAL-CELL CARCINOMA; VONHIPPEL-LINDAU-DISEASE; NEPHRON-SPARING SURGERY; FINE-NEEDLE ASPIRATION; XANTHOGRANULOMATOUS PYELONEPHRITIS; PROSTATIC ADENOCARCINOMA; FROZEN-SECTIONS; ANGIOMYOLIPOMA; TUMORS; ONCOCYTOMA AB Context.-Intraoperative pathology consultation for kidney and urinary bladder specimens is relatively infrequent. Scant literature is devoted to this topic. Objective.-The clinical indications and diagnostic usefulness and pitfalls of intraoperative pathology consultation of kidney and urinary bladder specimens will be reviewed, based on literature and personally encountered cases. Data Sources.-The indications for intraoperative pathology consultation for renal lesions included (1) surgical margins in partial nephrectomy specimens, (2) solid renal mass in unusual clinical or radiologic settings, (3) synchronous renal and extrarenal masses, (4) cystic renal lesions, (5) ureteral surgical margin for transitional cell carcinoma, (6) multiple renal masses, (7) solid mass in a diffusely cystic kidney, and (8) evaluation of renal injury. The indications for urinary bladder included (1) status of the surgical margins, (2) diagnosis of bladder tumor biopsy, (3) diagnosis of extravesical tumors with vesical extension, (4) diagnosis of extravesical mass, including pelvic lymph nodes encountered during cystectomy, and (5) status of bladder neck margin during radical prostatectomy for cancer. The frequent problematic areas for the kidney included misdiagnosis or incorrect classification of cystic tumors or spindle cell tumors, and confusion of clear cell renal cell carcinoma with inflammatory lesions. The problematic areas for urinary bladder included the differential diagnoses of high-grade dysplasia/carcinoma in situ with reactive changes at the ureteral or urethral surgical margins. Conclusions.-Distinctive indications and diagnostic pitfalls are recognized for intraoperative consultation of renal or urinary bladder lesions. Awareness of the pertinent problems should improve diagnostic accuracy and facilitate the proper management of these lesions. C1 Baylor Coll Med, Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP Truong, LD (reprint author), Baylor Coll Med, Methodist Hosp, Dept Pathol, MS 205,6565 Fannin St, Houston, TX 77030 USA. EM ltruong@tmh.tmc.edu NR 58 TC 15 Z9 16 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2005 VL 129 IS 12 BP 1585 EP 1601 PG 17 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 990FT UT WOS:000233729300014 PM 16329731 ER PT J AU Wayne, PM Krebs, DE Macklin, EA Schnyer, R Kaptchuk, TJ Parker, SW Scarborough, DM McGibbon, CA Schaechter, JA Stein, J Stason, WB AF Wayne, PM Krebs, DE Macklin, EA Schnyer, R Kaptchuk, TJ Parker, SW Scarborough, DM McGibbon, CA Schaechter, JA Stein, J Stason, WB TI Acupuncture for upper-extremity rehabilitation in chronic stroke: A randomized sham-controlled study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Physical-Therapy-Association CY JUN 10, 2005 CL Boston, MA SP Amer Phys Therapy Assoc DE acupuncture therapy; cerebrovascular accident; hemiparesis; muscle spasticity; range of motion,articular; rehabilitation ID DESIGNED PLACEBO NEEDLE; FUGL-MEYER ASSESSMENT; QUALITY-OF-LIFE; CLINICAL-TRIALS; ALTERNATIVE MEDICINE; NERVE-STIMULATION; SPASTICITY; CREDIBILITY; RELIABILITY; PERFORMANCE AB Objective: To compare the effects of traditional Chinese acupuncture with sham acupuncture on upper-extremity (UE) function and quality of life (QOL) in patients with chronic hemiparesis from stroke. Design: A prospective, sham-controlled, randomized controlled trial (RCT). Setting: Patients recruited through a hospital stroke rehabilitation program. Participants: Thirty-three subjects who incurred a stroke 0.8 to 24 years previously and had moderate to severe UE functional impairment. Interventions: Active acupuncture tailored to traditional Chinese medicine diagnoses, including electroacupuncture, or sham acupuncture. Up to 20 treatment sessions (mean, 16.9) over a mean of 10.5 weeks. Main Outcome Measures: UE motor function, spasticity, grip strength, range of motion (ROM), activities of daily living, QOL, and mood. All outcomes were measured at baseline and after treatment. Results: Intention-to-treat (ITT) analyses found no statistically significant differences in outcomes between active and sham acupuncture groups. Analyses of protocol-compliant subjects revealed significant improvement in wrist spasticity (P < .01) and both wrist (P < .01) and shoulder (P < .01) ROM in the active acupuncture group, and improvement trends in UE motor function (P = .09) and digit ROM (P = .06). Conclusions: Based on ITT analyses, we conclude that acupuncture does not improve UE function or QOL in patients with chronic stroke symptoms. However, gains in UE function observed in protocol-compliant subjects suggest traditional Chinese acupuncture may help patients with chronic stroke symptoms. These results must be interpreted cautiously because of small sample sizes and multiple, unadjusted, post hoc comparisons. A larger, more definitive RCT using a similar design is feasible and warranted. C1 New England Sch Acupuncture, Dept Res, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ New Brunswick, Inst Biomed Engn, Fredericton, NB, Canada. Spaulding Rehabil Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Wayne, PM (reprint author), New England Sch Acupuncture, Dept Res, 124 Watertown St, Watertown, MA 02472 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 66 TC 49 Z9 51 U1 0 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2005 VL 86 IS 12 BP 2248 EP 2255 DI 10.1016/j.apmr.2005.07.287 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 995VE UT WOS:000234131700003 PM 16344019 ER PT J AU Cully, JA Gfeller, JD Heise, RA Ross, MJ Teal, CR Kunik, ME AF Cully, JA Gfeller, JD Heise, RA Ross, MJ Teal, CR Kunik, ME TI Geriatric depression, medical diagnosis, and functional recovery during acute rehabilitation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cerebrovascular accident; depression; geriatrics; geriatric assessment; rehabilitation ID POSTSTROKE DEPRESSION; INDEPENDENCE MEASURE; SCREENING SCALE; PRIMARY-CARE; LATE-LIFE; STROKE; PREVALENCE; INPATIENTS AB Objective: To examine and compare the prevalence and functional impact of depressive symptoms for older adult stroke and nonstroke rehabilitation inpatients. Design: Case-control study examining functional outcome using a 2 (stroke, nonstroke) by 2 (depression, no depression) design. Setting: Urban hospital rehabilitation unit. Participants: A total of 509 rehabilitation inpatients (age, >= 60y) were included and grouped by diagnosis of stroke (n = 207) and nonstroke (n = 302). Interventions: Not applicable. Main Outcome Measures: Geriatric Depression Scale and FIM instrument. Analysis of covariance procedures examined the impact of depressive symptoms on discharge functional ability controlling for age, sex, admission functional ability, and hospital length of stay. Results: Prevalence of depressive symptoms was similar for stroke (31.8%) and nonstroke (31.5%) and negatively associated with functional ability at discharge for both groups. Overall, the stroke and nonstroke groups did not differ significantly with respect to functional recovery. Conclusions: Depression, and its impact on acute rehabilitation, is significantly related to functional recovery but does not differ in its frequency or impact for stroke patients. Because depressive symptoms do not appear to discriminate across diagnostic groups, routine screening for depression is recommended for all rehabilitation inpatients. C1 Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Vet Affairs HSR&D Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. St Louis Univ, Vet Affairs S Cent Mental Illness Res Educ & Clin, Dept Psychol, St Louis, MO 63103 USA. SSM Rehab, Dept Neuropsychol, St Louis, MO USA. RP Cully, JA (reprint author), 2002 Holcombe 152, Houston, TX 77030 USA. EM jcully@bcm.tmc.edu NR 27 TC 25 Z9 26 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2005 VL 86 IS 12 BP 2256 EP 2260 DI 10.1016/j.apmr.2005.07.292 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 995VE UT WOS:000234131700004 PM 16344020 ER PT J AU Pearlman, JL Cooper, RA Karnawat, J Cooper, R Boninger, ML AF Pearlman, JL Cooper, RA Karnawat, J Cooper, R Boninger, ML TI Evaluation of the safety and durability of low-cost nonprogrammable electric powered wheelchairs SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE reference standards; rehabilitation; safety; wheelchairs ID ANSI/RESNA STANDARDS; MANUAL WHEELCHAIRS; LIFE AB Objective: To evaluate whether a selection of low-cost, nonprogrammable electric-powered wheelchairs (EPWs) meets the American National Standards Institute (ANSI)/Rehabilitation Engineering and Assistive Technology Society of North America (RESNA) Wheelchair Standards requirements. Design: Objective comparison tests of various aspects of power wheelchair design and performance of 4 EPW types. Specimens: Three of each of the following EPWs: Pride Mobility Jet 10 (Pride), Invacare Pronto M50 (Invacare), Electric Mobility Rascal 250PC (Electric Mobility), and the Golden Technologies Alante GP-201-F (Golden). Setting: Rehabilitation engineering research center. Interventions: Not applicable. Main Outcome Measures: Static tipping angle; dynamic tipping score; braking distanced energy consumption, climatic conditionings power and control systems integrity and safety and static, impact, and fatigue life (equivalent cycles). Results: Static tipping angle and dynamic tipping score were significantly different across manufacturers for each tipping direction (range, 6.6 degrees-35.6 degrees). Braking distances were significantly different across manufacturers (range, 7.4-117.3cm). Significant differences among groups were found with analysis of variance (ANOVA). Energy consumption results show that all EPWs can travel over 17km before the battery is expected to be exhausted under idealized conditions (range, 18.2-32.0km). Significant differences among groups were found with ANOVA. All EPWs passed the climatic conditioning tests. Several adverse responses were found during the power and control systems testing, including motors smoking during the stalling condition (Electric Mobility), charger safety issues (Electric Mobility, Invacare), and controller failures (Golden). All EPWs passed static and impact test-ing; 9 of 12 failed fatigue testing (3 Invacare, 3 Golden, 1 Electric Mobility, 2 Pride). Equivalent cycles did not differ statistically across manufacturers (range, 9759-824,628 cycles). Conclusions: Large variability in the results, especially with respect to static tipping, power and control system failures, and fatigue life suggest design improvements must be made to make these low-cost, nonprogrammable EPWs safe and reliable for the consumer. Based on our results, these EPWs do not, in general, meet the ANSI/RESNA Wheelchair Standards requirements. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136; Boninger, Michael/0000-0001-6966-919X NR 16 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2005 VL 86 IS 12 BP 2361 EP 2370 DI 10.1016/j.apmr.2005.07.294 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 995VE UT WOS:000234131700020 PM 16344036 ER PT J AU Jiang, XH Yang, F Tan, HM Liao, D Bryan, RM Randhawa, JK Rumbaut, RE Durante, W Schafer, AI Yang, XF Wang, H AF Jiang, XH Yang, F Tan, HM Liao, D Bryan, RM Randhawa, JK Rumbaut, RE Durante, W Schafer, AI Yang, XF Wang, H TI Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE homocysteine; endothelial function; eNOS; protein kinase C ID CYSTATHIONINE BETA-SYNTHASE; ACCELERATES ATHEROSCLEROSIS; DEFICIENT MICE; MURINE MODEL; L-ARGININE; DYSFUNCTION; HOMOCYSTEINE; MILD; HYPERHOMOCYST(E)INEMIA; INHIBITION AB Objective-A risk factor for cardiovascular disease, hyperhomocystinemia (HHcy), is associated with endothelial dysfunction. In this study, we examined the mechanistic role of HHcy in endothelial dysfunction. Methods and Results-Through the use of 2 functional models, aortic rings and intravital video microscopy of the cremaster, we found that arterial relaxation in response to the endothelium-dependent vessel relaxant, acetylcholine or the nitric oxide synthase ( NOS) activator (A23187), was significantly impaired in cystathionine beta-synthase null (CBS-/-) mice. However, the vascular smooth muscle cell (VSMC) response to the nitric oxide (NO) donor (SNAP) was preserved in CBS-/- mice. In addition, superoxide dismutase and catalase failed to restore endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) activity was significantly reduced in mouse aortic endothelial cells (MAECs) of CBS-/- mice, as well as in Hcy-treated mouse and human aortic endothelial cells (HAECs). Hcy-mediated eNOS inhibition-which was not rescued by adenoviral transduction of superoxide dismutase and glutathione peroxidase, or by tetrahydrobiopterin, sepiapterin, and arginine supplementations in MAEC-was associated with decreased protein expression and increased threonine 495 phosphorylation of eNOS in HAECs. Ultimately, a protein kinase C (PKC) inhibitor, GF109203X (GFX), reversed Hcy-mediated eNOS inactivation and threonine 495 phosphorylation in HAECs. Conclusions-These data suggest that HHcy impairs endothelial function and eNOS activity, primarily through PKC activation. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Wang, H (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, 2002 Holcombe Blvd 109-129, Houston, TX 77030 USA. EM hongw@bcm.tmc.edu FU NHLBI NIH HHS [HL67033, HL36045, HL59976, HL64721, HL74925, HL77288, K02 HL074925, R01 HL036045, R01 HL059976, R01 HL064721, R01 HL067033, R01 HL077288] NR 33 TC 82 Z9 88 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2005 VL 25 IS 12 BP 2515 EP 2521 DI 10.1161/01.ATV.0000189559.87328.e4 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 986PF UT WOS:000233461500015 PM 16210565 ER PT J AU Carter, RH Zhao, H Liu, XM Pelletier, M Chatham, W Kimberly, R Zhou, T AF Carter, RH Zhao, H Liu, XM Pelletier, M Chatham, W Kimberly, R Zhou, T TI Expression and occupancy systemic lupus of BAFF-R on B cells in erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR FAMILY; LYMPHOCYTE STIMULATOR; AUTOIMMUNE-DISEASE; TNF RECEPTOR; MATURATION ANTIGEN; SJOGRENS-SYNDROME; PERIPHERAL-BLOOD; HUMORAL IMMUNITY; MARGINAL ZONE; HIGH-AFFINITY AB Objective. To determine whether receptors for B lymphocyte stimulator (BLyS) are altered on B cells of patients with systemic lupus erythematosus (SLE). Methods. Total available receptors for BLyS were measured by analysis of binding of recombinant soluble BLyS to peripheral blood B cells in 36 SLE patients, 29 healthy controls, and 10 disease controls. Antibodies to the receptors BAFF-R, BCMA, and TACI were used to define expression of the individual BLyS receptors on subsets of B cells in blood, spleen, and tonsils. Two different antibodies to BAFF-R, which were differentially sensitive to BAFF-R occupancy, were used to compare BAFF-R on B cells in an additional 20 healthy subjects and 25 SLE patients. Assays of B cell survival after stimulation in vitro were used to determine the sensitivity of B cells to exogenous BLyS. Results. Total available receptors for BLyS were decreased in patients with SLE, independent of changes of subsets in the blood in these patients. The decrease correlated with changes in disease activity. Although total surface BAFF-R was not significantly different between healthy controls and SLE patients, BAFF-R was occupied in SLE patients. B cells from these patients were less responsive to exogenous BLyS. Conclusion. BAFF-R is consistently occupied on blood B cells in SLE. Occupancy of BAFF-R on blood B cells is likely to contribute to disease mechanisms in SLE and could serve as a biomarker of disease activity. Targeting BLyS as a therapeutic strategy will require overcoming the persistent binding of BLyS to BAFF-R. C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. BiogenIdec, Cambridge, MA USA. RP Carter, RH (reprint author), 409 LHRB,701 S 19th St, Birmingham, AL 35294 USA. EM rcarter@uab.edu NR 48 TC 68 Z9 76 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 3943 EP 3954 DI 10.1002/art.21489 PG 12 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500033 PM 16320342 ER PT J AU Lee, YH Witte, T Momot, T Schmidt, RE Kaufman, KM Harley, JB Sestak, AL AF Lee, YH Witte, T Momot, T Schmidt, RE Kaufman, KM Harley, JB Sestak, AL TI The Mannose-binding lectin gene polymorphisms and systemic lupus erythematosus - Two case-control studies and a meta-analysis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PROTEIN GENE; RHEUMATOID-ARTHRITIS; CLINICAL-TRIALS; INNATE IMMUNITY; ASSOCIATION; MBL; POPULATION; COMPLEMENT; DEFICIENCY; DISEASE AB Objective. Mannose-binding lectin (MBL) enhances opsonization and activates complement. Dysfunctional alleles of MBL have been associated with low plasma concentrations of MBL and increased risk of systemic lupus erythematosus (SLE), but genotyping studies have shown inconsistent results. We performed case-control studies of the MBL polymorphisms in 2 Caucasian cohorts and a meta-analysis incorporating all published results of MBL genotyping in SLE to explore whether the MBL functional variants are associated with SLE. Methods. MBL genotypes at 7 single-nucleotide polymorphisms were sequenced in 96 European American patients with SLE and 96 age-, race-, and sex-matched controls. MBL codons 52, 54, and 57 were genotyped in 285 German patients with SLE and 200 race-matched controls. Allele frequencies of all known variants were tallied for meta-analysis. Results. Although there was a trend toward association with MBL polymorphisms in both patient cohorts evaluated, none of them was significantly associated with SLE on its own. Seventeen comparisons from 15 studies were included in the meta-analysis. Publication bias was excluded by Egger's regression test (P = 0.14). The overall odds ratio for MBL codon 54 variant B was 1.406 (95% confidence interval 1.221-1.608; P < 0.001). Stratification by ethnicity showed significantly increased odds ratios for association of the MBL codon 54B variant with SLE in African, Asian, and Caucasian cohorts. Conclusion. Meta-analysis of all available studies on MBL polymorphisms and SLE shows that MBL variant alleles such as MBL exon 1 codon 54 B, promoter -550 L, and promoter -221 X are SLE risk factors. This association is robust and persists after incorporation of data from our 2 cohorts in which the association failed to reach significance. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, Oklahoma City, OK 73104 USA. Korea Univ, Seoul 136701, South Korea. Hannover Med Sch, Hannover, Germany. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Sestak, AL (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM andrea-sestak@omrf.ouhsc.edu RI Witte, Torsten/B-5783-2016 FU NCRR NIH HHS [RR-020143]; NIAID NIH HHS [AI-24717, AI-31584]; NIAMS NIH HHS [AR-12253, AR-42460, AR-48940, AR-49272]; NIDCR NIH HHS [DE-015223] NR 49 TC 130 Z9 131 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 3966 EP 3974 DI 10.1002/art.21484 PG 9 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500035 PM 16320344 ER PT J AU Pessler, F Dai, L Chen, LX Schumacher, HP AF Pessler, F Dai, L Chen, LX Schumacher, HP TI Expression of calcineurin in synovium. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Sun Yat Sen Univ, Guangzhou, Peoples R China. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4070 EP 4070 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500092 ER PT J AU Jung, SM Schumacher, HR Lee, SH Kim, HC Chen, LX Pessler, F AF Jung, SM Schumacher, HR Lee, SH Kim, HC Chen, LX Pessler, F TI Anti-inflammatory properties of a mixture of traditional oriental medicinal herbs in acute urate crystal imflammation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Kyung Hee Univ, Sch Oreintal Med, Seoul, South Korea. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA USA. Childrens Hosp, Philadelphia, PA USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4072 EP 4072 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500097 ER PT J AU Pessler, F Dai, L Einhorn, E Cron, RQ Schumacher, HR AF Pessler, F Dai, L Einhorn, E Cron, RQ Schumacher, HR TI Expression of nuclear factor of activated T cells (NFAT) transcription factors in the synovial subintima distinguishes RA from OA. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Sun Yat Sen Univ, Guangzhou, Peoples R China. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4073 EP 4073 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500100 ER PT J AU Roh, EY Dykes, PC Kay, J AF Roh, EY Dykes, PC Kay, J TI Use of digital pen and paper technology to collect patient-reported symptom and functional status data improves physician documentation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA USA. Partners Hlth Care, Wellesley, MA USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4074 EP 4074 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500102 ER PT J AU Lainer, DT Park, GS Paulus, HE Khanna, D Keystone, EC Furst, DE AF Lainer, DT Park, GS Paulus, HE Khanna, D Keystone, EC Furst, DE CA Western Constorium Practicing TI Association of regional baseline joint tenderness and joint wwelling with regional functional outcomes in early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VAMC, Los Angeles, CA USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Inst Study Hlth, Cincinnati, OH USA. Univ Toronto, Toronto, ON, Canada. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4096 EP 4096 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500155 ER PT J AU Lainer, DT Park, GS Paulus, HE Khanna, D Keystone, EC Furst, DE AF Lainer, DT Park, GS Paulus, HE Khanna, D Keystone, EC Furst, DE CA Western Constorium Practicing TI Association of baseline tenderness and swelling with 2-year radiographic outcomes of individual joints in early seropositive rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Los Angeles, CA USA. W Los Angeles VAMC, Los Angeles, CA USA. Univ Cincinnati, VAMC, Cincinnati, OH 45221 USA. Inst Study Hlth, Cincinnati, OH USA. Univ Toronto, Toronto, ON, Canada. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4097 EP 4098 PG 2 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500158 ER PT J AU Blais, MA Baity, MR AF Blais, MA Baity, MR TI A comparison of two mental status examinations in an inpatient psychiatric sample SO ASSESSMENT LA English DT Article DE MMSE; folstein; mental status exam; cognitive impairment in psychiatric populations ID 3MS AB This study compares the psychometric properties and clinical use of the Mini-Mental Status Exam (MMSE) and the Modified MMSE (3MS) in patients admitted to an acute medical psychiatric inpatient unit. Internal consistencies were. 56 for the estimated MMSE and. 72 for the 3MS. Regression analyses revealed that the 3MS was a significant predictor of both length of hospital stay (LOS) and the need for additional services postdischarge. Regressions were also used to evaluate the contribution of the four new items contained in the 3MS: Word Generation, Similarities, Second Recall, and Date and Place of Birth. The 3MS was a significant predictor of LOS and the needfor discharge services, whereas the MMSE did not contribute to any regression model. Word Generation was found to be a significant predictor of patients needing posthospital services. Results support prior findings of the 3MSs superiority over the (estimated) MMSE and help to demonstrate the continued importance of cognitive screening in psychiatric samples. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 19 TC 5 Z9 5 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD DEC PY 2005 VL 12 IS 4 BP 455 EP 461 DI 10.1177/1073191105281441 PG 7 WC Psychology, Clinical SC Psychology GA 984AM UT WOS:000233274800009 PM 16244125 ER PT J AU Ireland, H Konstantoulas, CJ Cooper, JA Hawe, E Humphries, SE Mather, H Goodall, AH Hogwood, J Juhan-Vague, I Yudkin, JS di Minno, G Margaglione, M Hamsten, A Miller, GJ Bauer, KA Kim, YT Stearns-Kurosawa, DJ Kurosawa, S AF Ireland, H Konstantoulas, CJ Cooper, JA Hawe, E Humphries, SE Mather, H Goodall, AH Hogwood, J Juhan-Vague, I Yudkin, JS di Minno, G Margaglione, M Hamsten, A Miller, GJ Bauer, KA Kim, YT Stearns-Kurosawa, DJ Kurosawa, S TI EPCR Ser219Gly: Elevated sEPCR, prothrombin F1+2, risk for coronary heart disease, and increased sEPCR shedding in vitro SO ATHEROSCLEROSIS LA English DT Article DE endothelial protein C receptor; thrombin; heart disease ID PROTEIN-C RECEPTOR; THROMBOMODULIN GENE; VENOUS THROMBOSIS; INFLAMMATION; COAGULATION; ACTIVATION; MECHANISMS; PLASMA; VARIANTS; HIFMECH AB We have progressively analysed three studies of coronary heart disease (CHD) for a variant in EPCR (Ser219Gly). Initially, in a prospective study, NPHSII, while no overall CHD-risk was identified in heterozygotes, homozygotes for 219Gly exhibited a three-fold elevated risk (HR 3.3, CI 1.22-8.96). In diabetics within NPHSII, there was a suggestion that 219Gly+ was associated with elevated CHID-risk (HR 1.89, CI 0.39-9.06) although numbers were small. To further assess the effect of the variant in diabetes, a case-control study of MI, HIFMECH, was used, in which previous analysis had defined a group with metabolic syndrome, by factor analysis. A significant CHD-risk interaction was identified between genotype and the 'metabolic syndrome' factor (interaction p = 0.009). To further assess CHD-risk for this variant in type-2 diabetes and to assess the effect of the variant upon thrombin generation and plasma levels of soluble EPCR, a cross-sectional study of type-2 diabetes was used. A significant CHD-risk was identified for European Whites (OR 2.84, Cl 1.38-5.85) and Indian Asians in this study (OR 1.6, Cl 1.00-2.57) and the frequency of 219GIy was two-fold higher in Indian Asians. Soluble EPCR levels were strongly associated with genotype, with homozygotes for 219GIy having four-fold higher levels (p < 0.0001). In vitro studies of EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219GIy EPCR phenotype. Furthermore, in base-line samples from NPHSII and in the diabetic study, a significant increase in prothrombin F1+2 level was observed for 219GIy. The increased CHD-risk and thrombin generation appears to be acting through increased shedding of the Gly allele from the cell surface. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 UCL, Dept Med, London WC1E 6JF, England. Ealing Gen Hosp, Dept Med, London, England. Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. CHU Timoine, Hematol Lab, Marseille, France. UCL, Diabet & Cardiovasc Dis Acad Unit, Dept Med, London, England. Osped Casa Sollievo Sofferenza, IRCCS, San Giovanni Rotodo, Italy. Karolinska Inst, King Gustaf V Res Inst, Stockholm, Sweden. Wolfson Inst Prevent Med, Med Res Council Cardiovasc Grp, London, England. Harvard Univ, Sch Med, Hematol Sect, Va Boston Healthcare Syst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. OMRF, Free Rad Biol & Aging Res, Oklahoma City, OK USA. RP Ireland, H (reprint author), UCL, Dept Med, 5 Univ St, London WC1E 6JF, England. EM h.ireland@ucl.ac.uk RI Yudkin, John/C-1988-2008; Humphries, Stephen/C-5075-2008; OI Stearns-Kurosawa, Deborah/0000-0003-2486-923X; Di Minno, Giovanni/0000-0003-4235-7166; MARGAGLIONE, MAURIZIO/0000-0001-5627-9221 FU NHLBI NIH HHS [HL64787]; NIAID NIH HHS [AI47575] NR 35 TC 43 Z9 45 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 DEC PY 2005 VL 183 IS 2 BP 283 EP 292 DI 10.1016/j.atherosclerosis.2005.02.028 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 989SV UT WOS:000233695000012 PM 15921688 ER PT J AU Hinton, DE Pich, V Safren, SA Pollack, MH McNally, RJ AF Hinton, DE Pich, V Safren, SA Pollack, MH McNally, RJ TI Anxiety sensitivity in traumatized Cambodian refugees: A discriminant function and factor analytic investigation SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Anxiety Sensitivity Index; Cambodian refugees; posttraumatic stress disorder; panic disorder; factor analysis; discriminant function analysis ID POSTTRAUMATIC-STRESS-DISORDER; HIERARCHICAL STRUCTURE; CLINICAL-SAMPLE; PANIC-DISORDER; INDEX; STUDENTS; ATTACKS AB We examined the psychometric properties and factor structure of a Cambodian translation of the Anxiety Sensitivity Index (ASI) and an Augmented ASI (the ASI supplemented with a 9-item addendum that assesses additional Cambodian concerns about anxiety-related sensations). Both the AST and the Augmented AST distinguished among three diagnostic groups: highest score, PTSD with panic disorder (PP group); next, panic disorder without PTSD (P group); and then, other disorders than PTSD or panic disorder (O group). In the discriminant function analysis using the Augmented AST, the best classificatory predictor (PP vs. P vs. O) was an Addendum item ("It scares me when I stand up and feel dizzy"). The principal component analysis (oblimin rotation) of the AST yielded a 3-factor solution (I, Weak Heart Concerns; II, Control Concerns; II, Social Concerns) and of the Augmented ASI, a 4-factor solution (I, Weak Heart Concerns; II, Control Concerns;III, Wind Attack Concerns; IV, Social Concerns). The item clustering within the factor solution of both the AST and Augmented AST illustrates the role of cultural syndromes in generating fear of mental and bodily events. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Arbour Counseling Ctr, SE Asian Clin, Lowell, MA USA. Harvard Univ, Cambridge, MA 02138 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 23 TC 21 Z9 23 U1 2 U2 2 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 DEC PY 2005 VL 43 IS 12 BP 1631 EP 1643 DI 10.1016/j.brat.2005.01.001 PG 13 WC Psychology, Clinical SC Psychology GA 990AS UT WOS:000233716200006 PM 16239155 ER PT J AU Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED AF Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus; diagnosis; staging ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; RISK-FACTORS; PREDICTIVE FACTORS; RECIPIENTS; BLOOD; DONORS; MULTICENTER; MORTALITY; CHILDREN AB This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least I distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy he considered for patients who meet criteria for chronic GVHD of moderate to severe global severity. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, Cincinnati, OH 45229 USA. Univ Minnesota, Minneapolis, MN USA. Natl Canc Inst, NIH, Bethesda, MD USA. Hop St Louis, Paris, France. Univ Florida, Shands Cans Ctr, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. Naval Med Res Ctr, CW Bill Young Dept Def Marrow Donor Recruitment &, Silver Spring, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Filipovich, AH (reprint author), Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, 333 Burnet Ave,MLC 7015, Cincinnati, OH 45229 USA. EM lisa.filipovich@cchmc.org FU Intramural NIH HHS NR 29 TC 1471 Z9 1526 U1 9 U2 35 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2005 VL 11 IS 12 BP 945 EP 956 DI 10.1016/j.bbmt.2005.09.004 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600002 PM 16338616 ER PT J AU Schwake, CJ Eapen, M Lee, SJ Freytes, CO Giralt, SA Navarro, WH Rizzo, FD van Besien, K Loberiza, FR AF Schwake, CJ Eapen, M Lee, SJ Freytes, CO Giralt, SA Navarro, WH Rizzo, FD van Besien, K Loberiza, FR TI Differences in characteristics of US hematopoietic stem cell transplantation centers by proportion of racial or ethnic minorities SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE ethnic minorities; transplantation centers; hematopoietic stem cell transplantation ID STAGE BREAST-CANCER; UNITED-STATES; NONTEACHING HOSPITALS; COLORECTAL-CANCER; HEALTH-CARE; SURVIVAL; RACE; OUTCOMES; LEUKEMIA; SURGERY AB Racial or ethnic minorities with leukemia who receive HLA-identical sibling hematopoietic stem cell transplants (HSCTs) are reported to have worse survival when compared with whites. Characteristics of US HSCT centers according to the proportion of ethnic minorities who undergo transplantation were compared to explore systematic differences among centers; the association with 100-day mortality was evaluated to determine whether center factors may explain the observed discrepant survival among ethnic minorities. One hundred sixteen US transplantation centers that performed HLA-identical sibling transplantations for leukemia were analyzed. We compared physician and health care provider staffing, transplantation unit procedure and resources, and medical center organization according to the volume procedure ratio of ethnic minorities who underwent transplantation and also according to the ratio of Hispanics who underwent transplantation. Centers that performed transplantation in a higher proportion of ethnic minorities were more likely to perform fewer transplantations per year, to have fewer devoted transplant beds, to be in an urban setting, to have a lower physician to patient volume ratio, and to follow up survivors I year after transplantation. Centers that performed transplantation in a higher proportion of Hispanics were more likely to perform fewer transplantations per year and to have fewer devoted transplantation beds, were less likely to perform outpatient transplantations, were more likely to be in an urban setting, and were less likely to have posttransplantation immunization protocols. Observed differences in center factors were not associated with 100-day mortality after adjustment for disease severity. Our results suggest that the inferior survival reported in ethnic minorities after HSCT may not be readily explained by center effects. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Nebraska, Med Ctr, Dept Internal Med, Hematol Oncol Sect, Omaha, NE 68198 USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Hlth Polisy Inst, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Hematol, San Antonio, TX 78285 USA. S Texas Hlth Care Syst, San Antonio, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Hematol, San Francisco, CA 94143 USA. Univ Chicago, Dept Hematol, Chicago, IL 60637 USA. RP Loberiza, FR (reprint author), Univ Nebraska, Med Ctr, Dept Internal Med, Hematol Oncol Sect, 987680 Nebraska Med Ctr, Omaha, NE 68198 USA. EM floberiza@unmc.edu RI van Besien, Koen/G-4221-2012 OI van Besien, Koen/0000-0002-8164-6211 FU AHRQ HHS [5R03 HS13046-02] NR 40 TC 8 Z9 8 U1 1 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2005 VL 11 IS 12 BP 988 EP 998 DI 10.1016/j.bbmt.2005.07.013 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600007 PM 16338621 ER PT J AU von Knoch, F Jaquiery, C Kowalsky, M Schaeren, S Alabre, C Martin, I Rubash, HE Shanbhag, AS AF von Knoch, F Jaquiery, C Kowalsky, M Schaeren, S Alabre, C Martin, I Rubash, HE Shanbhag, AS TI Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells SO BIOMATERIALS LA English DT Article DE alendronate; risedronate; zoledronate; bisphosphonates; human bone marrow stromal cells; bone morphogenetic protein; total joint replacements ID NITROGEN-CONTAINING BISPHOSPHONATES; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; IN-VITRO; WEAR DEBRIS; POSTMENOPAUSAL WOMEN; MEVALONATE PATHWAY; TITANIUM PARTICLES; ZOLEDRONIC ACID; MINERAL DENSITY AB Bisphosphonates are well known potent inhibitors of osteoclast activity and are widely used to treat metabolic bone diseases. Recent evidence from in vitro and in vivo studies indicates that bisphosphonates may additionally promote osteoblastic bone formation. In this study, we evaluated the effects of three FDA-approved and clinically utilized bisphosphonates, on the proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC). BMSC were obtained from patients undergoing primary total hip arthroplasty for end-stage degenerative joint disease. Cells were treated with or without a bisphosphonate (alendronate, risedronate, or zoledronate) and analyzed over 21 days of culture. Cell proliferation was determined by direct cell counting. Osteogenic differentiation of BMSC was assessed with alkaline phosphatase bioassay and gene expression analyses using conventional RT-PCR as well as real-time quantitative RT-PCR. All bisphosphonates tested enhanced the proliferation of BMSC after 7 and 14 days of culture. Steady-state mRNA levels of key genes involved in osteogenic differentiation such as bone morphogenetic protein-2 (BMP-2), bone sialoprotein-II, core-binding factor alpha subunit I (cbfa1) and type I collagen, were generally increased by bisphosphonate treatment in a type- and time-dependent manner. Gene expression levels varied among the different donors. Enhancement of osteogenic differentiation was most pronounced after 14 days of culture, particularly following zoledronate treatment (p < 0.05 for BMP-2). In conclusion, using a clinically relevant in vitro model we have demonstrated that bisphosphonates enhance proliferation of BMSC and initiate osteoblastic differentiation. When administered around joint replacements, bisphosphonates may potentially compensate for the deleterious effects of particulate wear debris at the bone-implant interface, by encouraging increased numbers of cells committed to the osteoblastic phenotype, and thus improve the longevity of joint replacements. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Biomat Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Basel, Dept Surg, Basel, Switzerland. Univ Basel, Dept Res, Basel, Switzerland. RP Shanbhag, AS (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Biomat Lab, Boston, MA 02115 USA. EM shanbhag@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR-47465-02] NR 44 TC 158 Z9 162 U1 1 U2 31 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 DEC PY 2005 VL 26 IS 34 BP 6941 EP 6949 DI 10.1016/j.biomaterials.2005.04.059 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 957CW UT WOS:000231348000016 PM 16009417 ER PT J AU Wang, ML Williamson, JM AF Wang, ML Williamson, JM TI Generalization of the Mantel-Haenszel estimating function for sparse clustered binary data SO BIOMETRICS LA English DT Article DE composite likelihood; correlation; estimating function; Mantel-Haenszel estimator; nuisance; semiparametric; sparse clustered data ID CONDITIONAL LIKELIHOOD; LONGITUDINAL DATA; MODELS; INFERENCE; DESIGNS; FAMILY AB We extend the Mantel-Haenszel estimating function to estimate both the intra-cluster pairwise correlation and the main effects for sparse clustered binary data. We propose both a composite likelihood approach and an estimating function approach for the analysis of such data. The proposed estimators are consistent and asymptotically normally distributed. Simulation results demonstrate that the two approaches are comparable in terms of bias and efficiency; however, the estimating equation approach is computationally simpler. Analysis of the Georgia High Blood Pressure survey is used for illustration. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. RP Wang, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM mwang@jimmy.harvard.edu NR 26 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2005 VL 61 IS 4 BP 973 EP 981 DI 10.1111/j.1541-0420.2005.00362.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 994WP UT WOS:000234062200014 PM 16401270 ER PT J AU Glahn, DC Bearden, CE Caetano, S Fonseca, M Najt, P Hunter, K Pliszka, SR Olvera, RL Soares, JC AF Glahn, DC Bearden, CE Caetano, S Fonseca, M Najt, P Hunter, K Pliszka, SR Olvera, RL Soares, JC TI Declarative memory impairment in pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE cognition; declarative memory; development; juvenile mania; pediatric bipolar disorder ID NEUROCOGNITIVE FUNCTION; PREFRONTAL CORTEX; RATING-SCALE; MANIA; CHILDREN; SCHIZOPHRENIA; ADOLESCENTS; PHENOTYPE; VALIDITY; RELIABILITY AB Objectives: Impaired verbal declarative memory has been proposed as a trait marker for adult bipolar disorder. However, similar impairments in juvenile-onset bipolar disorder have not been yet documented. Here, we assessed declarative memory in a large sample of clinically well-characterized children with bipolar disorder. Methods: Forty-one children and adolescents with bipolar disorder [21 bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar disorder, not otherwise specified (BP-NOS)] and 17 demographically matched healthy participants completed a standardized learning and memory test. Results: BP-I children recalled and recognized significantly fewer words than healthy subjects, whereas children with BP-II and BP-NOS did not differ from controls. However, individuals with BP-NOS made more perseverative errors and intrusions than the other groups. Severity of mood symptomatology was not associated with memory performance in any bipolar subtype. Conclusions: Findings suggest that declarative memory impairments in juvenile BP-I are similar to those seen in the adult form of the illness. These impairments do not appear to be secondary to clinical state; rather, they may reflect trait-related impairments. Distinct performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined phenotype is significantly heterogeneous, and may not be informative for pathogenetic investigations of bipolar disorder. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. RP Glahn, DC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mail Code 7792,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM glahn@uthscsa.edu RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [M01 RR 01346]; NIMH NIH HHS [MH 01736, MH 068662] NR 43 TC 45 Z9 47 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2005 VL 7 IS 6 BP 546 EP 554 DI 10.1111/j.1399-5618.2005.00267.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 991MO UT WOS:000233818300008 PM 16403180 ER PT J AU Frazier, JA Breeze, JL Makris, N Giuliano, AS Herbert, MR Seidman, L Biederman, J Hodge, SM Dieterich, ME Gerstein, ED Kennedy, DN Rauch, SL Cohen, BM Caviness, VS AF Frazier, JA Breeze, JL Makris, N Giuliano, AS Herbert, MR Seidman, L Biederman, J Hodge, SM Dieterich, ME Gerstein, ED Kennedy, DN Rauch, SL Cohen, BM Caviness, VS TI Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar; brain imaging techniques; child psychiatry; mood disorders ID CHILDHOOD-ONSET SCHIZOPHRENIA; VOXEL-BASED MORPHOMETRY; ANATOMICALLY SPECIFIED METHOD; WHITE-MATTER; ADOLESCENT PATIENTS; PREFRONTAL CORTEX; HEALTHY CONTROLS; MOOD DISORDERS; ABNORMALITIES; MRI AB Objective: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence of such deficits in children with BPD. Methods: Thirty-two youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC) (11.2 +/- 3.0 years) had structured and clinical interviews, neurological examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere, and these units were combined into frontal (FL), temporal (TL), parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were examined using univariate linear regression models with alpha = 0.05. Results: Relative to controls, the BPD youth had significantly smaller bilateral PL, and left TL. Analysis of PL and TL gyri showed significantly smaller volume in bilateral postcentral gyrus, and in left superior temporal and fusiform gyri, while the parahippocampal gyri were bilaterally increased in the BPD group. Although the FL overall did not differ between groups, an exploratory analysis showed that the right middle frontal gyrus was also significantly smaller in the BPD group. Conclusions: Children with BPD showed deficits in PL and TL cortical GM. Further analyses of the PL and TL found differences in areas involved in attentional control, facial recognition, and verbal and declarative memory. These cortical deficits may reflect early age of illness onset. C1 Cambridge Hlth Alliance, Dept Psychiat, Child & Adolescent Neuropsychiat Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Frazier, JA (reprint author), Cambridge Hlth Alliance, Dept Psychiat, Child & Adolescent Neuropsychiat Res Program, 10 Presidents Landing, Boston, MA 02115 USA. EM jfrazier@challiance.org RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [K08 MH001573, K08 MH001573-02, K08 MH001573-03, K08 MH001573-04, K08 MH001573-05, K08 MH001573-06, K08 MH01573-01] NR 72 TC 58 Z9 59 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2005 VL 7 IS 6 BP 555 EP 569 DI 10.1111/j.1399-5618.2005.00258.x PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 991MO UT WOS:000233818300009 PM 16403181 ER PT J AU Althoff, RR Faraone, SV Rettew, DC Morley, CP Hudziak, JJ AF Althoff, RR Faraone, SV Rettew, DC Morley, CP Hudziak, JJ TI Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder SO BIPOLAR DISORDERS LA English DT Review DE bipolar affective disorder; child; genetics ID DEFICIT HYPERACTIVITY DISORDER; SEROTONIN TRANSPORTER GENE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SINGLE-NUCLEOTIDE-POLYMORPHISM; EARLY ADOLESCENT BIPOLARITY; MANIC-DEPRESSIVE ILLNESS; PROSPECTIVE FOLLOW-UP; GENOME-WIDE SCAN; EARLY-ONSET; MOOD DISORDERS AB Juvenile bipolar disorder (JBD) has been a subject of significant research and debate. Phenotypic differences between JBD and adult-onset bipolar disorder have led researchers to question whether or not similar neuropathologic mechanisms will be found. While much is known about the genetic and environmental contributions to the adult-onset phenotype, less is known about their contributions to JBD. Here, we review family, twin, adoption, and molecular genetic studies of JBD. Behavioral genetic data suggest both genetic and environmental contributions to JBD, while molecular genetic studies find linkage to age of onset of bipolar disorder to chromosomes 12p, 14q, and 15q. Additionally, changes associated with symptom age of onset have been recently reported in the brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK3-beta) genes. We contend that further progress in discovering the precise genetic and environmental contributions to JBD may depend on advances in phenotypic refinement, an increased appreciation of comorbid conditions, and more investigation of the longitudinal course of the disorder. C1 Univ Vermont, Dept Psychiat, Div Behav Genet, Burlington, VT 05405 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY USA. RP Hudziak, JJ (reprint author), Univ Vermont, Dept Psychiat, Div Behav Genet, Given B229, Burlington, VT 05405 USA. EM james.hudziak@uvm.edu RI Morley, Christopher P/K-1907-2014; OI Morley, Christopher P/0000-0003-0185-7148; Faraone, Stephen/0000-0002-9217-3982 NR 128 TC 44 Z9 44 U1 4 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2005 VL 7 IS 6 BP 598 EP 609 DI 10.1111/j.1399-5618.2005.00268.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 991MO UT WOS:000233818300013 PM 16403185 ER PT J AU Munshi, NC Anderson, KC AF Munshi, NC Anderson, KC TI To transplant or not to transplant? SO BLOOD LA English DT Editorial Material ID HIGH-DOSE THERAPY; MULTIPLE-MYELOMA PATIENTS; CHEMOTHERAPY; TRIAL; SURVIVAL; RESCUE AB In this issue of Blood, Blade and colleagues report that HDT does not improve overall or event-free survival in patients responding to initial chemotherapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 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 DEC 1 PY 2005 VL 106 IS 12 BP 3687 EP 3688 DI 10.1182/blood-2005-09-3673 PG 2 WC Hematology SC Hematology GA 989HB UT WOS:000233662400012 ER PT J AU Lonial, S Waller, EK Richardson, PG Jagannath, S Orlowski, RZ Giver, CR Jaye, DL Francis, D Giusti, S Torre, C Barlogie, B Berenson, JR Singhal, S Schenkein, DP Esseltine, DLW Anderson, J Xiao, H Heffner, LT Anderson, KC AF Lonial, S Waller, EK Richardson, PG Jagannath, S Orlowski, RZ Giver, CR Jaye, DL Francis, D Giusti, S Torre, C Barlogie, B Berenson, JR Singhal, S Schenkein, DP Esseltine, DLW Anderson, J Xiao, H Heffner, LT Anderson, KC CA SUMMIT CREST Investigators TI Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma SO BLOOD LA English DT Article ID SERUM THROMBOPOIETIN LEVELS; BONE-MARROW; ENDOGENOUS THROMBOPOIETIN; MULTICYCLE CHEMOTHERAPY; KAPPA-B; PHASE-2 AB Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m(2) in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production. C1 Emory Univ, Winship Canc Inst, Atlanta, GA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. Arkansas Canc Res Ctr, Transplant Res Ctr, Little Rock, AR USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Lonial, S (reprint author), 1365 Clifton Rd,NE,Bldg C,Room 4004, Atlanta, GA 30322 USA. EM sloni01@emory.edu FU NIDDK NIH HHS [DK60647] NR 26 TC 179 Z9 183 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3777 EP 3784 DI 10.1182/blood-2005-03-1173 PG 8 WC Hematology SC Hematology GA 989HB UT WOS:000233662400024 PM 16099887 ER PT J AU Joanette, Y Caplan, D Nespoulous, JL Whitaker, H AF Joanette, Y Caplan, D Nespoulous, JL Whitaker, H TI Brain and language as a passion Andre Roch Lecours (1936-2005) SO BRAIN AND LANGUAGE LA English DT Biographical-Item C1 Inst Univ Geriat Montreal, Ctr Rech, Montreal, PQ H3W 1W5, Canada. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA USA. Univ Toulouse Le Mirail, Dept Sci Langage, Le Mirail, France. Inst Sci Cerveau Toulouse, Toulouse, France. Lab Jacques Lordat, Toulouse, France. No Michigan Univ, Dept Psychol, Marquette, MI 49855 USA. RP Joanette, Y (reprint author), Inst Univ Geriat Montreal, Ctr Rech, 4565 Chemin Queen Mary, Montreal, PQ H3W 1W5, Canada. EM yves.joanette@umontreal.ca NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD DEC PY 2005 VL 95 IS 3 BP 361 EP 364 DI 10.1016/j.bandl.2005.08.012 PG 4 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 992QO UT WOS:000233899100001 ER PT J AU Zang, YF Jin, Z Weng, XC Zhang, L Zeng, YW Yang, L Wang, YF Seidman, LJ Faraone, SV AF Zang, YF Jin, Z Weng, XC Zhang, L Zeng, YW Yang, L Wang, YF Seidman, LJ Faraone, SV TI Functional MRI in attention-deficit hyperactivity disorder: Evidence for hypofrontality SO BRAIN & DEVELOPMENT LA English DT Article DE attention-deficit hyperactivity disorder; functional magnetic resonance imaging; Stroop effect; hypofrontality; methylphenidate; compensation ID BASAL GANGLIA VOLUMES; MAGNETIC-RESONANCE; DEFICIT/HYPERACTIVITY DISORDER; CEREBELLAR; CHILDREN; METHYLPHENIDATE; ADHD; SCHIZOPHRENIA; RELAXOMETRY; ADOLESCENTS AB Using event-related functional magnetic resonance imaging to study the Stroop, effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional Neurolmaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IQ in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks. (c) 2005 Elsevier B.V. All rights reserved. C1 Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. 306 Hosp, Dept MRI, Beijing 100101, Peoples R China. Chinese Acad Sci, Inst Psychol, Lab Higher Brain Funct, Beijing 100101, Peoples R China. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100864, Peoples R China. RP Wang, YF (reprint author), Peking Univ, Inst Mental Hlth, Huayuanbeilu 51, Beijing 100083, Peoples R China. EM wangyf@bjmu.edu.cn RI ZANG, Yu-Feng/J-1558-2012; OI ZANG, Yu-Feng/0000-0003-1833-8010; Faraone, Stephen/0000-0002-9217-3982 NR 38 TC 94 Z9 104 U1 8 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD DEC PY 2005 VL 27 IS 8 BP 544 EP 550 DI 10.1016/j.braindev.2004.11.009 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 996UA UT WOS:000234199200002 PM 15876503 ER PT J AU Peppercorn, J Partridge, A Burstein, HJ Winer, EP AF Peppercorn, J Partridge, A Burstein, HJ Winer, EP TI Standards for follow-up care of patients with breast cancer SO BREAST LA English DT Article; Proceedings Paper CT 9th International Conference on Primary Therapy of Early Breast Cancer CY JAN 26-29, 2005 CL St Gallen, SWITZERLAND DE breast cancer; therapy; follow-up ID BRCA2 MUTATION CARRIERS; LYMPH-NODE DISSECTION; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; CONTRALATERAL BREAST; CONSERVING THERAPY; AMERICAN SOCIETY; STAGE-I; WOMEN; CARCINOMA AB In the United States alone, over 200,000 women are diagnosed with invasive breast cancer each year, and another 50,000 are diagnosed with ductal carcinoma in situ. The vast majority of these women will survive for five or more years, and the majority will never experience a recurrence of their disease. Followup care is focused on the early identification of new primary cancer and locoregional recurrences. There is no clear evidence that early identification of distant metastases will. lead to an extension in survival, and for this reason routine imaging studies such as CT and PET scans are not recommended. Comprehensive care for breast cancer survivors should also address late complications of treatment and ongoing psychosocial problems that may have arisen as a result of a breast diagnosis and treatment. Although subspecialists often provide follow-up care for breast cancer survivors, randomized trials have demonstrated that generalists can provide such care. As the number of breast cancer survivors continues to increase, guidelines and programs to provide comprehensive, compassionate, and cost-effective follow-up care will become ever more important. (c) 2005 Published by Elsevier Ltd. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Eric_Winer@dfci.harvard.edu NR 56 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2005 VL 14 IS 6 BP 500 EP 508 DI 10.1016/j.breast.2005.09.001 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 989WP UT WOS:000233705000011 PM 16288876 ER PT J AU Bellon, JR Harris, JR AF Bellon, JR Harris, JR TI What extent of radiation therapy is standard? SO BREAST LA English DT Article; Proceedings Paper CT 9th International Conference on Primary Therapy of Early Breast Cancer CY JAN 26-29, 2005 CL St Gallen, SWITZERLAND DE breast cancer; radiation therapy; chemotherapy ID EARLY BREAST-CANCER; RANDOMIZED CLINICAL-TRIAL; SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; CONSERVING SURGERY; STAGE-I; INTRAOPERATIVE RADIOTHERAPY; LOCOREGIONAL RECURRENCE; CONSERVATIVE TREATMENT AB This review will address: (1) 'what are the current indications for radiation therapy (RT), following both mastectomy and breast-conserving surgery?' and (2) 'if RT is indicated, what are the appropriate volumes or 'targets' to be treated?' Given the complexity of these questions, this review wilt focus on selected topics considered of greatest current interest. In addition, this review will primarily focus on results obtained from randomized clinical trials (RCTs). Finally, we acknowledge an American point of view in our discussion. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Sch Med, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Sch Med, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 66 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2005 VL 14 IS 6 BP 532 EP 540 DI 10.1016/j.breast.2005.08.009 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 989WP UT WOS:000233705000016 PM 16236515 ER PT J AU Regan, MM Gelber, RD AF Regan, MM Gelber, RD TI Predicting response to systemic treatments: Learning from the past to plan for the future SO BREAST LA English DT Article; Proceedings Paper CT 9th International Conference on Primary Therapy of Early Breast Cancer CY JAN 26-29, 2005 CL St Gallen, SWITZERLAND DE breast cancer; predictive factors; estrogen receptors; progesterone receptors; adjuvant therapy; chemotherapy; tamoxifen; STEPP ID EARLY BREAST-CANCER; ENDOCRINE RESPONSIVENESS; ADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; DISEASE-FREE; SUBSETS; THERAPY; COMBINATION; TAMOXIFEN; TUMORS AB Therapeutic effects of adjuvant therapies for breast cancer have been assessed "across the board" and implemented using the principle that if a treatment is effective "on average" then it is effective "for all patients." Exploration and improved understanding of the biological basis for predicting response to available adjuvant therapies is essential to enhance patient care. As illustration, we consider the effects of chemotherapy and tamoxifen in two International Breast Cancer Study Group (IBCSG) trials for postmenopausal women. The level of estrogen receptor (ER) expression in the primary tumor is a powerful predictor of response to adjuvant therapy. Absence of ER identifies a chemosensitive cohort for which concurrent tamoxifen significantly blunts the large chemotherapy effect. High levels of ER expression are associated with good results using tamoxifen atone; adding chemotherapy provides little additional benefit. By contrast, adding chemotherapy to tamoxifen provides additional benefit for patients with node-positive disease and tumors expressing intermediate levels of ER. Identification of chemosensitive targets, e.g., absence of PgR, in tumors with intermediate ER expression is required to further tailor, adding chemotherapy within this otherwise endocrine-responsive cohort. Age is not a therapeutic target. Thus, the biological bases for treatment responsiveness must be defined. All findings from clinical trials and meta-analyses should be presented primarily according to steroid hormone receptor status and future studies should be designed as tailored treatment investigations. (c) 2005 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, 44 Binney St, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu NR 19 TC 22 Z9 22 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2005 VL 14 IS 6 BP 582 EP 593 DI 10.1016/j.breast.2005.08.021 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 989WP UT WOS:000233705000023 PM 16199162 ER PT J AU Dutcher, JP Leon, L Manola, J Friedland, DM Roth, B Wilding, G AF Dutcher, JP Leon, L Manola, J Friedland, DM Roth, B Wilding, G TI Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy - E4896, an Eastern Cooperative Oncology Group Study SO CANCER LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol DE renal cell carcinoma (RCC); antiangiogenesis therapy; Phase II study; carboxyamidotriazole ID SUBCUTANEOUS INTERLEUKIN-2; INTERFERON ALPHA-2A; SIGNAL-TRANSDUCTION; DOSE INTERLEUKIN-2; CANCER; TRIAL; THALIDOMIDE; ANGIOGENESIS; INHIBITOR; THERAPY AB BACKGROUND. The current study evaluated the response rate and 6-month time to disease progression of the antiangiogenesis agent carboxyamidotriazole (CAI) in patients with metastatic renal cell carcinoma (RCC). METHODS. Fifty-seven patients with histologically confirmed metastatic RCC that progressed after biologic therapy (interferon or interleukin-2) were enrolled. Four patients were ineligible. CAI was administered orally as a 28-day cycle. Response and time to disease progression were evaluated. RESULTS. Fifteen of 53 eligible patients received > 5 cycles, but 13 patients eventually discontinued treatment because of progressive disease. The majority of toxicities were Grade 1. However, Grade 3/4 toxicities did occur, the majority of which were gastrointestinal in nature. One of 47 patients evaluable achieved a partial response (1.9%) lasting 172 days. Six of 53 patients were alive and disease progression free at 6 months from the start of treatment (11.3%). The median overall survival was 12.5 months. The survival periods in the low-risk, intermediate-risk, and poor-risk groups were 16.2 months, 20.9 months, and 5.8 months, respectively. CONCLUSIONS. Patients in trials of second-line therapy appear to have a better prognosis than previously considered, in part because they are eligible for another clinical trial. CAI was found to have little to no effect on the natural history of progressive RCC. C1 New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY 10466 USA. Eastern Cooperat Oncol Grp Stat Ctr, Dana Farber Canc Inst, Boston, MA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Vanderbilt Univ, Dept Hematol Oncol, Nashville, TN USA. Univ Wisconsin, Ctr Canc, Madison, WI USA. RP Dutcher, JP (reprint author), New York Med Coll, Our Lady Mercy Canc Ctr, 600 E 233rd St, Bronx, NY 10466 USA. EM jpd4401@aol.com FU NCI NIH HHS [CA39229, CA66636, CA49957, CA-23318, CA21076, CA21115] NR 36 TC 14 Z9 16 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 DEC 1 PY 2005 VL 104 IS 11 BP 2392 EP 2399 DI 10.1002/cncr.21473 PG 8 WC Oncology SC Oncology GA 985ZX UT WOS:000233419200012 PM 16222691 ER PT J AU Gandhi, TK Bartel, SB Shulman, LN Verrier, D Burdick, E Cleary, A Rothschild, JM Leape, LL Bates, DW AF Gandhi, TK Bartel, SB Shulman, LN Verrier, D Burdick, E Cleary, A Rothschild, JM Leape, LL Bates, DW TI Medication safety in the ambulatory chemotherapy setting SO CANCER LA English DT Article DE medication error; ambulatory care; patient safety; chemotherapy; computerized physician order entry; oncology ID PHYSICIAN ORDER ENTRY; ADVERSE DRUG EVENTS; ERRORS; PREVENTION AB BACKGROUND. Little is known concerning the safety of the outpatient chemotherapy process. In the Current study, the authors sought to identify medication error and potential adverse drug event (ADE) rates in the outpatient chemotherapy setting. METHODS. A prospective cohort study of two adult and one pediatric outpatient chemotherapy infusion units at one cancer institute was performed, involving the review of orders for patients receiving medication and/or chemotherapy and chart reviews. The adult infusion units used a computerized order entry writing system, whereas the pediatric infusion unit used handwritten orders. Data were collected between March and December 2000. RESULTS. The authors reviewed 10,112 medication orders (8008 adult unit orders and 2104 pediatric unit orders) from 1606 patients (1380 adults and 226 pediatric patients). The medication error rate was 3% (306 of 10, 112 orders). Of these errors, 82% occurring in adults (203 of 249 orders) had the potential for harm and were potential ADEs, compared with 60% of orders occurring in pediatric patients (34 of 57 orders). Among these, approximately one-third were potentially serious. Pharmacists and nurses intercepted 45% of potential ADEs before they reached the patient. Several changes were implemented in the adult and pediatric settings as a result of these findings. CONCLUSIONS. In the current study, the authors found all ambulatory medication error rate of 3%, including 2% of orders with the potential to cause harm. Although these rates are relatively low, there is clearly the potential for serious patient harm. The current study identified strategies for prevention. C1 Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA USA. Dana Farber Canc Inst, Dept Pharm, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA USA. Harvard Sch Publ Hlth, Boston, MA USA. RP Gandhi, TK (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St, Boston, MA 02120 USA. EM tgandhi@partners.org NR 16 TC 68 Z9 72 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2005 VL 104 IS 11 BP 2477 EP 2483 DI 10.1002/cncr.21442 PG 7 WC Oncology SC Oncology GA 985ZX UT WOS:000233419200023 PM 16245353 ER PT J AU Jo, WS Mizukami, Y Duerr, EM Zukerberg, LR Chung, DC AF Jo, WS Mizukami, Y Duerr, EM Zukerberg, LR Chung, DC TI Wnt signaling can repress thrombospondin-1 expression in colonic tumorigenesis SO CANCER BIOLOGY & THERAPY LA English DT Article DE colon cancer; thrombospondin; angiogenesis; Wnt; K-ras ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; C-MYC; RNA INTERFERENCE; ANGIOGENESIS; CELLS; CARCINOMA; FIBROBLASTS; PATHWAY AB The induction of new blood vessels is critical to the pathogenesis of colon cancer, and inhibition of vascular endothelial growth factor (VEGF) has proven to be an effective approach to the treatment of this malignancy. Another potential therapeutic strategy would utilize endogenous anti-angiogenic molecules such as thrombospondin-1 (TSP-1). However, the regulation of TSP-1 expression in colon cancer is poorly understood. Our results demonstrate that TSP-1 is strongly expressed in normal colonic epithelial cells. However, loss of TSP-1 was observed in early colonic adenomas and it became undetectable in invasive colon cancers. Activation of the Wnt signaling pathway in intestinal epithelial cells repressed TSP-1 gene expression, and inhibition of Wnt signaling in colon cancer cells reversed this repression. Although mutant K-ras also inhibited the TSP-1 promoter in intestinal epithelial cells, silencing of mutant K-ras in colon cancer cells with an activated Wnt pathway did not upregulate TSP-1 expression. Collectively, these findings suggest that activation of the Wnt pathway rather than K-ras plays a more important role in the downregulation of TSP-1 observed in colon cancer. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 825,50 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu FU NCI NIH HHS [CA92594] NR 40 TC 9 Z9 9 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2005 VL 4 IS 12 BP 1361 EP 1366 PG 6 WC Oncology SC Oncology GA 022GV UT WOS:000236044400020 PM 16258261 ER PT J AU Stoddard, AM Fagan, P Sorensen, G Hunt, MK Frazier, L Girod, K AF Stoddard, AM Fagan, P Sorensen, G Hunt, MK Frazier, L Girod, K TI Reducing cigarette smoking among working adolescents: Results from the SMART study SO CANCER CAUSES & CONTROL LA English DT Article DE adolescents; randomized trial; smoking; worksite ID PREVENTION PROJECT; HUTCHINSON SMOKING; HEALTH; EDUCATION AB Objective: The SMART Teens Against the Risks of Tobacco Study was designed to test the feasibility and efficacy of tobacco control intervention methods for employed teens. Methods: A randomized controlled pilot study tested the efficacy of a behavioral intervention delivered between September, 1999, and August, 2000. Baseline and final survey data were collected on 560 teens in four intervention and five control stores. Results: Although smoking prevalence decreased and intention to quit increased more among teens in the intervention stores compared to those in the control stores, the differences were not statistically significant. Conclusions: The worksite holds promise as a possible venue for tobacco prevention and cessation interventions for youth although further research is needed to increase the efficacy of interventions for this setting. C1 New England Res Inst, Watertown, MA 02472 USA. NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Rockville, MD USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Stoddard, AM (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM astoddard@neriscience.com FU NINR NIH HHS [R01 NR04748] NR 20 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2005 VL 16 IS 10 BP 1159 EP 1164 DI 10.1007/s10552-005-0353-z PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 979TL UT WOS:000232967600003 PM 16215865 ER PT J AU Kabbarah, O Chin, L AF Kabbarah, O Chin, L TI Revealing the genomic heterogeneity of melanoma SO CANCER CELL LA English DT Editorial Material ID CUTANEOUS MELANOMA; BRAF C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Kabbarah, O (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu NR 9 TC 17 Z9 17 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2005 VL 8 IS 6 BP 439 EP 441 DI 10.1016/j.ccr.2005.11.008 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 996HE UT WOS:000234164200003 PM 16338657 ER PT J AU Agata, N Nogi, H Bamberg, M Milhollen, M Pu, MY Weitman, S Kharbanda, S Kufe, D AF Agata, N Nogi, H Bamberg, M Milhollen, M Pu, MY Weitman, S Kharbanda, S Kufe, D TI The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE NM-3; docetaxel; NSCLC; tumor xenografts; anti-angiogensis ID ISOCOUMARIN AB The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. ILEX Prod Inc, Boston, MA 02215 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA29431, CA98628] NR 8 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2005 VL 56 IS 6 BP 610 EP 614 DI 10.1007/s00280-005-1013-4 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 971HP UT WOS:000232375100008 PM 15947930 ER PT J AU Yu, CL Wang, SF Pan, PC Wu, MT Ho, CK Smith, TJ Li, Y Pothier, LJ Christiani, DC AF Yu, CL Wang, SF Pan, PC Wu, MT Ho, CK Smith, TJ Li, Y Pothier, LJ Christiani, DC CA Kaosiung Brain Tumor Res Grp TI No association between residential exposure to petrochemicals and brain tumor risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID LOUISIANA; MORTALITY; CANCER; OCCUPATION; REFINERY; TAIWAN C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Pulm & Crit Care Unit, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. Natl Changhua Univ Educ, Dept Geog, Changhua, Taiwan. Kaohsiung Med Univ, Sch Publ Hlth, Kaohsiung, Taiwan. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Wu, Ming-Tsang/D-2385-2009; Wu, Ming-Tsang/G-5637-2012 FU NIEHS NIH HHS [ES 09723, ES 00002] NR 12 TC 7 Z9 7 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 DEC PY 2005 VL 14 IS 12 BP 3007 EP 3009 DI 10.1158/1055-9965.EPI-05-0594 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600033 PM 16365027 ER PT J AU Fukuhara, H Ino, Y Kuroda, T Martuza, RL Todo, T AF Fukuhara, H Ino, Y Kuroda, T Martuza, RL Todo, T TI Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system SO CANCER RESEARCH LA English DT Article ID REPLICATION-COMPETENT; ANTITUMOR IMMUNITY; PACKAGING SYSTEM; HELPER-VIRUS; BRAIN-TUMOR; DNA; THERAPY; ICP34.5; MUTANT AB Conditionally replicating herpes simplex virus type I (HSV-1) vectors are promising therapeutic agents for cancer. Certain antitumor functions may be added to oncolytic activities of recombinant HSV-1 vectors by inserting transgenes into the viral genome. Because conventional homologous recombination techniques had required time-consuming processes to create "armed" oncolytic HSV-1 vectors, we established an innovative construction system using bacterial artificial chromosome and two recombinase systems (Cre/loxP and FLPe/FRT). Using G47 Delta, a safe and efficacious oncolytic HSV-1 with triple gene mutations, as the backbone, this system allowed a rapid generation of multiple vectors with desired transgenes inserted in the deleted ICP6 locus. Four oncolytic HSV-1 vectors, expressing murine interleukin 18 (mIL-18), soluble murine B7-1 [B7-1-immunoglobulin (B7-1-Ig)], both, or none, were created simultaneously within 3 months. In vitro, all newly created recombinant vectors exhibited virus yields and cytopathic effects similar to the parental G47 Delta. In two inummocompetent mouse tumor models, TRAMP-C2 prostate cancer and Neuro2a neuroblastoma, the vector expressing both mIL-18 and B7-1-Ig showed a significant enhancement of antitumor efficacy via T-cell-mediated immune responses. The results show that "arming" with multiple transgenes can improve the efficacy of oncolytic HSV-1 vectors. The use of our system may facilitate the development and testing of various armed oncolytic HSV-1 vectors. (Cancer Res 2005; 65(23): 10663-8). C1 Univ Tokyo, Dept Surg, Bunkyo Ku, Tokyo 1138655, Japan. Univ Tokyo, Dept Urol, Tokyo 1138655, Japan. Univ Tokyo, Dept Neurooncol & Mol Therapeut, Tokyo 1138655, Japan. Univ Tokyo, Dept Neurosurg, Tokyo 1138655, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA USA. RP Todo, T (reprint author), Univ Tokyo, Dept Surg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM toudou-nsu@umin.ac.jp OI Kuroda, Toshihiko/0000-0001-6660-8930 FU NCI NIH HHS [R01 CA102139]; NINDS NIH HHS [R01 NS032677] NR 19 TC 57 Z9 60 U1 0 U2 0 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 DEC 1 PY 2005 VL 65 IS 23 BP 10663 EP 10668 DI 10.1158/0008-5472.CAN-05-2534 PG 6 WC Oncology SC Oncology GA 987HE UT WOS:000233508200006 PM 16322208 ER PT J AU Bellovin, DI Bates, RC Muzikansky, A Rimm, DL Mercurio, AM AF Bellovin, DI Bates, RC Muzikansky, A Rimm, DL Mercurio, AM TI Altered localization of p120 catenin during epithelial to mesenchymal transition of colon carcinoma is prognostic for aggressive disease SO CANCER RESEARCH LA English DT Article ID HUMAN COLORECTAL-CANCER; E-CADHERIN; BREAST-CARCINOMA; TUMOR PROGRESSION; P120-CATENIN; ADHESION; GTPASES; RHO; INHIBITION; EXPRESSION AB We examined the expression and localization of p120 catenin (p120ctn) as a consequence of the epithelial to mesenchymal transition (EMT) of highly differentiated colon carcinoma cells (LIM1863 cells). This unique line grows in suspension as spheroids and undergoes an EMT within 24 hours following stimulation with transforming growth factor-beta and tumor necrosis factor-alpha. Although p120ctn expression remains stable during the EMT, its localization shifts from cell-cell junctions to the cytoplasm. Interestingly, a marked decrease in RhoA activation coincident with E-cadherin loss occurs during the EMT and correlates with the formation of a p120ctn/RhoA complex. Use of RNA interference showed that p120ctn reduction results in increased RhoA activity and a significant decrease in the motility of post-EMT cells. To determine the relevance of these findings to colorectal cancer progression, we assessed p120ctn expression by immunohistochemistry in 557 primary tumors. Of note, we observed that 53% of tumors presented cytoplasmic staining for p120ctn, and statistical analysis revealed that this localization is predictive of poor patient outcome. Cytoplasmic p120ctn correlated with later-stage tumors, significantly reduced 5- and 10-year survival times and a greater propensity for metastasis to lymph nodes compared with junctional p120ctn. We also confirmed that altered localization of p120ctn corresponded with loss or cytoplasmic localization of E-cadherin. These alterations in E-cadherin are also associated with a significant reduction in patient survival time and an increase in tumor stage and lymph node metastasis. These data provide a compelling argument for the importance of both p120ctn and the EMT itself in the progression of colorectal carcinoma. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT USA. RP Mercurio, AM (reprint author), Univ Massachusetts, Med Ctr, Dept Canc Biol, LRB-408,364 Plantat St, Worcester, MA 01605 USA. EM arthur.mercurio@umassmed.edu FU NCI NIH HHS [CA107548] NR 26 TC 104 Z9 118 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2005 VL 65 IS 23 BP 10938 EP 10945 DI 10.1158/0008.CAN-05-1947 PG 8 WC Oncology SC Oncology GA 987HE UT WOS:000233508200039 PM 16322241 ER PT J AU Isakoff, SJ Engelman, JA Irie, HY Luo, J Brachmann, SM Pearline, RV Cantley, LC Brugge, JS AF Isakoff, SJ Engelman, JA Irie, HY Luo, J Brachmann, SM Pearline, RV Cantley, LC Brugge, JS TI Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells SO CANCER RESEARCH LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; CHEMOTHERAPY-INDUCED APOPTOSIS; PHOSPHATIDYLINOSITOL 3-KINASE; MULTIDRUG-RESISTANCE; MAMMALIAN TARGET; ACTIVATION LEADS; HIGH-FREQUENCY; GENE; AKT; OVARIAN AB Activation of the phosphoinositide 3-kinase (PI3K) pathway has been implicated in the pathogenesis of a variety of cancers. Recently, mutations in the gene encoding the p110 alpha. catalytic subunit of PI3K (PIK3CA) have been identified in several human cancers. The mutations primarily result in single amino acid substitutions, with >85% of the mutations in either exon 9 or 20. Multiple studies have shown that these mutations are observed in 18% to 40% of breast cancers. However, the phenotypic effects of these PIK3CA mutations have not been examined in breast epithelial cells. Herein, we examine the activity of the two most common variants, E545K and H1047R, in the MCF-10A immortalized breast epithelial cell line. Both variants display higher PI3K activity than wild-type p110 alpha yet remain sensitive to pharmacologic PI3K inhibition. In addition, expression of p110 alpha mutants in mammary epithelial cells induces multiple phenotypic alterations characteristic of breast tumor cells, including anchorage-independent proliferation in soft agar, growth factor-independent proliferation, and protection from anoikis. Expression of these mutant p110 alpha isoforms also confers increased resistance to paclitaxel and induces abnormal mammary acinar morphogenesis in three-dimensional basement membrane cultures. Together, these data support the notion that the cancer-associated mutations in PIK3CA may significantly contribute to breast cancer pathogenesis and represent attractive targets for therapeutic inhibition. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Bldg C,Room 513,240 Longwood Ave, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA089393, 5T32 CA09172-29, 5T32 CA09172-30, CA105134, CA89021, T32 CA009172]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 55 TC 276 Z9 288 U1 5 U2 12 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 DEC 1 PY 2005 VL 65 IS 23 BP 10992 EP 11000 DI 10.1158/0008-5472.CAN-05-2612 PG 9 WC Oncology SC Oncology GA 987HE UT WOS:000233508200046 PM 16322248 ER PT J AU Celik, I Surfucu, O Dietz, C Heymach, JV Force, J Hoschele, I Becker, CM Folkman, J Kisker, O AF Celik, I Surfucu, O Dietz, C Heymach, JV Force, J Hoschele, I Becker, CM Folkman, J Kisker, O TI Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve SO CANCER RESEARCH LA English DT Article ID CIRCULATING ENDOTHELIAL-CELLS; TUMOR-GROWTH; ANGIOGENESIS INHIBITORS; ANTITUMOR-ACTIVITY; PANCREATIC-CANCER; PROGENITOR CELLS; GENE-TRANSFER; ZINC-BINDING; ANGIOSTATIN; INTEGRINS AB We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other allgiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern. C1 Univ Marburg, Dept Gen Surg, Univ Marburg Hosp, D-35043 Marburg, Germany. Charite, Dept Obstet & Gynecol, Berlin, Germany. Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Celik, I (reprint author), Univ Marburg, Inst Theoret Surg, Univ Marburg Hosp, Baldingerstr, D-35043 Marburg, Germany. EM Celik@mailer.uni-marburg.de FU NCI NIH HHS [R01 CA064481-9] NR 49 TC 93 Z9 99 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2005 VL 65 IS 23 BP 11044 EP 11050 DI 10.1158/0008-5472.CAN-05-2617 PG 7 WC Oncology SC Oncology GA 987HE UT WOS:000233508200052 PM 16322254 ER PT J AU Lee, MS Shah, AP Aragon, J Jamali, A Dohad, S Kar, S Makkar, RR AF Lee, MS Shah, AP Aragon, J Jamali, A Dohad, S Kar, S Makkar, RR TI Drug-eluting stenting is superior to bare metal stenting in saphenous vein grafts SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE drug-eluting stent; percutaneous coronary intervention; saphenous vein graft ID ANGIOGRAPHIC FOLLOW-UP; CORONARY-ARTERY; PERCUTANEOUS TREATMENT; REGISTRY EXPERIENCE; BYPASS-SURGERY; INTERVENTION; IMPLANTATION; REOPERATION; PREDICTORS; RESTENOSIS AB This study compared the outcomes of percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) with drug-eluting stents (DES) with bare metal stents (BMS). PCI of degenerated SVG is associated with worse outcomes and high incidence of in-stent restenosis compared with PCI of native coronary arteries. There is a paucity of data on the outcomes of PCI of SVG with DES. Data from 223 consecutive patients who underwent PCI of SVG were imputed into a dedicated clinical database. We assessed the clinical outcomes at a mean follow-up of 9.1 +/- 2.1 months. A total of 139 patients underwent PCI of SVG with DES and 84 patients with BMS. The mean age of the SVG was 7.6 +/- 3.8 years in the DES group and 7.7 +/- 2.8 years in the BMS group (P = 0.38). Procedural success was achieved in all patients except for one patient in the BMS group who underwent emergent coronary artery bypass graft surgery for SVG dissection. There were no other in-hospital cardiac events in both groups. There was one cardiac death in the DES group and three deaths in the BMS group (P = 0.03). When compared to the BMS, PCI of SVG with DES was associated with a lower incidence of myocardial infarction (4.3% vs. 20.2%; P = 0.04) and target vessel revascularization (10.1% vs. 36.9%; P = 0.035). When compared with BMS, PCI of SVG with DES was associated with a lower incidence of death, myocardial infarction, and target vessel revascularization. (c) 2005 Wiley-Liss, Inc. C1 Cedars Sinai Med Ctr, Cardiovasc Intervent Ctr, Sch Med, Los Angeles, CA 90048 USA. W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. RP Makkar, RR (reprint author), Cedars Sinai Med Ctr, Cardiovasc Intervent Ctr, Sch Med, 8631 W 3rd St,Room 415E, Los Angeles, CA 90048 USA. EM raj.makar@cshs.org NR 27 TC 59 Z9 65 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2005 VL 66 IS 4 BP 507 EP 511 DI 10.1002/ccd.20498 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991GJ UT WOS:000233800100009 PM 16270361 ER PT J AU Fukui, K Yang, Q Cao, Y Takahashi, N Hatakeyama, H Wang, HY Wada, J Zhang, YL Marselli, L Nammo, T Yoneda, K Onishi, M Higashiyama, S Matsuzawa, Y Gonzalez, FJ Weir, GC Kasai, H Shimomura, L Miyagawa, J Wollheim, CB Yamagata, K AF Fukui, K Yang, Q Cao, Y Takahashi, N Hatakeyama, H Wang, HY Wada, J Zhang, YL Marselli, L Nammo, T Yoneda, K Onishi, M Higashiyama, S Matsuzawa, Y Gonzalez, FJ Weir, GC Kasai, H Shimomura, L Miyagawa, J Wollheim, CB Yamagata, K TI The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation SO CELL METABOLISM LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; PANCREATIC BETA-CELLS; DIABETES-MELLITUS; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR; MEMBRANE-FUSION; ALPHA-GENE; FACTOR-I; MUTATIONS; SECRETION AB Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1 alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1 alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1 alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca2+ influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis. C1 Osaka Univ, Dept Metab Med, Grad Sch Med, Suita, Osaka 5650871, Japan. Natl Inst Physiol Sci, Dept Cell Physiol, Okazaki, Aichi 4448787, Japan. Grad Univ Adv Studies, Okazaki, Aichi 4448787, Japan. Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan. Univ Geneva, Med Ctr, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland. Okayama Univ, Dept Med & Clin Sci, Grad Sch Med & Dent, Okayama 7008558, Japan. Joslin Diabet Ctr, Boston, MA 02215 USA. Ehime Univ, Div Biochem & Mol Genet, Dept Cellular & Mol Biol, Sch Med, Ehime 7910295, Japan. NCI, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Yamagata, K (reprint author), Osaka Univ, Dept Metab Med, Grad Sch Med, Suita, Osaka 5650871, Japan. EM kazu@imed2.med.osaka-u.ac.jp RI WADA, Jun/B-2023-2011; OI WADA, Jun/0000-0003-1468-5170; Kasai, Haruo/0000-0003-2327-9027 FU NCRR NIH HHS [U4Z RR 16606]; NIDDK NIH HHS [U19DK61251] NR 41 TC 88 Z9 93 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC PY 2005 VL 2 IS 6 BP 373 EP 384 DI 10.1016/j.cmet.2005.11.003 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 992NX UT WOS:000233891900009 PM 16330323 ER PT J AU Lee, BK Smith, TJ Garshick, E Natkin, J Reaser, P Lane, K Lee, HK AF Lee, BK Smith, TJ Garshick, E Natkin, J Reaser, P Lane, K Lee, HK TI Exposure of trucking company workers to particulate matter during the winter SO CHEMOSPHERE LA English DT Article DE diesel; particulate; PM2.5; elemental and organic carbon; exposure ID DIESEL EXHAUST EXPOSURES; RAILROAD WORKERS; AIR-POLLUTION; ELEMENTAL CARBON; PARTICLE CONCENTRATIONS; FINE PARTICLES; LUNG-CANCER; EMISSIONS; INDOOR; MORTALITY AB This study analyzed the workplace area concentrations and the personal exposure concentrations to fine particulate (PM2.5), elemental carbon (EC), and organic carbon (OC) measured during the winter period in trucking companies. The averaged personal exposure concentrations at breathing zones of workers are much greater than those of the microenvironment concentrations. The highest difference between the area (microenvironment) and personal exposure concentrations was in the PM2.5 concentrations followed by the OC concentrations. The area concentrations of PM2.5, EC, and OC at a large terminal were higher than those at a small one. The highest area concentrations of PM2.5, EC, and OC were observed in the shop areas followed by pick-up and delivery (P&D) areas. The area concentrations and personal exposure to PM2.5, EC, and OC in the shop and P&D areas which are highly affected by diesel engine exhaust emissions were much higher than those in the docks which are significantly affected by liquefied petroleum gas (LPG) engine exhaust emissions. The highest EC fraction to the total carbon (EC + OC) concentrations was observed in the shops, while the lowest one was identified in the offices. The personal exposure of the smoking workers to PM2.5 and OC was much higher than that of the non-smoking workers. However, the smoking might not significantly contribute to the personal exposure to EC. There were significant correlations between the PM2.5 and OC concentrations in both the area and personal exposure concentrations. However, significant correlations between the PM2.5 and EC concentrations and between the OC and EC concentrations were not identified. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Ulsan, Dept Civil & Environm Engn, Ulsan 680749, South Korea. Boston Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Pulm & Crit Care Med Sect, Channing Lab,Med Serv,Dept Med,Sch Med,VA Boston, Boston, MA 02115 USA. Univ Massachusetts, Environm Studies PhD Program, Lowell, MA 01854 USA. RP Lee, BK (reprint author), Univ Ulsan, Dept Civil & Environm Engn, Mugeo Dong, Ulsan 680749, South Korea. EM bklee@ulsan.ac.kr FU NCI NIH HHS [R01 CA090792, CA90792] NR 33 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD DEC PY 2005 VL 61 IS 11 BP 1677 EP 1690 DI 10.1016/j.chemosphere.2005.03.091 PG 14 WC Environmental Sciences SC Environmental Sciences & Ecology GA 996RV UT WOS:000234193100015 PM 15913707 ER PT J AU Littler, CM Wehling, CA Fagan, KA Messing, RO Dempsey, EC AF Littler, CM Wehling, CA Fagan, KA Messing, RO Dempsey, EC TI Divergent contractile and structural responses of the murine protein kinase C-epsilon null pulmonary circulation to chronic hypoxia SO CHEST LA English DT Article; Proceedings Paper CT 47th Annual Thomas L Petty Aspen Lung Conference CY JUN 09-12, 2004 CL Given Inst Pathobiol, Aspen, CO HO Given Inst Pathobiol C1 Univ Colorado, Hlth Sci Ctr, Cardiovascular Pulm Res Lab, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Dept Neurol, Emeryville, CA USA. RP Littler, CM (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiovascular Pulm Res Lab, Box B133,4200 E 9th Ave, Denver, CO 80262 USA. EM cassana.littler@uchsc.edu RI Messing, Robert/D-3642-2015 OI Messing, Robert/0000-0002-5345-4431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2005 VL 128 IS 6 SU S BP 620S EP 621S DI 10.1378/chest.128.6_suppl.620S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 999EK UT WOS:000234371400059 PM 16373877 ER PT J AU Kuester, LB Fischman, AJ Fan, CM Halpern, EF Aquino, SL AF Kuester, LB Fischman, AJ Fan, CM Halpern, EF Aquino, SL TI Lipomatous hypertrophy of the interatrial septum - Prevalence and features on fusion 18F fluorodeoxyglucose SO CHEST LA English DT Article DE cardiac neoplasm; 18F fluorodeoxyglucose; image processing,computer-assisted; positron emission tomography; tomography,helical computed ID MASSIVE FATTY DEPOSITS; INTER-ATRIAL SEPTUM; MORPHOLOGIC FEATURES; ADIPOSE-TISSUE; ECHOCARDIOGRAPHY; PET/CT AB Objective: To determine the prevalence of lipomatous hypertrophy of the interatrial septum (LHIS) on CT and its metabolic pattern on 18F fluorodeoxyglucose (FDG)-positron emission tomography (PET). Method and materials: Eight hundred two CT PET scans were reviewed. Patients were included if the interatrial septum was >= 1 cm and excluded if there was evidence of malignancy in the adjacent lung, hilum, or mediastinum. CT scans were fused with PET scans, and the mean standardized uptake value (SUV) was calculated over the LHIS, chest wall (CW) fat, and mediastinal blood pool. CT scans were reviewed for presence of excessive fat in the mediastinum, pericardial, peridiaphragmatic, peiritoneal, and retroperitoneal regions and for the presence of emphysema. Medical records were reviewed for body mass index (BMI) and history of arrhythmia. Results: Twenty-three of 802 patients (2.8%) had LHIS on CT (9 women and 14 men); average age was 75.6 years (range, 58 to 95 years). Average BMI of 17 patients (+/- SD) was 31 +/- 4.9 (range, 22.1 to 39.9). Mean CT values were as follows; thickening of LHIS, 1.47 +/- 0.35 cm (range, 1.07 to 2.25 cm); LHIS, - 79.6 + 24.5 Hounsfield unit (HU) [range, - 11 to - 121 HU]. LHIS was dumbbell shaped in 18 patients. Mean SUVs were as follows: LHIS, 1.84 +/- 0.10 (range, 0.48 to 3.48); CW fat, 0.36 + 0.37 (range, 0.04 to 1.98); blood pool, 1.74 + 0.51 (range, 0.25 to 2.71). The SUV of LHIS was greater than the SUV of CW wall fat in all patients (p < 0.0001). There was significant correlation between SUV and thickness of the LHIS on CT (p < 0.0001, r = 0.883). Those with dumbbell-shaped LHIS (p < 0.003) and presence of emphysema (p < 0.0377) had greater LHIS mean SUV. Conclusion: The SUV of LHIS was greater than the SUV of CW fat in all patients. LHIS with greater thickness or dumbbell shape had greater FDG uptake. These findings on CT and PET are important to recognize in order to avoid false-positive FDG-PET interpretations. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM saquino@partners.org NR 20 TC 23 Z9 24 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2005 VL 128 IS 6 BP 3888 EP 3893 DI 10.1378/chest.128.6.3888 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 997HK UT WOS:000234235900019 PM 16354859 ER PT J AU Dranoff, G AF Dranoff, G TI The therapeutic implications of intratumoral regulatory T cells - Commentary on Wolf et al p. 8326 SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID IMMUNOLOGICALLY MEDIATED REGRESSION; OVARIAN-CANCER; DENDRITIC CELLS; LUNG-CANCER; TUMOR; IMMUNITY; CONSEQUENCE; EXPRESSION; PROMOTION; RESPONSES C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch 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 FU NCI NIH HHS [CA111506, CA092625, CA66996, CA78378] NR 31 TC 23 Z9 24 U1 0 U2 3 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 DEC 1 PY 2005 VL 11 IS 23 BP 8226 EP 8229 DI 10.1158/1078-0432.CCR-05-2035 PG 4 WC Oncology SC Oncology GA 989VF UT WOS:000233701300002 PM 16322278 ER PT J AU Cohen, EEW Kane, MA List, MA Brockstein, BE Mehrotra, B Huo, DZ Mauer, AM Pierce, C Dekker, A Vokes, EE AF Cohen, EEW Kane, MA List, MA Brockstein, BE Mehrotra, B Huo, DZ Mauer, AM Pierce, C Dekker, A Vokes, EE TI Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; LUNG-CANCER; ZD1839 IRESSA; SOLID TUMORS; POLYMORPHISM; MUTATIONS; ERLOTINIB; THERAPY; GENE AB Purpose: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN. Experimental Design: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of Serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy. Results: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively). Conclusions: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome. C1 Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Northwestern Univ, Feinberg Sch Med, Evanston Northwestern Healthcare, Evanston, IL USA. Long Isl Jewish Med Ctr, Div Hematol & Oncol, New Hyde Pk, NY 11042 USA. RP Cohen, EEW (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM ecohen@medicine.bsd.uchicago.edu FU NCI NIH HHS [5P30CA14599-31] NR 28 TC 143 Z9 147 U1 2 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 DEC 1 PY 2005 VL 11 IS 23 BP 8418 EP 8424 DI 10.1158/1078-0432.CCR-05-1247 PG 7 WC Oncology SC Oncology GA 989VF UT WOS:000233701300028 PM 16322304 ER PT J AU Kinlaw, WB Scott, SM Maue, RA Memoli, VA Harris, RD Daniels, GH Porter, DM Belloni, DR Spooner, ET Ernesti, MM Noll, WW AF Kinlaw, WB Scott, SM Maue, RA Memoli, VA Harris, RD Daniels, GH Porter, DM Belloni, DR Spooner, ET Ernesti, MM Noll, WW TI Multiple endocrine neoplasia 2A due to a unique C609S RET mutation presents with pheochromocytoma and reduced penetrance of medullary thyroid carcinoma SO CLINICAL ENDOCRINOLOGY LA English DT Article ID GERM-LINE MUTATIONS; MUTANT RET; PROTOONCOGENE; DISEASE; TYPE-2; HYPERPARATHYROIDISM; ACTIVATION; PHENOTYPE; DIAGNOSIS; FAMILY AB Objective We have identified a large kindred with multiple endocrine neoplasia 2A (MEN 2A) due to a mutation at RET codon 609 that results in a cysteine to serine substitution, a mutation previously identified in only one case in the literature. We characterized the clinical phenotype of the kindred and the biochemical mechanism of this new mutation. Patients and design The index case, a 42-year-old woman, presented with pheochromocytoma. We screened 29 family members for the presence of the mutation. Of the 15 mutation-positive family members, 11 agreed to undergo further evaluation by physical examination, calcium and pentagastrin-stimulated calcitonin levels, measurement of urinary metanephrines, adrenal imaging and serum calcium levels. Biochemical characterization of the mutation was by transient transfection of human neuroblastoma cells and Western blot analysis. Results This kindred demonstrated an inheritance pattern consistent with autosomal dominant pheochromocytoma. Strikingly, no clinically evident case of medullary thyroid cancer (MTC) was observed among mutation-positive family members. Thyroidectomy in six cases revealed C-cell hyperplasia in all and microscopic MTC in two cases. Transfection experiments using human neuroblastoma cells showed that the mutant RET, unlike the wild-type receptor, is constitutively phosphorylated in the absence of ligand, and thus resembles other previously characterized MEN 2A mutations. Conclusions The identification of a new mutation causing a MEN 2A phenotype that features pheochromocytoma and the surprising absence of clinically apparent MTC has significant implications for carriers of this mutation and provides further insights into the genotype-phenotype correlation in MEN 2A. C1 Dartmouth Coll Sch Med, Dept Med, Div Endocrinol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Physiol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Biochem, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Pathol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Radiol, Lebanon, NH 03756 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thyroid Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Kinlaw, WB (reprint author), Dartmouth Coll Sch Med, Dept Med, Div Endocrinol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM william.b.kinlaw@dartmouth.edu NR 30 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2005 VL 63 IS 6 BP 676 EP 682 DI 10.1111/j.1365-2265.2005.02400.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988CN UT WOS:000233569100012 PM 16343103 ER PT J AU Kuhn, M Shah, S Natasha, T Rittling, SR AF Kuhn, Misty Shah, Sarah Natasha, Tajneen Rittling, Susan R. TI A mouse model of breast cancer metastasis to the choroid of the eye SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE breast cancer; choroidal metastases; uveal metastasis; brain metastasis; mouse model ID BONE; MICE; INVOLVEMENT; MELANOMA; GROWTH AB Transformed mouse mammary epithelial cells, r3T, injected into the arterial circulation form bone metastases with high frequency. Here we report that metastases to the choroid of the eye also occur in these mice with a penetrance of at least 50%. The tumors can occupy as much as half the volume of the eye, and pigmented cells become incorporated into and distributed throughout the tumors. Pigmentation is also observed in the brains and optic nerves of mice with choroidal tumors, suggesting that the tumor cells stimulate migration of pigmented cells along the optic nerve into the brain. To our knowledge, this is the first mouse model of breast cancer choroidal metastasis, and should be useful in the study of this disease. C1 Forsyth Inst, Boston, MA 02115 USA. Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. RP Kuhn, M (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM srittling@forsyth.org FU NIDDK NIH HHS [DK67685] NR 20 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD DEC PY 2005 VL 22 IS 8 BP 685 EP 690 DI 10.1007/s10585-006-9012-3 PG 6 WC Oncology SC Oncology GA 075MJ UT WOS:000239888800009 PM 16708307 ER PT J AU Yeung, E Chung, RT AF Yeung, E Chung, RT TI Microarrays and prediction of interferon response in chronic hepatitis C: Not yet ready for prime time SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; ANTIVIRAL THERAPY; VIRUS; INFECTION; RESISTANCE; PROTEINS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Yeung, E (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 19 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2005 VL 3 IS 12 BP 1192 EP 1194 DI 10.1016/S1542-3565(05)00888-8 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 997HN UT WOS:000234236200008 PM 16361043 ER PT J AU Strahilevitz, J Zellermayer, O Vangel, MG Yonath, H Feinberg, MS Rubinstein, E AF Strahilevitz, J Zellermayer, O Vangel, MG Yonath, H Feinberg, MS Rubinstein, E TI Case clustering in infective endocarditis: the role of availability bias SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Editorial Material DE availability bias; clustering; diagnosis; endocarditis; epidemiology; infective endocarditis ID ECHOCARDIOGRAPHY; BACTEREMIA; ERRORS AB Limited data exist regarding the impact of variations in clinical practice and physicians' cognitive bias on the diagnosis of infective endocarditis (IE). As an illustration of these effects, unexpected clustering of IE diagnosis was encountered in a prospectively studied cohort. Transoesophageal echocardiography examinations for suspected IE were performed more frequently following a diagnosis of IE, and were associated with a subsequent cluster of IE cases. The cognitive bias of physicians resulting from a recent case of IE can lead to a transient increase in diagnosing additional cases of IE. C1 Tel Aviv Univ, Sackler Fac Med, Chaim Sheba Med Ctr, Infect Dis Unit, IL-69978 Tel Aviv, Israel. Interdisciplinary Ctr, Arison Sch Business, Herzliyya, Israel. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Inst Heart, IL-69978 Tel Aviv, Israel. RP Rubinstein, E (reprint author), Univ Manitoba, Fac Med, Infect Dis Sect, 543-730 William Ave,501 Basic Sci Bldg, Winnipeg, MB, Canada. EM rubinste@cc.umanitoba.ca NR 21 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD DEC PY 2005 VL 11 IS 12 BP 955 EP 957 DI 10.1111/j.1469-0691.2005.01255.x PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 985WM UT WOS:000233409400001 PM 16307548 ER PT J AU Malchau, H Garellick, G Eisler, T Karrholm, J Herberts, P AF Malchau, H Garellick, G Eisler, T Karrholm, J Herberts, P TI The Swedish Hip Registry: Increasing the sensitivity by patient outcome data SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material ID ARTHROPLASTY REGISTER; RANDOMIZED-TRIAL; CHARNLEY; REPLACEMENT; FRACTURES AB The Swedish Hip Register was initiated in 1979. The mission of the register is to improve the outcome of THA. The hypothesis is that feedback of data stimulates participating clinics to reflect and improve. In addition to revision surgery, patient-based outcome measures and radiographic results are included to improve sensitivity. All patients who have a total hip arthroplasty answer a questionnaire preoperatively and again after 1, 6, and 10 years postoperatively. The questionnaire includes the Charnley classification, EQ-5D and visual analog scales concerning pain and overall satisfaction and is used by 31 of 81 units. Average costs for the procedure ($11,000) are obtained from a national database. The mean gain in the EQ-5D index after I year for 3900 patients was 0.37, giving a low cost of $3000 per quality adjusted life year. Patient satisfaction and pain amelioration generally was high. The national average 7-year survival (revision as end-point), has improved from 93.5% ( +/- 0.15) to 95.8 ( +/- 0.15) between the two periods 1979 to 1991 and 1992 to 2003. National implant registers define the epidemiology of primary and revision surgery. In conjunction with individual subjective patient data and radiography they contribute to development of evidence-based THA surgery. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Univ Gothenburg, Dept Orthopaed, Inst Surg Sci, Sahlgrenska Univ Hosp, Gothenburg, Sweden. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. EM hmalchau@partners.org NR 31 TC 56 Z9 56 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2005 IS 441 BP 19 EP 29 DI 10.1097/01.blo.0000193517.19556.e4 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 991EI UT WOS:000233794700008 ER PT J AU Huddleston, JI Wiley, JW Scott, RD AF Huddleston, JI Wiley, JW Scott, RD TI Zone 4 femoral radiolucent lines in hybrid versus cemented total knee arthroplasties SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TERM FOLLOW-UP; REPLACEMENT; PROSTHESIS; FIXATION; SYSTEM; INTERFACE; MINIMUM; SUCCESS AB Aseptic loosening of the femoral component is an infrequent but important cause of failure in total knee arthroplasties. Inadequate support in the posterior femoral condylar region (radiographic Zone 4) has been associated with loosening. This zone also has been implicated as a site for ingress of wear debris particles leading to osteolysis. We determined the prevalence of Zone 4 radiolucent lines using fluoroscopy to obtain true lateral radiographs in a series of patients who had bilateral simultaneous total knee arthroplasties with a cemented femur on one side and a cementless porous ingrowth femur on the other. We hypothesized that cementless fixation would yield fewer Zone 4 radiolucent lines than cemented fixation. At an average 7.6 +/- 4.4 years followup, 11 of 16 patients (69%) with cemented femoral fixation had Zone 4 radiolucent lines, whereas none of the patients with cementless prostheses had radiolucent lines. Three of 11 radiolucent lines (27%) were progressive. Knee Society. scores were similar for both groups. No femoral components in either group were clinically loose. When excellent initial stability was obtained, cementless femoral fixation yielded fewer Zone 4 radiolucent lines compared with cemented fixation. Level of Evidence: Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Concord Orthopaed PA, Concord, NH USA. Brigham & Womens Hosp, New England Baptist Hosp, Boston, MA 02115 USA. RP Huddleston, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 1124, Boston, MA 02114 USA. EM hutchhuddleston@yahoo.com NR 42 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2005 IS 441 BP 334 EP 339 DI 10.1097/01.blo.0000180452.11048.b8 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 991EI UT WOS:000233794700050 ER PT J AU Fung, HB Doan, TL AF Fung, HB Doan, TL TI Tinidazole: A nitroimidazole antiprotozoal agent SO CLINICAL THERAPEUTICS LA English DT Review DE tinidazole; trichomomasis; glardiasis; intestinal ameblasis; amebic liver abscess ID HELICOBACTER-PYLORI INFECTION; RANITIDINE BISMUTH CITRATE; SINGLE-DOSE TINIDAZOLE; RESISTANT TRICHOMONAS-VAGINALIS; INTESTINAL AMEBIASIS; TRIPLE THERAPY; GARDNERELLA-VAGINALIS; ANAEROBIC INFECTIONS; ERADICATION REGIMENS; ANTIMICROBIAL AGENTS AB Background: Tinidazole, a structural analogue of metronidazole, is an antiprotozoal agent that has been widely used in Europe and developing countries for > 2 decades with established efficacy and acceptable tolerability. It was recently approved by the US Food and Drug Administration for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Objective: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of tinidazole. Methods: Relevant information was identified through a search of MEDLINE (1966-August 2005), Iowa Drug Information Service (1966-August 2005), and International Pharmaceutical Abstracts (1970-August 2005) using the terms tinidazole, Fasigyn, and nitroimidazole. Results: In vitro, tinidazole exhibits activity against pathogenic protozoa (eg, Trichomonas vaginalis, Entamoeba histolytica, Giardia duodenalis), a wide range of clinically significant anaerobic bacteria (eg, Bacteroides fragilis, Clostridium difficile), and the microaerophilic bacterium Helicobacter pylori. In susceptible protozoal and bacterial cells, tinidazole is reduced to cytotoxic intermediates that covalently bind to DNA, causing irreversible damage. In human adults, tinidazole had a bioavailability of 100% and a V-d of 50.7 L, was minimally bound to plasma protein (12%), had a plasma elimination t(1/2) of 12.3 hours, and was eliminated primarily by hepatic metabolism (similar to 63%). Dose adjustment does not appear to be necessary on the basis of race, sex, or renal function. No data were found on the disposition of tinidazole in patients with hepatic insufficiency; therefore, use of tinidazole in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. Clinical cure rates in patients with trichomoniasis, giardiasis, amebiasis, and amebic liver abscess were generally > 90%. In comparative trials, tinidazole was as effective as metronidazole in the treatment of trichomonasis and was significantly more effective than metronidazole in the treatment of giardiasis (P < 0.05) and amebiasis (P < 0.05). The most commonly reported (> 1%) adverse effects included bitter taste, nausea, abdominal discomfort, anorexia, vomiting, and fatigue. The recommended dosage of tinidazole is a single dose of 2 g for trichomoniasis and giardiasis, and 2 g/d for 3 to 5 days for amebiasis. Conclusions: Tinidazole appears to be a promising agent for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Clinical studies are needed to evaluate the use of tinidazole against anaerobic bacteria and H pylori. C1 James J Peters Vet Affairs Med Ctr, Med Surg Patient Care Ctr, Bronx, NY 10468 USA. Long Isl Jewish Med Ctr, Dept Pharm, New Hyde Pk, NY 11042 USA. RP Fung, HB (reprint author), James J Peters Vet Affairs Med Ctr, Med Surg Patient Care Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM horatio.fung@med.va.gov NR 85 TC 52 Z9 57 U1 0 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD DEC PY 2005 VL 27 IS 12 BP 1859 EP 1884 DI 10.1016/j.clinthera.2005.12.012 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 003SP UT WOS:000234702200001 PM 16507373 ER PT J AU Cutler, C Antin, JH AF Cutler, C Antin, JH TI An overview of hematopoletic stem cell transplantation SO CLINICS IN CHEST MEDICINE LA English DT Review ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC MYELOID-LEUKEMIA; HEPATIC VENOOCCLUSIVE DISEASE; IDIOPATHIC PNEUMONIA SYNDROME; IMMUNE RECONSTITUTION; UNRELATED DONORS; RANDOMIZED-TRIAL; CORD BLOOD; AUTOLOGOUS TRANSPLANTATION AB This article is a broad overview of hematopoietic stem cell transplantation, covering topics such as indications for transplantation, types of transplantation procedures, HLA matching of donors and recipients, procurement of stem cells from donors, and outcomes of transplantation. The major complications of transplantation, such as graft-versus-host disease, and the mechanisms of tissue injury after transplantation are discussed, as are the nature of immunologic impairment and reconstitution after transplantation. Finally future directions in stem cell transplantation are discussed. C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binneyb St,D1b30, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149-01A1] NR 52 TC 16 Z9 19 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2005 VL 26 IS 4 BP 517 EP + DI 10.1016/j.ccm.2005.06.016 PG 12 WC Respiratory System SC Respiratory System GA 987RI UT WOS:000233534600002 PM 16263393 ER PT J AU Ison, MG Fishman, JA AF Ison, MG Fishman, JA TI Cytomegalovirus pneumonia in transplant recipients SO CLINICS IN CHEST MEDICINE LA English DT Review ID BONE-MARROW-TRANSPLANTATION; BRONCHOALVEOLAR LAVAGE FLUID; STEM-CELL TRANSPLANTATION; IMMUNOSUPPRESSIVE AGENT LEFLUNOMIDE; LUNG TRANSPLANTATION; SOLID-ORGAN; HEART-LUNG; GANCICLOVIR PROPHYLAXIS; PREEMPTIVE THERAPY; CMV ANTIGENEMIA AB The incidence of cytomegalovirus (CMV) pneumonia has been reduced by routine antiviral prophylaxis in susceptible populations. Many of the complications of this infection are caused by indirect effects of the virus, including acute and chronic graft rejection, graft-versus-host disease, and superinfection by other viruses, bacteria, and fungi. Distinction must be made between viral secretion and invasion. Invasive procedures are often required for the optimal management of such infections. The use of sensitive and quantitative assays have greatly improved the outcomes of CMV infection. C1 Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 118 TC 24 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2005 VL 26 IS 4 BP 691 EP + DI 10.1016/j.ccm.2005.06.013 PG 16 WC Respiratory System SC Respiratory System GA 987RI UT WOS:000233534600015 PM 16263406 ER PT J AU Biederman, J Spencer, TJ Wilens, TE Weisler, RH Read, SC Tulloch, SJ AF Biederman, J Spencer, TJ Wilens, TE Weisler, RH Read, SC Tulloch, SJ CA SLI381 304 Study Grp TI Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; SLI381 ADDERALL XR; DOUBLE-BLIND; CHILDREN; METHYLPHENIDATE; PLACEBO; IMPACT AB Objective: Assess the long-term safety and effectiveness of Mixed amphetamine salts extended release WAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-escalation study of MAS XR in adults (>= 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mg/day for I week, with subsequent titration up to 60 mg/day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-IV). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs. Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (7.2 +/- 13.04 unit points; P <.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity. Conclusion: Treatment with MAS XR 20-60 mg/day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey Ctr Suite 6A, Boston, MA 02114 USA. EM jbiederman@partners.org NR 29 TC 49 Z9 49 U1 6 U2 21 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 DEC PY 2005 VL 10 IS 12 SU 20 BP 16 EP 25 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 999GH UT WOS:000234376400003 PM 16344837 ER PT J AU Mendez, MF Anderson, E Shapira, JS AF Mendez, MF Anderson, E Shapira, JS TI An investigation of moral judgement in frontotemporal dementia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE frontotemporal dementia; neurobehavior; morality; empathy ID FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; ACQUIRED SOCIOPATHY; PREFRONTAL CORTEX; CLINICAL PICTURE; WORK GROUP; DISEASE; DIAGNOSIS; DAMAGE; BASES AB Objective: To investigate the basis of disturbed moral judgment in patients with frontotemporal dementia (FTD). Background: FTD is characterized by difficulty in modulating social behavior. Patients lack social propriety and may perform sociopathic acts. In addition, FTD patients often lack empathy for others. These findings suggest alterations in the nature of morality in patients with FTD. Method: We administered an inventory of moral knowledge and two moral dilemmas to 26 patients with the frontal variant of FTD, 26 patients with Alzheimer disease (AD), and 26 normal control subjects. The FTD patients met Consensus Criteria for FTD and had corroborative frontal abnormalities on functional neuroimaging. The FTD and AD patients were comparably impaired on dementia measures. Results: All these groups showed the retention of knowledge for moral behavior and the ability to make "impersonal" moral judgments. In contrast, the FTD patients were impaired in their ability to make immediate, emotionally based moral judgments compared with the patients with AD and the normal control subjects. Conclusions: These findings are consistent with an attenuation of the automatic emotional identification with others that is part of the innate moral sense. Such a disturbance may result from neurodegenerative disease affecting the ventromedial frontal cortex. C1 VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Hampshire Coll, Amherst, MA 01002 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu NR 37 TC 139 Z9 143 U1 7 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD DEC PY 2005 VL 18 IS 4 BP 193 EP 197 DI 10.1097/01.wnn.0000191292.17964.bb PG 5 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 994VS UT WOS:000234059900002 PM 16340391 ER PT J AU Morissette, SB VanDyke, M AF Morissette, SB VanDyke, M TI Special series - Adapting CBT for recalcitrant populations - Introduction SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Editorial Material ID PSYCHOLOGICAL TREATMENTS; HEALTH AB Although cognitive behavioral treatnients (CBTs) are empirically established for a wide array of psychological disorders, a fair proportion of patients fail to respond, to these treatments. For these reasons, clinicians and researchers continue to modify and adapt CBT for refractory populations. The purpose of this special sect ion is to highlight adaptations of CBTs for disorders that are traditionally more difficult to treat and/or recalcitrant in nature. These articles focus on chronic depression, panic disorder with moderate to severe agoraphobia, obsessive-compulsive disorder, posttraumatic stress disorder related to childhood abuse, and alcohol dependence. A de scription of each treatment is provided in each article, along with relevant clinical case examples illustrating adaptations of the techniques. C1 VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. St Louis Behav Med Inst, St Louis, MO USA. RP Morissette, SB (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM Sandra.Morissette@med.va.gov NR 13 TC 0 Z9 0 U1 2 U2 2 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD WIN PY 2005 VL 12 IS 1 BP 3 EP 5 DI 10.1016/S1077-7229(05)80034-3 PG 3 WC Psychology, Clinical SC Psychology GA 989OC UT WOS:000233682400002 ER PT J AU Morissette, SB Spiegel, DA Heinrichs, N AF Morissette, SB Spiegel, DA Heinrichs, N TI Sensation-focused intensive treatment for panic disorder with moderate to severe agoraphobia SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; ATAQUES-DE-NERVIOS; ALPRAZOLAM DISCONTINUATION; PSYCHIATRIC EPIDEMIOLOGY; FOLLOW-UP; PREVALENCE; EXPOSURE; RELAPSE; IMIPRAMINE; REMISSION AB The current article presents a detailed description of an intensive treatment program for panic disorder with moderate to severe levels of agoraphobia (PDA), called, Sensation-Focased hitensive Treatment (SFIT). Although the efficacy of traditional CBT treatment programs has been well established for the treatment of PDA, patients with moderate to severe levels of agoraphobia generally do worse, and those with residual agoraphobia at the end of treatment are at greater risk for relapse. SFIT is an 8-day treatment program that. directly targets feared physical sensations and. agoraphobic avoidance. SFIT combines techniques used in traditional CBT along with intensive, ungraded, massed exposure. Preliminary data support. the utility and durability of this intensive treatment program for those with moderate to severe levels of agoraphobia. C1 Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA USA. RP Morissette, SB (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Hungtington Ave, Boston, MA 02130 USA. EM Sandra.Morissette@med.va.gov RI Heinrichs, Nina/A-5069-2009 NR 45 TC 7 Z9 7 U1 4 U2 5 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD WIN PY 2005 VL 12 IS 1 BP 17 EP 29 DI 10.1016/S1077-7229(05)80036-7 PG 13 WC Psychology, Clinical SC Psychology GA 989OC UT WOS:000233682400004 ER PT J AU Reilly-Harrington, NA Knauz, RO AF Reilly-Harrington, NA Knauz, RO TI Cognitive-behavioral therapy for rapid cycling bipolar disorder SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID LIFE EVENTS; DEPRESSION; LITHIUM; COMORBIDITY; ILLNESS; SLEEP; MANIA; NONCOMPLIANCE; PROPHYLAXIS; MANAGEMENT AB This article describes the application of cognitive-behavioral therapy (CBT) to the treatment of rapid cycling bipolar disorder. Between 10% and 24% of bipolar patients experience a rapid cycling course, with 4 or more mood episodes occurring per year. Characterized by nonresponse to standard mood-stabilizing medications, rapid cyclers are particularly in need of effective, adjunctive treatments. Adjunctive CBT has been shown to improve medication compliance and reduce relapse rates in patients with bipolar disorder. However no published trials to date have examined the application of CBT to the treatment of rapid cyclers, with only a single case study existing in the literature. We address challenging clinical problems in the treatment of patients with rapid cycling bipolar disorder and include strategies for managing frequent mood fluctuations, medication compliance, steep hygiene, lifestyle regularity, mood elevation, suicidality, and comorbidity. A case example is included to illustrate the treatment approach. C1 Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Reilly-Harrington, NA (reprint author), Massachusetts Gen Hosp, Harvard Bipolar Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM nhreilly@partners.org NR 60 TC 3 Z9 3 U1 0 U2 1 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD WIN PY 2005 VL 12 IS 1 BP 66 EP 75 DI 10.1016/S1077-7229(05)80041-0 PG 10 WC Psychology, Clinical SC Psychology GA 989OC UT WOS:000233682400009 ER PT J AU Hickman, DL Burkhart-Kasch, S Phillips, TJ AF Hickman, DL Burkhart-Kasch, S Phillips, TJ TI The effect of fostering on the genetic expression of locomotor sensitivity to alcohol SO COMPARATIVE MEDICINE LA English DT Article ID MOUSE HEPATITIS-VIRUS; EMBRYO-TRANSFER; NATURAL PATHOGENS; MATERNAL-CARE; MICE; ETHANOL; BEHAVIOR; LINES; REDERIVATION; TRANSMISSION AB Steps were taken to eradicate endemic mouse coronavirus from a colony that was part of a behavioral project characterizing the genetics of alcohol sensitivity. This behavioral study was conducted to determine whether changing the uterine or rearing environment (as is integral to common rederivation methods) would have a significant effect on the expression of the behavioral traits in question. Selected breeding pairs of the affected lines were divided into four treatment groups: 1) transfer of embryos to pseudopregnant B6D2F1 female mice, 2) fostering offspring to B6D2F1 dams, 3) fostering offspring to a different dam of the same line, and 4) offspring raised by the birth dam. Embryo transfers were successful only in one affected line. At approximately 50 days of age, the offspring were tested for locomotor behavior after intraperitoneal. administration of ethanol or normal saline. There were no statistically significant effects of embryo transfer on the ethanol phenotype (ethanol-induced locomotor depression). Fostering significantly reduced the stimulant response to ethanol of only one mouse line selectively bred for high sensitivity to ethanol-induced stimulation, although the stimulant response of the fostered groups was still quite robust. Overall, the results of this study showed that eradication efforts involving fostering of offspring have a modest impact on the stimulant response to ethanol, but there were insufficient data to draw conclusions regarding the use of embryo transfer. C1 Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. Oregon Hlth Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Hickman, DL (reprint author), Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. RI Hickman, Debra/D-3289-2009 FU NIAAA NIH HHS [P60 AA010760] NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD DEC PY 2005 VL 55 IS 6 BP 498 EP 502 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 002CR UT WOS:000234589500002 PM 16422144 ER PT J AU Ulbricht, C Basch, E Szapary, P Hammerness, P Axentsev, S Boon, H Kroll, D Garraway, L Vora, M Woods, J AF Ulbricht, C Basch, E Szapary, P Hammerness, P Axentsev, S Boon, H Kroll, D Garraway, L Vora, M Woods, J CA Nat Stand Res Collaboration TI Guggul for hyperlipidemia: A review by the Natural Standard Research Collaboration SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Review DE guggul; Commifora mukul; high-density lipoprotein ID ANTI-INFLAMMATORY ACTIVITY; COMMIPHORA-MUKUL; GUM GUGGULU; HYPERCHOLESTEROLEMIA; GUGGULSTERONE; CHOLESTEROL; AGENT; ANTAGONIST; RECEPTOR; TRIAL AB Objective: To evaluate the scientific evidence on guggul for hyperlipidemia including expert opinion, folkloric precedent, history, pharmacology, kinetics /dynamics, interactions, adverse effects, toxicology, and dosing. Methods: Electronic searches were conducted in nine databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on language or quality of publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanism of action. Standardized inclusion/exclusion criteria were utilized for selection. Results: Before 2003, most scientific evidence suggested that guggulipid elicits significant reductions in serum total cholesterol, low-density lipoprotein (LDL), and triglycerides, as well as elevations in high-density lipoprotein (HDL) [Kotiyal JP, Bisht DB, Singh DS. Double blind cross-over trial of gum guggulu (Commiphora mukul) Fraction A in hypercholesterolemia. J Res Indian Med Yoga Horn 1979; 14(2):11-6; Kotiyal JP, Singh DS, Bisht DB. Gum guggulu (Commiphora mukul) fraction 'A' in obesity-a double-blind clinical trial. J Res Ayur Siddha 1985;6(1, 3, 4):20-35; Gaur SP, Garg RK, Kar AM, et at. Gugulipid, a new hypolipidaemic agent, in patients of acute ischaemic stroke: effect on clinical outcome, platelet function and serum lipids. Asia Pacif J Pharm 1997;12:65-9; Urizar NL, Liverman AB, Dodds DT, et at. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science 3 May 2002 [Science Express Reports]; Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989;37(5):323-8; Kuppurajan K, Rajagopalan SS, Rao TK, et at. Effect of guggulu (Commiphora mukul-Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26(5):367-73; Gopal K, Saran RK, Nityanand S, et al. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India 1986;34(4):249-51; Agarwal RC, Singh SP, Saran RK, et at. Clinical trial of gugulipid-a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986;84:626-34; Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res 1988;87:356-60; Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 1994;8(4):659-64; Ghorai M, Mandal SC, Pat M, et at. A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res 2000;14(3):200-02]. However, most published studies were small and methodologically flawed. In August 2003, a well-designed trial reported small significant increases in serum LDL levels associated with the use of guggul compared to placebo [Szapary PO, Wolfe ML, Bloedon LT, et at. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290(6):765-72]. No significant changes in total cholesterol, high-density lipoprotein (HDL), or triglycerides were measured. These results are consistent with two prior published case reports [Das Gupta R. Gugulipid: pro-lipaemic effect. J Assoc Physicians India 1990;38(12):346]. Conclusion: The effects of guggulipid in patients with high cholesterol are not clear, with some studies finding cholesterol-lowering effects, and other research suggesting no benefits. At this time, there is not enough scientific evidence to support the use of guggul for any medical condition. Guggul may cause stomach discomfort or allergic rash as well as other serious side effects and interactions. It should be avoided in pregnant or breast-feeding women and in children. Safety of use beyond 4 months has not been well studied. (C) 2005 Elsevier Ltd. All rights reserved. C1 Nat Stand Res Collaborat, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Toronto, Toronto, ON, Canada. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Northeastern Univ, Boston, MA 02115 USA. RP Ulbricht, C (reprint author), Nat Stand Res Collaborat, 1 Broadway,14th Floor, Cambridge, MA 02142 USA. EM info@naturalstandard.com NR 47 TC 49 Z9 52 U1 0 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD DEC PY 2005 VL 13 IS 4 BP 279 EP 290 DI 10.1016/j.ctim.2005.08.003 PG 12 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 998OL UT WOS:000234328400009 PM 16338199 ER PT J AU Todres, ID Catlin, EA Thiel, MM AF Todres, ID Catlin, EA Thiel, MM TI The intensivist in a spiritual care training program adapted for clinicians SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Critical-Care-Medicine CY JAN, 2002 CL San Diego, CA SP Soc Critical Care Med DE spirituality; spiritual distress; religion; critical care; intensivist; clinical pastoral education ID PHYSICIANS; ATTITUDES; MEDICINE; BELIEFS; HEALTH; ISSUES AB Background: Critical illness is a crisis for the total person, not just for the physical body. Patients and their loved ones often reflect on spiritual, religious, and existential questions when seriously ill. Surveys have demonstrated that most patients wish physicians would concern themselves with their patients' spiritual and religious needs, thus indicating that this part of their care has been neglected or avoided. With the well-documented desire of patients to have their caregivers include the patient's spiritual values in their health care, and the well-documented reality that caregivers are often hesitant to do so because of lack of training and comfort in this realm, clinical pastoral education for health care providers fills a significant gap in continuing education for caregivers. Objectives: To report on the first 6 yrs of a unique training program in clinical pastoral education adapted for clinicians and its effect on the experience of the health care worker in the intensive care unit. We describe the didactic and reflective process whereby skills of relating to the ultimate concerns of patients and families are acquired and refined. Design and Setting: Clinical pastoral education designed for clergy was adapted for the health care worker committed to developing skills in the diagnosis and management of spiritual distress. Clinician participants (approximately 10-12) meet weekly for 5 months (400 hrs of supervised clinical pastoral care training). The program is designed to incorporate essential elements of pastoral care training, namely experience, reflection, insight, action, and integration. Results: This accredited program has been in continuous operation training clinicians for the past 6 yrs. Fifty-three clinicians have since graduated from the program. Graduates have incorporated clinical pastoral education training into clinical medical practice, research, and/or further training in clinical pastoral education. Outcomes reported by graduates include the following: Clinical practice became infused with new awareness, sensitivity, and language; graduates learned to relate more meaningfully to patients/families of patients and discover a richer relationship with them; spiritual distress was (newly) recognizable in patients, caregivers, and self. Conclusions: This unique clinical pastoral education program provides the clinician with knowledge, language, and understanding to explore and support spiritual and religious issues confronting critically ill patients and their families. We propose that incorporating spiritual care of the patient and family into clinical practice is an important step in addressing the goal of caring for the whole person. C1 MassGen Hosp Children, Pediat Crit Care Unit, Boston, MA USA. MassGen Hosp Children, Neonatol Unit, Boston, MA USA. Massachusetts Gen Hosp, Chaplaincy Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Todres, ID (reprint author), MassGen Hosp Children, Pediat Crit Care Unit, Boston, MA USA. NR 21 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 BP 2733 EP 2736 DI 10.1097/01.CCM.0000189749.24916.40 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 999XE UT WOS:000234423700002 PM 16352952 ER PT J AU Finnerty, CC Herndon, DN Jeschke, MG Baker, HV Lopez, MC Moldawer, LL Mason, PH Hayden, DL AF Finnerty, CC Herndon, DN Jeschke, MG Baker, HV Lopez, MC Moldawer, LL Mason, PH Hayden, DL TI Genomic changes in pediatric burn patients. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Florida, Gainesville, FL USA. Massachusetts Gen Hosp, Cambridge, MA USA. Injury Program Investigators, 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 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A50 EP A50 DI 10.1097/00003246-200512002-00182 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900182 ER PT J AU Fujimi, S MacConmara, M Lapchak, P Mannick, JA Lederer, JA Maung, AA AF Fujimi, S MacConmara, M Lapchak, P Mannick, JA Lederer, JA Maung, AA TI Enhanced innate immune system function following severe injury increases resistance to intraperitoneal E. coli infection SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 Brigham & Womens Hosp, HMS, Boston, MA 02115 USA. 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 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A141 EP A141 DI 10.1097/00003246-200512002-00499 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900496 ER PT J AU Grecu, L Lecamwasam, H Bittner, E Bigatello, L Qureshi, A Picard, M AF Grecu, L Lecamwasam, H Bittner, E Bigatello, L Qureshi, A Picard, M TI Limited echo exam of critically ill patients by trained intensivists SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 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 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A58 EP A58 DI 10.1097/00003246-200512002-00211 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900210 ER PT J AU Kline, JA Hernandez, J Rose, GA Norton, HJ Camargo, CA AF Kline, JA Hernandez, J Rose, GA Norton, HJ Camargo, CA TI Use of biomarkers to prognose six month outcome of normotensive patients with pulmonary embolism. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 Carolinas Med Ctr, Charlotte, NC 28203 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A54 EP A54 DI 10.1097/00003246-200512002-00196 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900197 ER PT J AU Lee, PS Olsen, JL Bajwa, EK Cotich, KL Shone, R Christiani, DC Stossel, T Waxman, AB AF Lee, PS Olsen, JL Bajwa, EK Cotich, KL Shone, R Christiani, DC Stossel, T Waxman, AB TI Low plasma gelsolin level in sepsis is associated with increased mortality SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A163 EP A163 DI 10.1097/00003246-200512002-00576 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900571 ER PT J AU Zhu, XS Bagchi, A Zhao, HL Duran, CI Hajjar, RJ Chao, W Hellman, J Schmidt, U AF Zhu, XS Bagchi, A Zhao, HL Duran, CI Hajjar, RJ Chao, W Hellman, J Schmidt, U TI MYD88 is indispensable for peptidoglycan-associated lipoprptein (PAL) -induced dysfunction and death in mouse cardiomyocytes. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A15 EP A15 DI 10.1097/00003246-200512002-00057 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900058 ER PT J AU Warren, HS AF Warren, HS TI Toll-like receptors SO CRITICAL CARE MEDICINE LA English DT Article ID INNATE IMMUNITY; RECOGNITION; AGONIST; TLR4; GENE C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI 059010]; NIGMS NIH HHS [R01 GM 59694] NR 18 TC 19 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S BP S457 EP S459 DI 10.1097/01.CCM.0000185504.39347.5D PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 000ZK UT WOS:000234501300018 PM 16340420 ER PT J AU Palevsky, PM Baldwin, I Davenport, A Goldstein, S Paganini, E AF Palevsky, PM Baldwin, I Davenport, A Goldstein, S Paganini, E TI Renal replacement therapy and the kidney: minimizing the impact of renal replacement therapy on recovery of acute renal failure SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE acute renal failure; continuous renal replacement therapy; hemodialysis ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE; ANAPHYLACTOID REACTIONS; REQUIRING DIALYSIS; ROLLER-PUMPS; HEMODIALYSIS; MEMBRANES; INTERMITTENT; TRIAL; BIOCOMPATIBILITY AB Purpose of review Although renal replacement therapy is the mainstay of supportive care in patients with severe acute renal failure, performance can have untoward effects that contribute to the prolongation of renal failure or impede the ultimate recovery of renal function, In this review, we categorize the major complications associated with renal replacement therapy and assess their impact on recovery of renal function. Recent findings The major mechanisms by which renal replacement therapy is postulated to delay renal recovery include treatment-associated hemodynamic instability, vascular catheter-related bacteremia and sepsis, and cytokine activation by bioincompatible membranes. Clinical data regarding the role of dialysis catheter infections in delay of renal recovery are lacking. The data regarding the role of membrane biocompatibility and the modality and dose of renal replacement therapy are limited and conflicting. Summary Clinical recommendations must be limited to the broad admonishment that complications during renal replacement therapy, including hemodynamic instability and catheter-related bacteremia, be minimized by using best clinical practices, while recognizing that the impact of specific practices on recovery of renal function have not been evaluated. The data do not support recommendations regarding utilization of specific membranes or the modality or dose of renal replacement therapy on the basis of their impact on recovery of renal function. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Austin Hosp, Heidelberg, Vic 3084, Australia. Royal Free Hosp, London NW3 2QG, England. Univ Coll Med Sch, London, England. Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Room 7E123 111F-U,Univ Dr Div, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 40 TC 34 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD DEC PY 2005 VL 11 IS 6 BP 548 EP 554 DI 10.1097/01.ccx.0000179936.21895.a3 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 987HC UT WOS:000233508000006 PM 16292058 ER PT J AU Briggs, SM AF Briggs, SM TI Disaster management teams SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE disaster management teams; field triage; incident command system; mass casualty incident ID MASS CASUALTIES; TERRORISM; PREPAREDNESS; ASSOCIATION; THREAT; LEVEL; CARE AB Purpose of review All disasters, regardless of cause, have similar medical and public health consequences. A consistent approach to disasters, based on an understanding of their common features and the response expertise they require, is becoming the accepted practice throughout the world. This strategy is called the mass casualty incident response. The complexity of today's disasters, particularly the threat of terrorism and weapons of mass destruction, has increased the need for multidisciplinary medical specialists as critical assets in disaster response. A review of the current literature emphasizes the expanding role of disaster management teams as an integral part of the mass casualty incident response. Recent findings The incident command system has become the accepted standard for all disaster response. Functional requirements, not titles, determine the organizational hierarchy of the Incident Command System structure. All disaster management teams must adhere to this structure to integrate successfully into the rescue effort. Increasingly, medical specialists are determining how best to incorporate their medical expertise into disaster management teams that meet the functional requirements of the incident command system. Summary Disaster management teams are critical to the mass casualty incident response given the complexity to today's disaster threats. Current disaster planning and response emphasizes the need for an all-hazards approach. Flexibility and mobility are the key assets required of all disaster management teams. Medical providers must respond to both these challenges if they are to be successful disaster team members. C1 Massachusetts Gen Hosp, Int Trauma & Disaster Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Briggs, SM (reprint author), Massachusetts Gen Hosp, Int Trauma & Disaster Inst, 8 Hawthorne Pl,Suite 114, Boston, MA 02114 USA. EM sbriggs@partners.org NR 43 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD DEC PY 2005 VL 11 IS 6 BP 585 EP 589 DI 10.1097/01.ccx.00001186916.92757.ab PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 987HC UT WOS:000233508000012 PM 16292064 ER PT J AU Batchelor, T AF Batchelor, T TI Neuro-oncology update: 2005 SO CURRENT OPINION IN NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Neurol Serv, Boston, MA 02115 USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurol Oncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 1 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 631 EP 631 DI 10.1097/01.wco.0000189873.92362.dc PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800002 PM 16280672 ER PT J AU Plotkin, SR AF Plotkin, SR TI Update on primary central nervous system lymphoma SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE guidelines; neuropsychology; neurotoxicity; recurrent ID PRIMARY-CNS-LYMPHOMA; B-CELL LYMPHOMAS; IMMUNOCOMPETENT PATIENTS; DOSE METHOTREXATE; CHEMOTHERAPY; TEMOZOLOMIDE; RADIATION; RITUXIMAB; SALVAGE; BRAIN AB Purpose of review Primary central nervous system lymphoma is a rare form of extranodal non-Hodgkin's lymphoma that is confined to the central nervous system and eye. Numerous studies examining this disorder have been published in the past 2 years. This review will discuss recent advances in the understanding of the pathology, radiographic appearance, and treatment of this disorder. Recent findings Novel treatment regimens continue to be studied for newly diagnosed and recurrent primary central nervous system lymphoma. As overall survival improves, the burden of late neurotoxicity has become more apparent. Neuropsychological testing of patients treated with chemoradiation shows significant cognitive deficits that can be attributed to whole brain irradiation. Standardization of phase parallel to clinical trials across individual institutions remains an important goal within the oncology community. The International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) has proposed guidelines for the baseline evaluation and response criteria for clinical trials of the disorder. In addition, series of patients with uncommon histological variants of primary central nervous system lymphoma have been published. Summary In 2005, the optimal treatment for primary central nervous system lymphoma remains undefined. Treatment of newly diagnosed disease should include methotrexate-based chemotherapy but the role of irradiation and intrathecal chemotherapy remain unclear. Salvage therapy for progressive or recurrent primary central nervous system lymphoma is an area of active interest but no standard recommendations exist at the present time. Future studies on the biology of recurrent primary central nervous system lymphoma should help to clarify treatment options for these patients. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org NR 40 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 645 EP 653 DI 10.1097/01.wco.0000194142.94546.60 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800005 PM 16280675 ER PT J AU Norden, AD Wen, PY Kesari, S AF Norden, AD Wen, PY Kesari, S TI Brain metastases SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE brain metastases; chemotherapy; stereotactic radiosurgery; surgery; whole brain radiation therapy ID GAMMA-KNIFE RADIOSURGERY; PARTITIONING ANALYSIS RPA; CELL LUNG-CANCER; RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; SURGICAL RESECTION; MOTEXAFIN GADOLINIUM; SINGLE METASTASES AB Purpose of review. Brain metastases occur in 10-30% of cancer patients, and they are associated with a dismal prognosis. Radiation therapy has been the mainstay of treatment for patients without surgically treatable lesions. For patients with good prognostic factors and a single metastasis, surgical resection is recommended. The management of patients with multiple metastases, poor prognostic factors, or unresectable lesions is, however, controversial. Recently published data will be reviewed. Recent findings. Radiation therapy has been shown to substantially reduce the risk of local recurrence after surgical resection of brain metastases, although this does not translate into improved survival. Recently, stereotactic radiosurgery has emerged as an increasingly important alternative to surgery that appears to be associated with less morbidity and similar outcomes. Other potentially promising therapies under investigation include interstitial brachytherapy, new chemotherapeutic agents that cross the blood-brain barrier, and targeted molecular agents. Summary. Patients with brain metastases are now eligible for a number of treatment options that are increasingly likely to improve outcomes. Randomized, prospective trials are necessary to better define the utility of radiosurgery versus surgery in the management of patients with brain metastases. Future investigations should address quality of life and neurocognitive outcomes, in addition to traditional outcome measures such as recurrence and survival rates. The potentially substantial role for chemotherapeutics that cross the blood-brain barrier and for novel targeted molecular agents is now being elucidated. C1 Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Partners Neurol, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Kesari, S (reprint author), Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 57 TC 48 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 654 EP 661 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800006 PM 16280676 ER PT J AU Byrne, TN AF Byrne, TN TI Cognitive sequelae of brain tumor treatment SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE cranial irradiation; neurocognitive; neurogenesis; primary CNS lymphoma ID PRIMARY CNS LYMPHOMA; SYSTEM RADIATION-INJURY; RAT DENTATE GYRUS; QUALITY-OF-LIFE; HIPPOCAMPAL NEUROGENESIS; THERAPEUTIC IRRADIATION; ADULT NEUROGENESIS; ADJUVANT CHEMOTHERAPY; CRANIAL IRRADIATION; PITUITARY-TUMORS AB Purpose of review. The neurocognitive sequelae of anticancer treatment have received increasing attention especially among individuals with low-grade gliomas, primary central nervous system lymphoma and those undergoing prophylactic cranial irradiation for systemic malignancies. These groups are especially vulnerable because they often experience extended survival during which neurocognitive complications of therapy may cause more impairment than the tumor itself. The purpose of this review is to highlight recent clinical-reports of neurocognitive sequelae among patients without significant central nervous system tumor burden and to describe the experimental studies which may explain the pathogenesis of the disorder. Recent findings. The neurocognitive deficits among survivors of primary central nervous system lymphoma without residual tumor and pituitary tumors were reported recently. Both provide an opportunity to distinguish the effects of treatment from the effects of tumor. Moreover, animal studies demonstrate the negative consequences of radiation on hippocampal neurogenesis, learning and memory. The mechanism of impaired neurogenesis may be due to inflammation, which can be aborted with restoration of neurogenesis through the administration of non-steroidal anti-inflammatory agents. Summary. If inhibition of neurogenesis is the basis of neurocognitive sequelae from irradiation and non-steroidal anti-inflammatory agents can restore neurogenesis then a clinical trial may be worthwhile to confirm this benefit in humans. C1 Massachusetts Gen Hosp, Dept Neurol & Hlth Sci Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. MIT, Dept Brain & Cognitiv Sci, Cambridge, MA 02139 USA. RP Byrne, TN (reprint author), 111 Mem Dr, Cambridge, MA 02142 USA. EM tnbyrne@MIT.EDU NR 45 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 662 EP 666 DI 10.1097/01.wco.0000191511.52745.99 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800007 PM 16280677 ER PT J AU Wilck, M Fishman, JA AF Wilck, M Fishman, JA TI The challenges of infection in transplantation: donor-derived infections SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE Chagas' Disease; donor-derived infection; lymphocytic choriomeningitis virus; microbiology; molecular; diagnostics; public health; rabies virus; transplantation; Toxoplasmosis ID WEST-NILE-VIRUS; ORTHOTOPIC LIVER-TRANSPLANTATION; RENAL-TRANSPLANT; MYCOBACTERIUM-TUBERCULOSIS; DISSEMINATED TOXOPLASMOSIS; CARDIAC TRANSPLANTATION; ORGAN-TRANSPLANTATION; STRONGYLOIDES-STERCORALIS; KIDNEY-TRANSPLANT; CADAVER DONOR AB Purpose of review Donor-derived infection is well described in solid organ transplantation. Despite the low incidence of such transmission, the organism burden and morbidity of these infections is amplified in the immunocompromised host. In addition, improvements in microbiologic diagnostic tools have increased the recognition of transmission of infection with allografts that would previously have gone undiagnosed. Recent findings The transmission of potential pathogens with tissue allografts includes common viruses such as cytomegalovirus, Epstein-Barr virus and, before the availability of routine screening, hepatitis B and C infections. Other infections, including bacterial or fungal colonization of donor tissues, or latent tuberculosis or toxoplasmosis have been activated in the transplant recipient. However, recent clusters of cases of rapidly fatal donor-derived viral infections have been identified. These have included infections in multiple recipients of organs from single donors due to rabies, lymphocytic choriomeningitis virus, and West Nile virus. Summary Investigation of donor-derived infections requires suspicion on the part of caregivers, utilization of newer diagnostic tools, and coordination of epidemiologic investigations between medical centers and public health authorities. C1 Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wilck, M (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. NR 50 TC 15 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2005 VL 10 IS 4 BP 301 EP 306 DI 10.1097/01.mot.0000183245.66967.b3 PG 6 WC Transplantation SC Transplantation GA 989NQ UT WOS:000233681200009 ER PT J AU Ip, WKE Charriere, G Cho, JH Ezekowitz, RAB AF Ip, WKE Charriere, G Cho, JH Ezekowitz, RAB TI Receptors and signaling in the innate immune system SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE innate immunity; Nucleoticle Oligomerization Domain containing proteins (NODs); toll-like receptors ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; INTERFERON-ALPHA INDUCTION; PROTEIN-KINASE PKR; C-TYPE LECTINS; MURAMYL DIPEPTIDE; DENDRITIC CELLS; PATHOGEN RECOGNITION; DIAMINOPIMELIC ACID; BETA-GLUCANS AB Purpose of review In this review, we highlight the current conceptual framework for innate immunity. Recent findings We highlight the interactions of pattern recognition receptors, including Toll-like receptors, non-Toll-like membrane-bound pattern recognition receptors, and intracellular sensors neuronal apoptosis inhibitory protein, CIITA, HET-E, and TP1-leucine-rich repeat (NLRs). Toll-like receptors recognize pathogen-associated molecular patterns and activate signaling pathways that induce the expression of immune and proinflammatory genes. Toll-like receptors use overlapping signaling pathways that largely depend on intracellular adaptor molecules. Recent evidence suggests that non-Toll-like membrane-bound pattern recognition receptors such as dectin-1, CD36, and CD14 collaborate with Toll-like receptors in pathogen-associated molecular pattern recognition or use Toll-like receptors as signaling partners. NLRs, whose function is to detect intracellular pathogen-associated molecular patterns, also share the signaling pathways used by some Toll-like receptors, suggesting cooperation and synergy between NLRs and Toll-like receptors. Summary The integration of signals generated from Toll-like receptors and other non-Toll-like receptors might instruct the nature and outcome of the immune response to a particular pathogen. This has implications for inflammatory diseases and host defense, because understanding these precise interactions presents novel targets for specific therapeutics. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, 55 Fruit St,GRJ 1402, Boston, MA 02114 USA. EM ezekowitz.alan@mgh.harvard.edu RI Ip, Eddie/C-3042-2012; Charriere, Guillaume/O-8317-2014 OI Charriere, Guillaume/0000-0002-4796-1488 NR 74 TC 0 Z9 0 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2005 VL 10 IS 4 BP 326 EP 333 DI 10.1097/01.mot.0000186198.62727.4b PG 8 WC Transplantation SC Transplantation GA 989NQ UT WOS:000233681200013 ER PT J AU Arango, NA Szotek, PP Manganaro, TF Oliva, E Donahoe, PK Teixeira, J AF Arango, NA Szotek, PP Manganaro, TF Oliva, E Donahoe, PK Teixeira, J TI Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium SO DEVELOPMENTAL BIOLOGY LA English DT Article DE uterus; myometrium; mullerian duct; mesenchyme; beta-catenin; adipogenesis; myogenesis ID MULLERIAN-INHIBITING SUBSTANCE; FEMALE REPRODUCTIVE-TRACT; SEXUAL DEVELOPMENT; EXPRESSION; GENE; HORMONE; MAMMALS; WNT-7A AB Precise cell fate decisions during differentiation of uterine tissues from the embryonic Mullerian duct are critical for normal fertility. Wnt-7a, a member of the Writ family of secreted signaling molecules that can signal through a canonical beta-catenin pathway, is necessary for the correct differentiation of both anterior/posterior and radial axes of the uterus. In order to investigate the role of beta-catenin directly in mouse uterine development, we have generated mice that are deficient in beta-catenin expression in the embryonic Mullerian duct. We have found that conditional deletion of beta-catenin in the Mullerian duct mesenchyme before postnatal differentiation of the uterine layers results in a phenotype that is distinct from the phenotype observed by deletion of Wnt-7a. Shortly after birth, the uteri of the conditional mutants appear smaller and less organized. The uteri of adult conditional beta-catenin mutants are grossly deficient in smooth muscle of the myometrium, which has been replaced by adipose, a phenotype resembling human lipoleiomyoma. We also show that the adipocytes in the uteri of mice conditionally deleted for beta-catenin are derived from Mullerian inhibiting substance type II receptor-expressing cells suggesting that they share a common origin with the uterine smooth muscle cells. These results describe the first molecular evidence linking disruption of beta-catenin expression in mesenchymal cells with a switch from myogenesis to adipogenesis in vivo. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, CPZN6202,185 Cambridge St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NICHD NIH HHS [F32HD43539, R01HD32112, U54 HD28138] NR 25 TC 113 Z9 122 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2005 VL 288 IS 1 BP 276 EP 283 DI 10.1016/j.ydbio.2005.09.045 PG 8 WC Developmental Biology SC Developmental Biology GA 995BM UT WOS:000234074900020 PM 16256976 ER PT J AU Levy, V Lindon, C Harfe, BD Morgan, BA AF Levy, V Lindon, C Harfe, BD Morgan, BA TI Distinct stem cell populations regenerate the follicle and interfollicular epidermis SO DEVELOPMENTAL CELL LA English DT Article ID LABEL-RETAINING CELLS; HAIR-FOLLICLES; BULGE; SKIN; HEDGEHOG; NICHE; MORPHOGENESIS; EXPRESSION; RENEWAL; REGION AB The regeneration of the skin and its appendages is thought to occur by the regulated activation of a dedicated stem cell population. A population of cells in the bulge region of the hair follicle has been identified as the putative stem cell of both the follicle and the inter-follicular epidermis. While this assertion is supported by a variety of surrogate assays, there has been no direct confirmation of the normal contribution of these cells to the regeneration of structures other than the cycling portion of the hair follicle. Here, we report lineage analysis revealing that the follicular epithelium is derived from cells in the epidermal placode that express Sonic hedgehog. This analysis also demonstrates that the stem cells resident in the follicular bulge that regenerate the follicle are neither the stem cells of the epidermis nor the source of the stem cells of the epidermis in the absence of trauma. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu NR 25 TC 250 Z9 257 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2005 VL 9 IS 6 BP 855 EP 861 DI 10.1016/j.devcel.2005.11.003 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 993MV UT WOS:000233959100016 PM 16326396 ER PT J AU Bruder, D Westendorf, AM Hansen, W Prettin, S Gruber, AD Qian, YJ von Boehmer, H Mahnke, K Buer, J AF Bruder, D Westendorf, AM Hansen, W Prettin, S Gruber, AD Qian, YJ von Boehmer, H Mahnke, K Buer, J TI On the edge of Autoimmunity - T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes SO DIABETES LA English DT Article ID IN-VIVO; NOD MICE; TRANSGENIC MODEL; THYMIC SELECTION; ANTIGEN; TOLERANCE; EXPRESSION; RECEPTOR; INTERLEUKIN-10; MELLITUS AB Targeting of antigens to immature dendritic cells has been shown to result in antigen-specific T-cell tolerance in vivo. In the INS-HA/TCR-HA transgenic mouse model for type 1 diabetes, we tested the potential of the dendritic cell-specific monoclonal antibody DEC-205 conjugated to the hemagglutinin (HA) antigen (DEC-HA) to prevent disease onset. Whereas untreated INS-HA/TCR-RA mice all develop insulitis, and similar to 40% of these mice become diabetic, repeated injection of newborn mice with DEC-HA protected almost all mice from disease development. Histological examination of the pancreata revealed significant reduction of peri-islet infiltrations in DEC-HA-treated mice, and the islet structure remained intact. Moreover, RA-specific CD4(+) T-cells from anti-DEC-HA-treated INS-HA/TCR-HA mice exhibited increased expression of Foxp3, cytotoxic T-lymphocyte-associated antigen-4, and the immunosuppressive cytokines interleukin-10 and transforming growth factor-P. The findings indicate that targeting of the HA antigen to immature dendritic cells in vivo leads to a relative increase of antigen-specific Foxp3(+) regulatory T-cells that suppress the development of type 1 diabetes. Our results provide a basis for the development of novel strategies focusing on prevention rather than treatment of autoimmune diseases. C1 German Res Ctr Biotechnol, Dept Mucosal Immun, D-38124 Braunschweig, Germany. Free Univ Berlin, Dept Vet Pathol, D-1000 Berlin, Germany. Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hannover Med Sch, Inst Med Microbiol, D-3000 Hannover, Germany. RP Bruder, D (reprint author), German Res Ctr Biotechnol, Dept Mucosal Immun, Mascheroder Weg 1, D-38124 Braunschweig, Germany. EM dbr@gbf.de NR 39 TC 71 Z9 75 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2005 VL 54 IS 12 BP 3395 EP 3401 DI 10.2337/diabetes.54.12.3395 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988HB UT WOS:000233582500007 PM 16306354 ER PT J AU Qi, L Meigs, J Manson, JE Ma, J Hunter, D Rifai, N Hu, FB AF Qi, L Meigs, J Manson, JE Ma, J Hunter, D Rifai, N Hu, FB TI HFE genetic variability, body iron stores, and the risk of type 2 diabetes in US women SO DIABETES LA English DT Article ID HEMOCHROMATOSIS CANDIDATE GENE; HEREDITARY HEMOCHROMATOSIS; H63D MUTATIONS; C282Y MUTATION; PROSPECTIVE COHORT; SERUM FERRITIN; POPULATION; MELLITUS; PREVALENCE; ABSORPTION AB To determine whether the HFE gene variants H63D and C282Y are associated with body iron stores and the risk of type 2 diabetes, we conducted a nested case-control study of 714 incident cases of type 2 diabetes and 1,120 matching control subjects in a prospective cohort, the Nurses' Health Study. In both healthy control and diabetic case subjects, H63D homozygosity, C282Y, and the compound heterozygotes were associated with significantly higher levels of plasma ferritin and significantly lower ratios of transferrin receptors to ferritin. Such effects were independent of age, BMI, and lifestyle factors. Overall, there were no significant differences in genotypes of H63D and C282Y between the case and control subjects. A meta-analysis of 4,245 case and 5,982 control subjects indicated a null association of C282Y with diabetes risk, whereas carriers of H63D or the compound heterozygotes had marginally increased risk (odds ratio [OR] 1.11 [95% Cl 1.00-1.25] and 1.60 [0.99-2.60], respectively). In addition, we found a significant interaction between HFE variants and heme iron intake (P for interaction = 0.029). The ORs of type 2 diabetes across increasing quartiles of heme iron were 1.00, 1.21 (0.72-2.01), 1.72 (1.03-2.88), and 1.49 (0.91-2.46) among the participants with either the H63D or C282Y variant, whereas the ORs were 1.00, 0.71 (0.49-1.05), 1.12 (0.76-1.66), and 0.96 (0.65-1.42) among those with wild-type genotypes. Our data indicate significant effects of H63D and C282Y on body iron stores and suggest a potential interaction between HFE genotypes and heme iron intake in relation to the risk of type 2 diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845] NR 44 TC 26 Z9 28 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2005 VL 54 IS 12 BP 3567 EP 3572 DI 10.2337/diabetes.54.12.3567 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988HB UT WOS:000233582500030 PM 16306377 ER PT J AU Brooks-Worrell, B Goel, A Chin, H Palmer, J AF Brooks-Worrell, B Goel, A Chin, H Palmer, J TI Metabolic and immunological comparisons between autoimmune and nonautoimmune diabetes SO DIABETES LA English DT Meeting Abstract CT 6th Servier-IGIS Symposium CY MAR 10-13, 2005 CL St Jean Cap Ferrat, FRANCE C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM bbrooks@u.washington.edu NR 0 TC 0 Z9 0 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 DEC PY 2005 VL 54 SU 2 MA 01 BP S159 EP S159 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990EZ UT WOS:000233727300023 ER PT J AU Adams, AS Zhang, F Mah, C Grant, RW Kleinman, K Meigs, JB Ross-Degnan, D AF Adams, AS Zhang, F Mah, C Grant, RW Kleinman, K Meigs, JB Ross-Degnan, D TI Race differences in long-term diabetes management in an HMO SO DIABETES CARE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; AFRICAN-AMERICAN ADULTS; GLYCEMIC CONTROL; ETHNIC-DIFFERENCES; SOCIAL SUPPORT; CARE; DISPARITIES; MELLITUS; POPULATION; NIDDM AB OBJECTIVE- We examined race differences in diabetes outcomes over 4-8 years in a single HMO. RESEARCH DESIGN AND METHODS - We identified black and white adult diabetic patients who were continuously enrolled (1992-2001) and in whom diabetes was 1) diagnose before 1994 (n = 1,686) or 2) newly diagnosed in 1994-1997 (n = 1,280). We used hierarchical models to estimate the effect of race on average annual HbA(1C) (A1C) controlling for baseline A1C BMI, and age, as well as annual measures of type of diabetes medications, diabetes-relate hospitalization, time and the number of A1C tests, physician visits, and nondiabetes medications. Stratifying by sex accounted for significant interactions between sex and race. RESULTS - At baseline, black and white patients had similar rates of A1C testing and physician visits, but blacks had higher unadjusted A1C values. In multivariate models, among patients with previously diagnosed diabetes, average A1C was nonsignificantly 0.11 higher (95% CI -0.12 to 0.34) in black than in white men but was 0.30 higher (0.14-0.46; P = 0.0007) in black than in white women. Among patients with newly diagnosed diabetes, the adjusted black-white gap was 0.49 among men (0.17-0.80; P = 0.007) and was 0.05 among women (-0.20 to -0.31), which was positive but not significant. CONCLUSIONS - Factors other than the quality of care may explain persistent race differences in A1C in this setting. Future interventions should target normalization of A1C by identifying potential psychosocial barriers to therapy intensification among patients and clinicians and development of culturally appropriate interventions to aid patients in successful self-management. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Adams, AS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM aadams@hms.harvard.edu OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK 067452, K23 DK067452, K23 DK067452-01A1]; NIMHD NIH HHS [L60 MD000756] NR 44 TC 32 Z9 32 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2005 VL 28 IS 12 BP 2844 EP 2849 DI 10.2337/diacare.28.12.2844 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988HJ UT WOS:000233583500005 PM 16306543 ER EF