FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schmucker, D Flanagan, JG AF Schmucker, D Flanagan, JG TI Generation of recognition diversity in the nervous system SO NEURON LA English DT Editorial Material ID DROSOPHILA DSCAM; AXON GUIDANCE; RECEPTOR; ADHESION; GENES AB For decades, it has been suggested that complex neural wiring might be specified by extensive diversity in receptor isoforms. Dscam is a cell surface protein with 38,016 potential alternatively spliced isoforms in the fly nervous system. Remarkable binding studies now show that Dscam isoform diversity indeed results in an unprecedented level of recognition diversity, showing isoform-specific homophilic binding. In vivo studies have begun to suggest models for use of Dscam diversity in neuron-target recognition, axon fasciculation, and neuron self-recognition. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Schmucker, D (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM dietmar_schmucker@dfci.harvard.edu; flanagan@hms.harvard.edu NR 15 TC 20 Z9 23 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 14 PY 2004 VL 44 IS 2 BP 219 EP 222 DI 10.1016/j.neuron.2004.10.004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 864LU UT WOS:000224635800005 PM 15473961 ER PT J AU Hutter-Paier, B Huttunen, HJ Puglielli, L Eckman, CB Kim, DY Hofmeister, A Moir, RD Domnitz, SB Frosch, MP Windisch, M Kovacs, DM AF Hutter-Paier, B Huttunen, HJ Puglielli, L Eckman, CB Kim, DY Hofmeister, A Moir, RD Domnitz, SB Frosch, MP Windisch, M Kovacs, DM TI The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease SO NEURON LA English DT Article ID SECRETASE-LIKE CLEAVAGE; PRECURSOR-PROTEIN; TRANSGENIC MICE; BETA-PROTEIN; IN-VITRO; CHOLESTEROL; PRESENILIN-1; DEPOSITION; APP; PURIFICATION AB Amyloid beta-peptide (Abeta) accumulation in specific brain regions is a pathological hallmark of Alzheimer's disease (AD). We have previously reported that a well characterized acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, CP-113,818, inhibits Abeta production in cell-based experiments. Here, we assessed the efficacy of CP-113,818 in reducing AD-like pathology in the brains of transgenic mice expressing human APP(751) containing the London (V7171) and Swedish (K670M/N671L) mutations. Two months of treatment with CP-113,818 reduced the accumulation of amyloid plaques by 88%-99% and membrane/insoluble Abeta levels by 83%-96%, while also decreasing brain cholesteryl-esters by 86%. Additionally, soluble Abeta(42) was reduced by 34% in brain homogenates. Spatial learning was slightly improved and correlated with decreased Abeta levels. In nontransgenic littermates, CP-113,818 also reduced ectodomain shedding of endogenous APP in the brain. Our results suggest that ACAT inhibition may be effective in the prevention and treatment of AD by inhibiting generation of the Abeta peptide. C1 Harvard Univ, Sch Med, Neurobiol Dis Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. JSW Res Forsch Labor GmbH, Inst Expt Pharmacol, A-8020 Graz, Austria. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Neurobiol Dis Lab, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu OI Huttunen, Henri/0000-0002-9867-4438 NR 45 TC 148 Z9 154 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 14 PY 2004 VL 44 IS 2 BP 227 EP 238 DI 10.1016/j.neuron.2004.08.043 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 864LU UT WOS:000224635800007 PM 15473963 ER PT J AU Kinane, TB Westra, SJ AF Kinane, TB Westra, SJ TI A four-year-old boy with hypoxemia - Hepatopulmonary syndrome due to the Abernethy malformation, type 1. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PULMONARY ARTERIOVENOUS-MALFORMATIONS; HEREDITARY HEMORRHAGIC TELANGIECTASIA; LIVER-TRANSPLANTATION; CONGENITAL ABSENCE; PORTAL-VEIN; ANGIOGRAPHY; CT; CIRRHOSIS; DISEASE; SHUNT C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. NR 29 TC 25 Z9 25 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 OCT 14 PY 2004 VL 351 IS 16 BP 1667 EP 1675 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 861OU UT WOS:000224427300015 PM 15483286 ER PT J AU Levine, RA AF Levine, RA TI Dynamic mitral regurgitation - More than meets the eye SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DYSFUNCTION C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 6 TC 38 Z9 39 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 OCT 14 PY 2004 VL 351 IS 16 BP 1681 EP 1684 DI 10.1056/NEJMe048165 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 861OU UT WOS:000224427300018 PM 15483289 ER PT J AU Subramanian, S West, RB Corless, CL Ou, WB Rubin, BP Chu, KM Leung, SY Yuen, ST Zhu, S Hernandez-Boussard, T Montgomery, K Nielsen, TO Patel, RM Goldblum, JR Heinrich, MC Fletcher, JA van de Rijn, M AF Subramanian, S West, RB Corless, CL Ou, WB Rubin, BP Chu, KM Leung, SY Yuen, ST Zhu, S Hernandez-Boussard, T Montgomery, K Nielsen, TO Patel, RM Goldblum, JR Heinrich, MC Fletcher, JA van de Rijn, M TI Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles SO ONCOGENE LA English DT Article DE GIST; KIT; PDGFRA; mutations; microarray; gene expression ID OF-FUNCTION MUTATIONS; SIGNAL-TRANSDUCTION; C-KIT; ERM PROTEINS; CANCER; IMATINIB; SITE; MICROARRAYS; MODULATION; APOPTOSIS AB Most GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that might contribute to these biological differences, we carried out gene expression profiling of 26 GISTs with known KIT and PDGFRA mutational status. Expression differences were then evaluated further by RNA in situ hybridization, immunohistochemistry, and immunoblotting. Unsupervised hierarchical clustering grouped tumors with similar mutations together, but the distinction between the different groups was not absolute. Differentially expressed genes included ezrin, p70S6K, and PKCs, which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute to the distinctive clinicopathological features in GISTs with different mutation types. These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated. C1 Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. Oregon Hlth & Sci Univ, OHSU Canc Inst, Dept Pathol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Washington, Med Ctr, Dept Anat Pathol, Seattle, WA 98195 USA. Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Stanford Univ, Med Ctr, Dept Biochem, Stanford, CA 94305 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada. Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. Oregon Hlth & Sci Univ, OHSU Canc Inst, Dept Med, Portland, OR 97201 USA. RP van de Rijn, M (reprint author), Stanford Univ, Med Ctr, Dept Pathol, L-235,300 Pasteur Dr, Stanford, CA 94305 USA. EM mrijn@stanford.edu RI Chu, Kent/C-4251-2009; Yuen , Siu /K-6311-2014; Leung, Suet Yi/C-4340-2009 FU NCI NIH HHS [CA85129] NR 47 TC 95 Z9 98 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 OCT 14 PY 2004 VL 23 IS 47 BP 7780 EP 7790 DI 10.1038/sj.onc.1208056 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 860GX UT WOS:000224331600004 PM 15326474 ER PT J AU Arancio, O Zhang, HP Chen, X Lin, C Trinchese, F Puzzo, D Liu, SM Hegde, A Yan, SF Stern, A Luddy, JS Lue, LF Walker, DG Roher, A Buttini, M Mucke, L Li, WY Schmidt, AM Kindy, M Hyslop, PA Stern, DM Du Yan, SS AF Arancio, O Zhang, HP Chen, X Lin, C Trinchese, F Puzzo, D Liu, SM Hegde, A Yan, SF Stern, A Luddy, JS Lue, LF Walker, DG Roher, A Buttini, M Mucke, L Li, WY Schmidt, AM Kindy, M Hyslop, PA Stern, DM Du Yan, SS TI RAGE potentiates A beta-induced perturbation of neuronal function in transgenic mice SO EMBO JOURNAL LA English DT Article DE neuroinflammation; neuronal degeneration; NF-kappa B activation; synaptic plasticity ID NF-KAPPA-B; AMYLOID-PRECURSOR-PROTEIN; ALZHEIMERS-DISEASE; OXIDANT STRESS; SYNAPTIC PLASTICITY; PLAQUE-FORMATION; GENE-EXPRESSION; RECEPTOR; ACTIVATION; PEPTIDE AB Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta). In view of increased neuronal expression of RAGE in Alzheimer's disease, a murine model was developed to assess the impact of RAGE in an Ab-rich environment, employing transgenics (Tgs) with targeted neuronal overexpression of RAGE and mutant amyloid precursor protein (APP). Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice. In contrast, Tg mice bearing a dominant-negative RAGE construct targeted to neurons crossed with mAPP animals displayed preservation of spatial learning/memory and diminished neuropathologic changes. These data indicate that RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction. C1 Columbia Univ, Coll Phys & Surg, Taub Inst Alzheimers Dis & Aging Brain, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. NYU, Sch Med, Dementia Res Ctr,nathan Kline Inst, Dept Psychiat Physiol & Neurosci, New York, NY USA. NYU, Dept Neurol, New York, NY USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA. Sun Hlth Res Inst, Sun City, AZ USA. Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. Eli Lilly & Co, Dept Neurosci, Indianapolis, IN 46285 USA. Med Univ S Carolina, Inst Neurosci, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Coll Georgia, Sch Med, Augusta, GA 30912 USA. RP Du Yan, SS (reprint author), Columbia Univ, Coll Phys & Surg, Taub Inst Alzheimers Dis & Aging Brain, Dept Pathol, 630 W 168th St, New York, NY 10032 USA. EM sdy1@columbia.edu OI PUZZO, Daniela/0000-0002-9542-2251 FU CSR NIH HHS [IIRG-00-2076]; NIA NIH HHS [K07 AG000959, 1KO7AG00959, AG16223, AG17490, AG18345, AG60901, P01 AG017490, R01 AG018345] NR 36 TC 184 Z9 194 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 13 PY 2004 VL 23 IS 20 BP 4096 EP 4105 DI 10.1038/sj.emboj.7600415 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867BG UT WOS:000224816500018 PM 15457210 ER PT J AU O'Donnell, CJ AF O'Donnell, CJ TI Family history, subclinical atherosclerosis, and coronary heart disease risk - Barriers and opportunities for the use of family history information in risk prediction and prevention SO CIRCULATION LA English DT Editorial Material DE editorials; genetics; risk factors; coronary disease; prevention ID INTIMA-MEDIA THICKNESS; PARENTAL CARDIOVASCULAR-DISEASE; BEAM COMPUTED-TOMOGRAPHY; MYOCARDIAL-INFARCTION; WOMEN; HERITABILITY; ACCURACY; EVENTS; ADULTS; DEATH C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov NR 21 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 12 PY 2004 VL 110 IS 15 BP 2074 EP 2076 DI 10.1161/01.CIR.0000145539.77021.AC PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 861HP UT WOS:000224407000001 PM 15477424 ER PT J AU Evgenov, OV Ichinose, F Evgenov, NV Gnoth, MJ Falkowski, GE Chang, YC Bloch, KD Zapol, WM AF Evgenov, OV Ichinose, F Evgenov, NV Gnoth, MJ Falkowski, GE Chang, YC Bloch, KD Zapol, WM TI Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs SO CIRCULATION LA English DT Article DE hypertension, pulmonary; enzymes; vasodilation; nitric oxide; hemodynamics ID CARBON-MONOXIDE AB Background-Inhaled nitric oxide (NO) is a potent and selective pulmonary vasodilator, which induces cGMP synthesis by activating soluble guanylate cyclase (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to influence smooth muscle tone via activation of sGC. We examined whether direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO. Methods and Results-In awake, instrumented lambs, the thromboxane analogue U-46619 was intravenously administered to increase mean pulmonary arterial pressure to 35 mm Hg. Intravenous infusion of BAY 41-2272 (0.03, 0.1, and 0.3 mg.kg(-1).h(-1)) reduced mean pulmonary arterial pressure and pulmonary vascular resistance and increased transpulmonary cGMP release in a dose-dependent manner. Larger doses of BAY 41-2272 also produced systemic vasodilation and elevated the cardiac index. N-omega-nitro-L-arginine methyl ester abolished the systemic but not the pulmonary vasodilator effects of BAY 41-2272. Furthermore, infusing BAY 41-2272 at 0.1 mg.kg(-1).h(-1) potentiated and prolonged the pulmonary vasodilation induced by inhaled NO (2, 10, and 20 ppm). In contrast, inhaled CO (50, 250, and 500 ppm) had no effect on U-46619-induced pulmonary vasoconstriction before or during administration of BAY 41-2272. Conclusions-In lambs with acute pulmonary hypertension, BAY 41-2272 is a potent pulmonary vasodilator that augments and prolongs the pulmonary vasodilator response to inhaled NO. Direct pharmacological stimulation of sGC, either alone or in combination with inhaled NO, may provide a novel approach for the treatment of pulmonary hypertension. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Bayer HealthCare AG, Pharma Res Ctr, Wuppertal, Germany. RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 309, Boston, MA 02114 USA. EM evgenov@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [HL42397, HL71987, HL74352] NR 17 TC 68 Z9 71 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 12 PY 2004 VL 110 IS 15 BP 2253 EP 2259 DI 10.1161/01.CIR.0000144469.01521.8A PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 861HP UT WOS:000224407000030 PM 15466650 ER PT J AU Walhovd, KB Fjell, AM Reinvang, I Lundervold, A Fischl, B Quinn, BT Dale, AM AF Walhovd, KB Fjell, AM Reinvang, I Lundervold, A Fischl, B Quinn, BT Dale, AM TI Size does matter in the long run - Hippocampal and cortical volume predict recall across weeks SO NEUROLOGY LA English DT Article ID MEMORY PERFORMANCE; IN-VIVO; SPATIAL MEMORY; GRAY-MATTER; HUMAN BRAIN; AGE; MRI; RETRIEVAL; DECADES; SEX AB Objective: To study the morphometric determinants of recall of verbal material for an extended period in an adult lifespan sample. Methods: Healthy adults of varying ages were studied using automated segmentation of MRI scans with volumes of hippocampus, cortex, and white matter, and verbal memory tests assessing recall after 5 minutes, 30 minutes, and a mean period of 11 weeks. Stepwise regression analyses were performed with 5 minutes, 30 minutes, and 11-week recall as the dependent variables. Hippocampal, cortical, and white matter volumes were included in the initial set of predictor variables in each case, and the analyses were repeated with age as an additional predictor variable. Results: When age was not included, cortical volume was the only variable predicting recall after 5 and 30 minutes, whereas hippocampal and cortical volumes predicted recall after 11 weeks. When age was included in the model, this was the only variable predicting recall after 5 and 30 minutes, whereas age and hippocampus gave contributions in prediction of recall after several weeks. Conclusion: This study supports a critical role of cortical and hippocampal size in recall. Hippocampal size seems more important in recall after 11 weeks than after a shorter time interval. C1 Univ Oslo, Dept Psychol, N-0317 Oslo, Norway. Ullevaal Univ Hosp, Dept Neuropsychol, Oslo, Norway. Rikshosp Univ Hosp, Dept Psychosomat Med, Oslo, Norway. Univ Bergen, Dept Physiol & Locus Neurosci, N-5020 Bergen, Norway. Harvard Univ, Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02115 USA. Norwegian Univ Sci & Technol, MR Ctr, N-7034 Trondheim, Norway. RP Walhovd, KB (reprint author), Univ Oslo, Dept Psychol, POB 1094, N-0317 Oslo, Norway. EM kristine@walhovd.com RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR14075, R01-RR13609, R01-RR16594]; NINDS NIH HHS [R01-NS39581] NR 37 TC 34 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 2004 VL 63 IS 7 BP 1193 EP 1197 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 861HV UT WOS:000224408000011 PM 15477537 ER PT J AU Vucic, S Black, KR Chong, PST Cros, D AF Vucic, S Black, KR Chong, PST Cros, D TI Multifocal motor neuropathy - Decrease in conduction blocks and reinnervation with long-term IVIg SO NEUROLOGY LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN TREATMENT; DOUBLE-BLIND; IMMUNE GLOBULIN; DEMYELINATING NEUROPATHY; FOLLOW-UP; CYCLOPHOSPHAMIDE; THERAPY; COMPLICATIONS; DIAGNOSIS; DISEASE AB Background: Multifocal motor neuropathy with conduction blocks (MMNCB) is an immune-mediated motor neuropathy. Previous long-term IV immunoglobulin (IVIg) treatment studies have documented improvement in muscle strength and functional disability but revealed a concomitant increase in acute axonal degeneration ( AD) and conduction block ( CB). Objective: To determine the long-term effects of IVIg therapy on clinical and neurophysiologic outcome measures in MMNCB patients responsive to IVIg. Methods: The authors reviewed medical records of 10 patients with MMNCB for outcomes in muscle strength (Medical Research Council score), functional disability (Modified Rankin Disability score), CB, and AD. All patients had received IVIg (2g/kg in 5 days for 3 consecutive months), followed by monthly maintenance therapy. Results: Patients were followed for an average of 7.25 years (range, 3.5 to 12 years). There was significant and sustained improvement in muscle strength and functional disability while on IVIg therapy. Furthermore, the authors found significant improvement in CB, decrease in AD, and evidence of reinnervation by the end of the follow-up period. Conclusion: Long-term IV immunoglobulin therapy improves muscle strength and functional disability, decreases the number of conduction blocks and the extent of axonal degeneration, and promotes reinnervation. These findings differ from previous reports of deterioration in neurophysiologic outcome measures. Comparison of the IV immunoglobulin regimen in those reports and this study shows that the authors' patients were treated with significantly higher IV immunoglobulin maintenance doses. These findings have implications for the long-term treatment of patients with multifocal motor neuropathy with conduction blocks. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. EM dcros@partners.org NR 32 TC 74 Z9 76 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 2004 VL 63 IS 7 BP 1264 EP 1269 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 861HV UT WOS:000224408000023 PM 15477549 ER PT J AU Takeoka, M Riviello, JJ Duffy, FH Kim, F Kennedy, DN Makris, N Caviness, VS Holmes, GL AF Takeoka, M Riviello, JJ Duffy, FH Kim, F Kennedy, DN Makris, N Caviness, VS Holmes, GL TI Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome SO NEUROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Epilepsy-Society CY DEC 01, 2000 CL Los Angeles, CA SP Amer Epilespy Soc ID HUMAN NEOCORTEX; ABNORMALITIES AB No specific anatomic abnormalities have been detected in typical Landau-Kleffner syndrome (LKS), an acquired epileptic aphasia with language regression in children. In four children with typical LKS without obvious anatomic abnormalities, the authors performed MRI volumetric analysis of various neocortical regions and subcortical substructures. Volume reduction was detected in bilateral superior temporal areas (26 to 51%), specifically in planum temporale (25 to 63%) and superior temporal gyrus (25 to 57%), where receptive language is localized. C1 Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Sch Law, Childrens Mem Hosp, Dept Med Imaging, Chicago, IL 60611 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Neurol, Hanover, NH 03756 USA. RP Takeoka, M (reprint author), Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, 300 Longwood Ave,Hunnewell 2, Boston, MA 02115 USA. EM maxtakeoka@aol.com NR 10 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 2004 VL 63 IS 7 BP 1289 EP 1292 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 861HV UT WOS:000224408000029 PM 15477555 ER PT J AU Bastepe, M Weinstein, LS Ogata, N Kawaguchi, H Juppner, H Kronenberg, HM Chung, UI AF Bastepe, M Weinstein, LS Ogata, N Kawaguchi, H Juppner, H Kronenberg, HM Chung, UI TI Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; XL-ALPHA-S; PARATHYROID-HORMONE; MATERNAL TRANSMISSION; PTH/PTHRP RECEPTOR; GENE; EXPRESSION; SUBUNIT; PSEUDOHYPOPARATHYROIDISM AB Stimulatory heterotrimeric G protein (Gs) transduces signals from various cell-surface receptors to adenylyl cyclases, which generate cAMP. The a subunit of Gs (Gsalpha) is encoded by GNAS (Gnas in mice), and heterozygous Gsa inactivating mutations lead to Albright hereditary osteodystrophy. The in vivo role of Gsa in skeletogenesis is largely unknown, because of early embryonic lethality of mice with disruption of Gnas exon 2 (Gnas(E2-)/E2-) and the absence of easily detectable phenotypes in growth plate chondrocytes of heterozygous mutant mice (Gnas(+)/(E2-)). We generated chimeric mice containing wild-type cells and either Gnas(E2-)/(E2-) or Gnas(+/E2-) cells. Gnas(E2-)/(E2-) chondrocytes phenocopied PTH/PTHrP receptor (PPR)(-/-) cells by prematurely undergoing hypertrophy. Introduction of a transgene expressing Gsa, one of several gene products that include Gnas exon 2, into Gnas(E2-)/(E2-) cells prevented premature hypertrophy. Gsa mRNA expression detected by real-time RT-PCR analysis was reduced to approximately half that of the wild-type in both paternal and maternal Gnas(+)/(E2-) growth plate chondrocytes, indicating biallelic expression of Gsa in these cells. Hypertrophy of Gnas(+)/(E2-) chondrocytes was modestly but significantly premature in chimeric growth plates of mice containing wild-type and Gnas(+)/(E2-) cells. These data suggest that Gsa is the primary mediator of the actions of PPR in growth plate chondrocytes and that there is haploinsufficiency of Gsa signaling in Gnas(+)/(E2-) chondrocytes. C1 Tokyo Univ Hosp, Div Tissue Engn, Bunkyo Ku, Tokyo 1138655, Japan. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chung, UI (reprint author), Tokyo Univ Hosp, Div Tissue Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM teiy-ort@h.u-tokyo.ac.jp OI Weinstein, Lee/0000-0002-1899-5152 FU NIAMS NIH HHS [AR47078, R01 AR047078]; NIDDK NIH HHS [R37 DK046718, P01 DK056246, DK46718, R56 DK046718, DK56246, R01 DK046718] NR 29 TC 81 Z9 83 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 OCT 12 PY 2004 VL 101 IS 41 BP 14794 EP 14799 DI 10.1073/pnas.0405091101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 862JX UT WOS:000224488000022 PM 15459318 ER PT J AU Kahle, KT MacGregor, GG Wilson, FH Van Hoek, AN Brown, D Ardito, T Kashgarian, M Giebisch, G Hebert, SC Boulpaep, EL Lifton, RF AF Kahle, KT MacGregor, GG Wilson, FH Van Hoek, AN Brown, D Ardito, T Kashgarian, M Giebisch, G Hebert, SC Boulpaep, EL Lifton, RF TI Paracellular Cl- permeability is regulated by WNK4 kinase: Insight into normal physiology and hypertension SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein serine-threonine kinases; ion transport ID TIGHT JUNCTION FUNCTION; CHLORIDE REABSORPTION; MUTANT WNK4; EXPRESSION; PROTEIN; CLAUDINS; SODIUM; CELLS; HYPERKALEMIA; EPITHELIA AB Paracellular ion flux across epithelia occurs through selective and regulated pores in tight junctions; this process is poorly understood. Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia. Whereas WNK4 is known to regulate several transcellular transporters and channels involved in NaCl and K+ homeostasis, its localization to tight junctions suggests it might also regulate paracellular flux. We performed electrophysiology on mammalian kidney epithelia with inducible expression of various WNK4 constructs. Induction of wild-type WNK4 reduced transepithelial resistance by increasing absolute chloride permeability. PHAII-mutant WNK4 produced markedly larger effects, whereas kinase-mutant WNK4 had no effect. The electrochemical and pharmacologic properties of these effects indicate they are attributable to the paracellular pathway. The effects of WNK4 persist when induction is delayed until after tight-junction formation, demonstrating a dynamic effect. WNK4 did not alter the flux of uncharged solutes, or the expression or localization of selected tight-junction proteins. Transmission and freeze-fracture electron microscopy showed no effect of WNK4 on tight-junction structure. These findings implicate WNK signaling in the coordination of transcellular and paracellular flux to achieve NaCl and K+ homeostasis, explain PHAII pathophysiology,and suggest that modifiers of WNK signaling may be potent anti hypertensive agents. C1 Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lifton, RF (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, 1 Gilbert St, New Haven, CT 06510 USA. EM richard.lifton@yale.edu NR 39 TC 116 Z9 117 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 2004 VL 101 IS 41 BP 14877 EP 14882 DI 10.1073/pnas.040672101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 862JX UT WOS:000224488000036 PM 15465913 ER PT J AU Hamar, P Song, EW Kokeny, G Chen, A Ouyang, NT Lieberman, J AF Hamar, P Song, EW Kokeny, G Chen, A Ouyang, NT Lieberman, J TI Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION; MAMMALIAN-CELLS; ACTIVATION; APOPTOSIS; KIDNEY; SIRNA; DNA AB Fas-mediated apoptosis has been suggested to contribute to tubular cell death after renal ischemia-reperfusion injury. Here we investigate whether small interfering RNA (siRNA) duplexes targeting Fas protect mice from acute renal failure after clamping of the renal artery. Renal ischemia-reperfusion injury was induced by clamping the renal vein and artery for 15 or 35 min. Mice were treated before or after ischemia with siRNA targeting Fas or a control gene, administered by hydrodynamic injection, low-volume renal vein injection, or both. Treated mice were evaluated for renal Fas protein and mRNA expression, tissue histopathology, and apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. Blood urea nitrogen and survival were monitored in mice in which the contralateral kidney had been removed. A single hydrodynamic injection of Fas siRNA reduced Fas mRNA and protein expression in the kidney 4-fold. Kidneys from mice that received Fas siRNA two days earlier had substantially less renal tubular apoptosis by TUNEL staining and less tubular atrophy and hyaline damage. Whereas 90% of mice pretreated with saline or GFP siRNA died, only 20% of Fas-siRNA-pretreated animals died. The same survival advantage was provided by a single low-volume Fas siRNA injection into the renal vein. Moreover, postischemic injection through the renal vein protected 38% of mice from death. This study confirms the importance of Fas-mediated apoptosis in renal ischemia-reperfusion injury. Silencing Fas by systemic or local catheterization holds therapeutic promise to limit ischemia-reperfusion injury. C1 Semmelweis Univ, Inst Pathophysiol, H-1089 Budapest, Hungary. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. Inst Canc Prevent, Valhalla, NY 10595 USA. RP Semmelweis Univ, Inst Pathophysiol, Nagyvarad Ter 4, H-1089 Budapest, Hungary. EM hampet@net.sote.hu RI Kokeny, Gabor/E-8881-2011; Lieberman, Judy/A-2717-2015; Hamar, Peter/A-8996-2010; OI Hamar, Peter/0000-0002-1095-3564; Kokeny, Gabor/0000-0002-0345-6914 FU NIAID NIH HHS [AI-056900, U19 AI056900] NR 18 TC 175 Z9 184 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 2004 VL 101 IS 41 BP 14883 EP 14888 DI 10.1073/pnas.040621101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 862JX UT WOS:000224488000037 PM 15466709 ER PT J AU Liu, G Zhou, W Wang, LI Park, S Miller, DP Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC AF Liu, G Zhou, W Wang, LI Park, S Miller, DP Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC TI MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma SO CANCER LETTERS LA English DT Article DE MPO; SOD2; polymorphism; gender; lung cancer ID MANGANESE SUPEROXIDE-DISMUTASE; MYELOPEROXIDASE (-463)G->A POLYMORPHISM; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CANCER RISK; CIGARETTE-SMOKING; REDUCED RISK; GENETIC POLYMORPHISMS; OXIDATIVE STRESS; PROMOTER REGION; MALE SMOKERS AB Manganese superoxide dismutase (SOD2) and myeloperoxidase (MPO) are polymorphic enzymes involved in reactive oxidative species metabolism. In this case-control study (830 non-small cell lung carcinoma (NSCLC) patients; 1119 controls) we evaluated whether the MPO-G463A polymorphism (associated with a novel estrogen receptor binding site) modifies the association between the SOD2 Ala16Val polymorphism and NSCLC risk differently by gender. For women carrying the MPO variant genotypes, the adjusted odds ratio of the SOD2 polymorphism (Val/Val vs. Ala/Ala) was 3.26 (95% Cl, 1.55-6.83). No associations were found in men or in women carrying the MPO GG wildtype genotype. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Massachusetts Gen Hosp,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA074386, CA90578]; NIEHS NIH HHS [ES/CA 06409, ES00002]; PHS HHS [T3206709] NR 53 TC 36 Z9 38 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 8 PY 2004 VL 214 IS 1 BP 69 EP 79 DI 10.1016/j.canlet.2004.06.027 PG 11 WC Oncology SC Oncology GA 857UY UT WOS:000224145500008 PM 15331175 ER PT J AU Li, Q Dai, XD Shen, PY Cantiello, HF Karpinski, E Chen, XZ AF Li, Q Dai, XD Shen, PY Cantiello, HF Karpinski, E Chen, XZ TI A modified mammalian tandem affinity purification procedure to prepare functional polycystin-2 channel SO FEBS LETTERS LA English DT Article DE tandem affinity purification; mammalian cell; planar lipid bilaver; polycystin-2; electrophysiology ID PROTEIN COMPLEX PURIFICATION; CATION CHANNEL; IDENTIFICATION; PROTEOMICS; EXPRESSION; INTERACTS; YEAST; CELLS; PKD2 AB The tandem affinity purification (TAP) procedure was initially developed as a tool for rapid purification of native protein complexes expressed at their natural levels in yeast cells. This purification procedure was also applied to study interactions between soluble proteins in mammalian cells. In order to apply this procedure to mammalian membrane proteins, we created a modified TAP tag expression vector and fused with the PKD2 gene, encoding a membrane cation channel protein, polycystin-2, mutated in 15% of autosomal dominant polycystic kidney disease. We generated epithelial Madin-Darby canine kidney cell line stably expressing TAP-tagged polycystin-2, improved the subsequent steps for membrane protein release and stability, and succeeded in purifying this protein. Using patch clamp electrophysiology we detected specific polycystin-2 channel activities when the purified protein was reconstituted into a lipid bilayer system. Thus, this modified TAP procedure provides a powerful alternative to functionally characterize membrane proteins, such as ion channels, transporters and receptors, using cell-free system derived from mammalian cells. (C) 2004 Published by, Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Alberta, Dept Physiol, Edmonton, AB T6G 2H7, Canada. Massachusetts Gen Hosp, Renal Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Chen, XZ (reprint author), Univ Alberta, Dept Physiol, 7-29 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. EM xzchen@ualberta.ca NR 21 TC 13 Z9 15 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 8 PY 2004 VL 576 IS 1-2 BP 231 EP 236 DI 10.1016/j.febslet.2004.09.017 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 864BM UT WOS:000224607800045 PM 15474043 ER PT J AU Boxem, M Tsai, CW Zhang, Y Saito, RM Liu, JO AF Boxem, M Tsai, CW Zhang, Y Saito, RM Liu, JO TI The C elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation SO FEBS LETTERS LA English DT Article DE map-1; map-2; methionine aminopeptidase; germline development ID ANGIOGENESIS INHIBITOR TNP-470; CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; TRANSLATION INITIATION; GENETIC INTERFERENCE; 67-KDA POLYPEPTIDE; SYNTHETIC ANALOGS; TUMOR-GROWTH; FUMAGILLIN AB We have investigated the physiological function of type 2 methionine aminopeptidases (MetAP2) using Caenorhabditis elegans as a model system. A homolog of human MetAP2 was found in the C. elegans genome, which we termed MAP-2. MAP-2 protein displayed methionine aminopeptidase activity and was sensitive to inhibition by fumagillin. Downregulation of map-2 expression by RNAi led to sterility, resulting from a defect in germ cell proliferation. These observations suggest that MAP-2 is essential for germ cell development in C elegans and that this ubiquitous enzyme may play important roles in a tissue specific manner. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Liu, JO (reprint author), Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, E Baltimore Campus,Room 516,Hunterian Bldg,725 N, Baltimore, MD 21205 USA. EM joliu@jhu.edu RI Boxem, Mike/B-8857-2011 OI Boxem, Mike/0000-0003-3966-4173 FU NCI NIH HHS [CA078743] NR 35 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 8 PY 2004 VL 576 IS 1-2 BP 245 EP 250 DI 10.1016/j.febslet.2004.08.077 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 864BM UT WOS:000224607800047 PM 15474045 ER PT J AU Yan, Q Kamura, T Cai, Y Jin, JJ Ivan, M Mushegian, A Conaway, RC Conaway, JW AF Yan, Q Kamura, T Cai, Y Jin, JJ Ivan, M Mushegian, A Conaway, RC Conaway, JW TI Identification of Elongin C and Skp1 sequences that determine Cullin selection SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; UBIQUITIN-LIGASE COMPLEX; HYPOXIA-INDUCIBLE FACTOR; KAPPA-B-ALPHA; SOCS-BOX MOTIF; F-BOX; PROTEASOME PATHWAY; FACTOR 1-ALPHA; HIF-ALPHA; SCF AB The multiprotein von Hippel-Lindau (VHL) tumor suppressor and Skp1-Cul1-F-box protein (SCF) complexes belong to families of structurally related E3 ubiquitin ligases. In the VHL ubiquitin ligase, the VHL protein serves as the substrate recognition subunit, which is linked by the adaptor protein Elongin C to a heterodimeric Cul2/Rbx1 module that activates ubiquitylation of target proteins by the E2 ubiquitin-conjugating enzyme Ubc5. In SCF ubiquitin ligases, F-box proteins serve as substrate recognition subunits, which are linked by the Elongin C-like adaptor protein Skp1 to a Cul1/Rbx1 module that activates ubiquitylation of target proteins, in most cases by the E2 Cdc34. In this report, we investigate the functions of the Elongin C and Skp1 proteins in reconstitution of VHL and SCF ubiquitin ligases. We identify Elongin C and Skp1 structural elements responsible for selective interaction with their cognate Cullin/Rbx1 modules. In addition, using altered specificity Elongin C and F-box protein mutants, we investigate models for the mechanism underlying E2 selection by VHL and SCF ubiquitin ligases. Our findings provide evidence that E2 selection by VHL and SCF ubiquitin ligases is determined not solely by the Cullin/Rbx1 module, the target protein, or the integrity of the substrate recognition subunit but by yet to be elucidated features of these macromolecular complexes. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan. Tufts New England Med Ctr, Dept Med, Mol Oncol Res Inst, Boston, MA 02111 USA. Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA. RP Conaway, JW (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. EM jlc@stowers-institute.org RI Ivan, Mircea/A-8109-2012; Yan, Qin/E-8893-2012; OI Yan, Qin/0000-0003-4077-453X; Conaway, Joan/0000-0002-2786-0663; Mushegian, Arcady/0000-0002-6809-9225 FU NIGMS NIH HHS [R37 GM041628] NR 49 TC 9 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 8 PY 2004 VL 279 IS 41 BP 43019 EP 43026 DI 10.1074/jbc.M408018200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858XQ UT WOS:000224226400084 PM 15280393 ER PT J AU Weng, AP Ferrando, AA Lee, W Morris, JP Silverman, LB Sanchez-Irizarry, C Blacklow, SC Look, AT Aster, JC AF Weng, AP Ferrando, AA Lee, W Morris, JP Silverman, LB Sanchez-Irizarry, C Blacklow, SC Look, AT Aster, JC TI Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia SO SCIENCE LA English DT Article ID GAMMA-SECRETASE; TRANSCRIPTIONAL ACTIVATION; TRANSGENIC MICE; PROTEIN; COMPLEX; INACTIVATION; PRESENILIN; INDUCTION; RECEPTORS; DOMAINS AB Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. RP Aster, JC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM jaster@rics.bwh.harvard.edu RI Weng, Andrew/I-5015-2014; Ferrando, Adolfo /Q-7026-2016 FU NCI NIH HHS [CA68484, CA109901, CA21765, CA82308, CA94233, CA98093, P01 CA109901] NR 25 TC 1461 Z9 1512 U1 12 U2 80 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 OCT 8 PY 2004 VL 306 IS 5694 BP 269 EP 271 DI 10.1126/science.1102160 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 861MC UT WOS:000224419700038 PM 15472075 ER PT J AU Sloan, KE Eustace, BK Stewart, JK Zehetmeier, C Torella, C Simeone, M Roy, JE Unger, C Louis, DN Ilag, LL Jay, DG AF Sloan, KE Eustace, BK Stewart, JK Zehetmeier, C Torella, C Simeone, M Roy, JE Unger, C Louis, DN Ilag, LL Jay, DG TI CD155/PVR plays a key role in cell motility during tumor cell invasion and migration SO BMC CANCER LA English DT Article ID HUMAN POLIOVIRUS RECEPTOR/CD155; ASSISTED LIGHT INACTIVATION; EXPRESSION; CANCER; METASTASIS; ADHESION; GENE; INTEGRINS; NECTIN; IDENTIFICATION AB Background: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. Methods: We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation ( FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Results: Using this screen, we have identified CD155 ( the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and alphav-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. Conclusion: These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis. C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Xer Pharmaceut AG, Munich, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jay, DG (reprint author), Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. EM kevin.sloan@tufts.edu; brenda.eustace@tufts.edu; jean.stewart@tufts.edu; c.zehetmeier@xerion-pharma.com; c.torella@xerion-pharma.com; marina.simeone@tufts.edu; royj@helix.mgh.harvard.edu; c.unger@xerion-pharma.com; dlouis@partners.org; l.ilag@xerion-pharma.com; daniel.jay@tufts.edu NR 41 TC 93 Z9 96 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD OCT 7 PY 2004 VL 4 AR 73 DI 10.1186/1471-2407-4-73 PG 14 WC Oncology SC Oncology GA 868UR UT WOS:000224939000002 PM 15471548 ER PT J AU Rosen, FS AF Rosen, FS TI Conquering polio - Isolation of poliovirus - John Enders and the nobel prize. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosen, FS (reprint author), Childrens Hosp, Ctr Blood Res, 300 Longwood Ave, Boston, MA 02115 USA. NR 5 TC 5 Z9 5 U1 0 U2 7 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 OCT 7 PY 2004 VL 351 IS 15 BP 1481 EP 1483 DI 10.1056/NEJMp048202 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 859UP UT WOS:000224293700002 PM 15470207 ER PT J AU Benz, EJ AF Benz, EJ TI Genotypes and phenotypes - Another lesson from the hemoglobinopathies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 3 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 OCT 7 PY 2004 VL 351 IS 15 BP 1490 EP 1492 DI 10.1056/NEJMp048198 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 859UP UT WOS:000224293700006 PM 15470211 ER PT J AU Geva, A Clark, JJ Zhang, YX Popowicz, A Manning, JM Neufeld, EJ AF Geva, A Clark, JJ Zhang, YX Popowicz, A Manning, JM Neufeld, EJ TI Brief report: Hemoglobin Jamaica Plain - A sickling hemoglobin with reduced oxygen affinity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID S ANTILLES; DISEASE AB A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA sequencing of the (beta) globin gene revealed that her maternal (beta) globin allele was normal. Her paternal allele had not only the expected sickle-trait mutation, (beta)(sup Glu6Val), but also a second, charge-neutral mutation, (beta)(sup Leu68Phe). Analysis of the patient's hemoglobin revealed that the double-mutant protein, which we called ``hemoglobin Jamaica Plain,'' had severely reduced oxygen affinity. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen. C1 Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. RP Neufeld, EJ (reprint author), Childrens Hosp Boston, Div Hematol Oncol, Karp 8210,300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; OI Geva, Alon/0000-0002-8574-0133 FU NHLBI NIH HHS [HL18819, HL04184] NR 14 TC 20 Z9 21 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 OCT 7 PY 2004 VL 351 IS 15 BP 1532 EP 1538 DI 10.1056/NEJMoa040771 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 859UP UT WOS:000224293700011 PM 15470216 ER PT J AU Kratz, A Ferraro, M Sluss, PM Lewandrowski, KB AF Kratz, A Ferraro, M Sluss, PM Lewandrowski, KB TI Laboratory reference value SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pathol, Clin Hematol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunodiagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kratz, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Clin Hematol Lab, Boston, MA 02114 USA. NR 1 TC 238 Z9 245 U1 1 U2 10 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 OCT 7 PY 2004 VL 351 IS 15 BP 1548 EP 1563 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 859UP UT WOS:000224293700014 PM 15470219 ER PT J AU Cambria, RP AF Cambria, RP TI Stenting for carotid-artery stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENDARTERECTOMY; TRIAL C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. NR 9 TC 31 Z9 31 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 OCT 7 PY 2004 VL 351 IS 15 BP 1565 EP 1567 DI 10.1056/NEJMe048234 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 859UP UT WOS:000224293700015 PM 15470220 ER PT J AU Stankovic, K Rio, C Xia, AP Sugawara, M Adams, JC Liberman, MC Corfas, G AF Stankovic, K Rio, C Xia, AP Sugawara, M Adams, JC Liberman, MC Corfas, G TI Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuregulin; cochlea; hearing; GDNF; neurotrophin; erbB ID SCHWANN-CELLS; NEUROTROPHIC FACTOR; CARDIAC DEVELOPMENT; NEUROMUSCULAR-JUNCTION; NEUREGULIN RECEPTOR; AUDITORY NEUROPATHY; SENSORY EPITHELIUM; MICE LACKING; IN-VIVO; EXPRESSION AB Degeneration of cochlear sensory neurons is an important cause of hearing loss, but the mechanisms that maintain the survival of adult cochlear sensory neurons are not clearly defined. We now provide evidence implicating the neuregulin (NRG)-erbB receptor signaling pathway in this process. We found that NRG1 is expressed by spiral ganglion neurons (SGNs), whereas erbB2 and erbB3 are expressed by supporting cells of the organ of Corti, suggesting that these molecules mediate interactions between these cells. Transgenic mice in which erbB signaling in adult supporting cells is disrupted by expression of a dominant-negative erbB receptor show severe hearing loss and 80% postnatal loss of type-I SGNs without concomitant loss of the sensory cells that they contact. Quantitative RT-PCR analysis of neurotrophic factor expression shows a specific downregulation in expression of neurotrophin-3 (NT3) in the transgenic cochleas before the onset of neuronal death. Because NT3 is critical for survival of type I SGNs during development, these results suggest that it plays similar roles in the adult. Together, the data indicate that adult cochlear supporting cells provide critical trophic support to the neurons, that survival of postnatal cochlear sensory neurons depends on reciprocal interactions between neurons and supporting cells, and that these interactions are mediated by NRG and neurotrophins. C1 Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Tohoku Univ, Grad Sch Med, Dept Otolaryngol Head & Neck Surg, Sendai, Miyagi 9808574, Japan. RP Corfas, G (reprint author), Childrens Hosp, Div Neurosci, 300 Longwood Ave, Boston, MA 02115 USA. EM gabriel.corfas@childrens.harvard.edu FU NIDCD NIH HHS [P30 DC005209, R01 DC04820] NR 61 TC 105 Z9 108 U1 2 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 6 PY 2004 VL 24 IS 40 BP 8651 EP 8661 DI 10.1523/JNEUROSCI.0733-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 859YK UT WOS:000224304100002 PM 15470130 ER PT J AU O'Connell, JB Maggard, MA Ko, CY AF O'Connell, JB Maggard, MA Ko, CY TI Colon cancer survival rates with the new American Joint Committee on cancer sixth edition staging SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECTAL-CANCER; COLORECTAL-CANCER; LYMPH-NODES; HIGH-RISK; NUMBER; PROGNOSIS AB Background: The recently revised American Joint Committee on Cancer (AJCC) sixth edition cancer staging system increased the stratification within colon cancer stages II and III defined by the AJCC fifth edition system. Using nationally representative Surveillance, Epidemiology, and End Results (SEER) data, we compared survival rates associated with colon cancer stages defined according to both AJCC systems. Methods: Using SEER data (from January 1, 1991, through December 31, 2000), we identified 119 363 patients with colon adenocarcinoma and included all patients in two analyses by stages defined by AJCC fifth and sixth edition systems. Tumors were stratified by SEER's "extent of disease" and "number of positive [lymph] nodes" coding schemes. Kaplan-Meier analyses were used to compare overall and stage-specific 5-year survival. All statistical tests were two-sided. Results: Overall 5-year survival was 65.2%. According to stages defined by the AJCC fifth edition system, 5-year stage-specific survivals were 93.2% for stage I, 82.5% for stage II, 59.5% for stage III, and 8.1% for stage IV. According to stages defined by the AJCC sixth edition system, 5-year stage-specific survivals were 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage IIb, 83.4% for stage IIIa, 64.1 % for stage IIIb, 44.3 % for stage IIIc, and 8.1 % for stage IV. Under the sixth edition system, 5-year survival was statistically significantly better for patients with stage IIIa colon cancer (83.4%) than for patients with stage IIb disease (72.2%) (P<.001). Conclusions: The AJCC sixth edition system for colon cancer stratifies survival more distinctly than the fifth edition system by providing more substages. The association of stage IIIa colon cancer with statistically Significantly better survival than stage IIb in the new system may reflect current clinical practice, in which stage III patients receive chemotherapy but stage II patients generally do not. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Hosp, Dept Surg, Los Angeles, CA USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Rm 72-215 CHS, Los Angeles, CA 90095 USA. EM jbocjboc@hotmail.com NR 17 TC 745 Z9 780 U1 2 U2 21 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 OCT 6 PY 2004 VL 96 IS 19 BP 1420 EP 1425 DI 10.1093/jnci/djh275 PG 6 WC Oncology SC Oncology GA 859YM UT WOS:000224304300008 PM 15467030 ER PT J AU Terasawa, T Blackmore, CC Bent, S Kohlwes, RJ AF Terasawa, T Blackmore, CC Bent, S Kohlwes, RJ TI Systematic review: Computed tomography and ultrasonography to detect acute appendicitis in adults and adolescents SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SUSPECTED ACUTE APPENDICITIS; ABDOMINAL SONOGRAPHY; DIAGNOSTIC-TESTS; HELICAL CT; US; METAANALYSIS; ACCURACY; ULTRASOUND; DECISION; PATIENT AB Background: Although clinicians commonly use computed tomography or ultrasonography to diagnose acute appendicitis, the accuracy of these imaging tests remains unclear. Purpose: To review the diagnostic accuracy of computed tomography and ultrasonography in adults and adolescents with suspected acute appendicitis. Data Sources: The authors used MEDLINE, EMBASE, bibliographies, review articles, textbooks, and expert opinion to retrieve English- and non-English-language articles published from 1966 to December 2003. Study Selection: The authors included prospective studies evaluating computed tomography or ultrasonography followed by surgical confirmation or clinical follow-up in patients at least 14 years of age with suspected appendicitis. Data Extraction: One assessor (for non-English-language studies) or 2 assessors (for English-language studies) independently reviewed each article to abstract relevant study characteristics and results. Data Synthesis: Twelve computed tomography studies and 14 ultrasonography studies met inclusion criteria. Computed tomography had an overall sensitivity of 0.94 (95% Cl, 0.91 to 0.95), a specificity of 0.95 (Cl, 0.93 to 0.96), a positive likelihood ratio of 13.3 (Cl, 9.9 to 17.9), and a negative likelihood ratio of 0.09 (Cl, 0.07 to 0.12). Ultrasonography had an overall sensitivity of 0.86 (Cl, 0.83 to 0.88), a specificity of 0.81 (Cl, 0.78 to 0.84), a positive likelihood ratio of 5.8 (Cl, 3.5 to 9.5), and a negative likelihood ratio of 0.19 (Cl, 0.13 to 0.27). Verification bias and inappropriate blinding of reference standards were noted in all of the included studies. Limitations: The summary assessment of the diagnostic accuracy for both tests was limited by the small number of studies, heterogeneity among study samples, and poor methodologic quality in the original studies. Conclusions: Computed tomography is probably more accurate than ultrasonography for diagnosing appendicitis in adults and adolescents. Prospective studies that apply gold standard diagnostic testing to all study participants would more reliably estimate the true diagnostic accuracy of these tests. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. RP Terasawa, T (reprint author), Nagoya Natl Hosp, Dept Clin Res & Hematol, Naka Ku, 4-1-1 Sannomaru, Nagoya, Aichi 4600001, Japan. EM terasawa@nnh.hosp.go.jp FU AHRQ HHS [K08-HS11291]; NCCIH NIH HHS [1 K08-AT001338-01] NR 45 TC 143 Z9 149 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 5 PY 2004 VL 141 IS 7 BP 537 EP 546 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 862CR UT WOS:000224467800006 PM 15466771 ER PT J AU Snow, V Barry, P Fihn, SD Gibbons, RJ Owens, DK Williams, SV Mottur-Pilson, C Weiss, KB AF Snow, V Barry, P Fihn, SD Gibbons, RJ Owens, DK Williams, SV Mottur-Pilson, C Weiss, KB CA Amer Coll of Physicians TI Primary care management of chronic stable angina and asymptomatic suspected or known coronary artery disease: A clinical practice guideline from the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ASSOCIATION TASK-FORCE; HIGH-RISK PATIENTS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; ANTIPLATELET THERAPY; CHOLESTEROL LEVELS; RANDOMIZED TRIALS; SILENT ISCHEMIA; HEART-FAILURE; DOUBLE-BLIND AB In 1999, the American College of Physicians (ACP), then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the second of 2 that provide guidance on the management of patients with chronic stable angina. This document covers treatment and follow-up of symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A previous guideline covered diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months and asymptomatic patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. C1 Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ Penn, Philadelphia, PA 19104 USA. Merck Inst Aging & Hlth, Washington, DC USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Mayo Clin, Rochester, MN USA. Vet Affairs Hlth Care Syst, Palo Alto, CA USA. Edward Hines Jr Vet Adm Hosp, Chicago, IL USA. Northwestern Univ, Chicago, IL 60611 USA. RP Snow, V (reprint author), Amer Coll Physicians, 192 N Independence Mall W, Philadelphia, PA 19106 USA. EM vincenza@mail.acponline.org NR 27 TC 37 Z9 48 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 5 PY 2004 VL 141 IS 7 BP 562 EP 567 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 862CR UT WOS:000224467800009 PM 15466774 ER PT J AU Balady, GJ Larson, MG Vasan, RS Leip, EP O'Donnell, CJ Levy, D AF Balady, GJ Larson, MG Vasan, RS Leip, EP O'Donnell, CJ Levy, D TI Usefulness of exercise testing in the prediction of coronary disease risk among asymptomatic persons as a function of the Framingham risk score SO CIRCULATION LA English DT Article DE exercise; risk factors; cardiovascular diseases ID ALL-CAUSE MORTALITY; HEART-DISEASE; CHRONOTROPIC INCOMPETENCE; CARDIOVASCULAR-DISEASE; PRIMARY-PREVENTION; PHYSICAL-ACTIVITY; FOLLOW-UP; MEN; ASSOCIATION; CAPACITY AB Background - The purpose of this study is to determine the usefulness of exercise treadmill testing (ETT) among asymptomatic persons in predicting coronary heart disease (CHD) events over and above the Framingham CHD risk score. Methods and Results - Subjects included 3043 members of the Framingham Heart Study offspring cohort without CHD ( 1431 men and 1612 women; age, 45 +/- 9 years) who underwent ETT and were followed up for 18.2 years. The risk of developing CHD was evaluated relative to 3 exercise test variables: ( 1) ST-segment depression greater than or equal to 1 mm, ( 2) failure to achieve target heart rate (THR) of 85% predicted maximum, and ( 3) exercise capacity. In multivariable analyses that adjusted for age and Framingham CHD risk score, among men, ST-segment depression ( hazard ratio [HR], 1.88; 95% CI, 1.21 to 2.91) and failure to achieve THR (HR, 1.70; 95% CI, 1.18 to 2.45) predicted higher CHD risk, whereas a greater exercise capacity predicted lower CHD risk ( HR per MET, 0.94; 95% CI, 0.89 to 0.99). Although similar HRs were seen in women, those results were not statistically significant. Among men with 10-year predicted risk greater than or equal to20%, failure to reach THR and ST-segment depression both more than doubled the risk of an event ( HR, 2.66 and HR, 2.11, respectively), and each MET increment in exercise capacity reduced risk by 13% ( HR, 0.87). Conclusions - Among asymptomatic men, ST-segment depression, failure to reach THR, and exercise capacity during ETT provided additional prognostic information in age- and Framingham risk score - adjusted models, particularly among those in the highest risk group ( 10-year predicted CHD risk of greater than or equal to 20%). The evaluation of exercise test variables in women is limited, given our sample size and the few CHD events in women. C1 Boston Univ, Sch Med, Boston Med Ctr, Dept Med,Sect Cardiol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Balady, GJ (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Med,Sect Cardiol, 88 E Newton St, Boston, MA 02118 USA. EM gary.balady@bmc.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K-24-HL-04334, N01-HC-25195] NR 33 TC 98 Z9 101 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 5 PY 2004 VL 110 IS 14 BP 1920 EP 1925 DI 10.1161/01.CIR.0000143226.40607.71 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 859KM UT WOS:000224262100009 PM 15451778 ER PT J AU Fukumoto, Y Deguchi, J Libby, P Rabkin-Aikawa, E Sakata, Y Chin, MT Hill, CC Lawler, PR Varo, N Schoen, FJ Krane, SM Aikawa, M AF Fukumoto, Y Deguchi, J Libby, P Rabkin-Aikawa, E Sakata, Y Chin, MT Hill, CC Lawler, PR Varo, N Schoen, FJ Krane, SM Aikawa, M TI Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques SO CIRCULATION LA English DT Article ID SMOOTH-MUSCLE-CELLS; MATRIX-METALLOPROTEINASE ACTIVITY; ANEURYSM FORMATION; TISSUE INHIBITOR; BALLOON INJURY; DEFICIENT MICE; HUMAN ATHEROMA; EXPRESSION; MACROPHAGES; MIGRATION AB Background - We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques. Methods and Results - To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E - deficient mice (apoE(-/-)) that express collagenase-resistant collagen-I (Col(R/R)/ apoE(-/-), n = 12) or wild-type collagen-expressing mice (Col(+/+)/ apoE(-/-), n = 12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from Col(R/R)/apoE(-/-) mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of Col(R/R)/apoE(-/-) mice contained significantly more intimal collagen than did those of Col(+/+)/ apoE(-/-) mice. Conclusion - These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Aikawa, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Donald W Reynolds Cardiovasc Clin Res Ctr, 77 Ave Louis Pasteur,NRB741, Boston, MA 02115 USA. EM maikawa@rics.bwh.harvard.edu OI Lawler, Patrick/0000-0001-5155-5071 FU NHLBI NIH HHS [P01 HL-48743, HL-56985]; NIAMS NIH HHS [AR-44185] NR 36 TC 51 Z9 52 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 5 PY 2004 VL 110 IS 14 BP 1953 EP 1959 DI 10.1161/01.CIR.0000143174.41810.10 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 859KM UT WOS:000224262100014 PM 15451791 ER PT J AU Shibata, S Lee, JT AF Shibata, S Lee, JT TI Tsix transcription- versus RNA-based mechanisms in Xist repression and epigenetic choice SO CURRENT BIOLOGY LA English DT Article ID X-CHROMOSOME INACTIVATION; INTERGENIC TRANSCRIPTION; ANTISENSE TRANSCRIPTION; GENE; MOUSE; EXPRESSION; LOCUS; MICE; ELEMENTS; NUCLEUS AB Recent inquiries have revealed a surprisingly large number (>2500) of naturally occurring antisense transcripts [1-4], but their function remains largely undiscovered. A better understanding of antisense mechanisms is clearly needed because of their potentially diverse roles in gene regulation and disease [5-8]. A well-documented case occurs in X inactivation, the mechanism by which X-linked gene expression is equalized between XX females and XY males [9]. The antisense gene Tsix [6] determines X chromosome choice and represses the noncoding silencer, Xist [10-12]. In principle, Tsix action may involve RNA, the act of transcription, or local chromatin. Here, we create novel Tsix alleles to distinguish transcription-versus RNA-based mechanisms. When Tsix transcription is terminated before Xist (Tsix(TRAP)), Tsix cannot block Xist upregulation, suggesting the importance of overlapping antisense transcription. To separate the act of transcription from RNA, we knocked in Tsix cDNA in the reverse orientation (Tsix(cDNA)) to restore RNA levels in cis without concurrent transcription across Xist. However, Tsix(cDNA) cannot complement Tsix(TRAP). Surprisingly, both mutations disrupt choice, indicating that this epigenetic step requires transcription. We conclude that the processed antisense RNA does not act alone and that Tsix function specifically requires antiparallel transcription through Xist. A mechanism of transcription-based feedback regulation is proposed. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@frodo.mgh.harvard.edu FU NIGMS NIH HHS [R01-GM58839] NR 32 TC 61 Z9 65 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 5 PY 2004 VL 14 IS 19 BP 1747 EP 1754 DI 10.1016/j.cub.2004.09.053 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 860QM UT WOS:000224358100023 PM 15458646 ER PT J AU Gemma, C Stellwagen, H Fister, M Coultrap, SJ Mesches, MH Browning, MD Bickford, PC AF Gemma, C Stellwagen, H Fister, M Coultrap, SJ Mesches, MH Browning, MD Bickford, PC TI Rosiglitazone improves contextual fear conditioning in aged rats SO NEUROREPORT LA English DT Article DE aging; contextual fear conditioning; IL-1 beta memory; PPAR gamma agonists; rosiglitazone ID ACTIVATED-RECEPTOR-GAMMA; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; ANTIINFLAMMATORY DRUGS; INFLAMMATORY PROCESSES; EXPRESSION; AGONISTS; INSULIN; BETA; PATHOGENESIS AB Experimental, clinical, and epidemiologic studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are beneficial in Alzheimer's disease and other neuroinflammatory processes. One possible mechanism is an interaction with peroxisome proliferator-activated receptors (PPARs). We examined the effect of a specific PPARgamma agonist, rosiglitazone, on contextual fear conditioning in aged rats. Male rats (20-months-old) were administered rosiglitazone in the diet for 2 months prior to behavioral testing. Young control and aged rats fed rosiglitazone froze significantly more than did the aged control rats in a hippocampal-dependent fear conditioning task. Rosiglitazone had no effect hippocampal interleukin-1beta levels, markers of oxidative damage, and NMDA receptor expression. Therefore, activation of PFARgamma prevented age-related deficits in hippocampal function. C1 Univ S Florida, Dept Neurosurg, Ctr Excellence Aging & Brain Repair, Tampa, FL 33612 USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80220 USA. RP Bickford, PC (reprint author), Univ S Florida, Dept Neurosurg, Ctr Excellence Aging & Brain Repair, 12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM pbickfor@hsc.usf.edu RI Bickford, Paula/J-5970-2012; OI Bickford, Paula/0000-0001-9657-7725; Gemma, Carmelina/0000-0002-4480-0056 FU NIA NIH HHS [AG04418] NR 25 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 5 PY 2004 VL 15 IS 14 BP 2255 EP 2259 DI 10.1097/00001756-200410050-00023 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 871NW UT WOS:000225141400023 PM 15371745 ER PT J AU Chen, J DeAngelo, DJ Kutok, JL Williams, IR Lee, BH Wadleigh, M Duclos, N Cohen, S Adelsperger, J Okabe, R Coburn, A Galinsky, I Huntly, B Cohen, PS Meyer, T Fabbro, D Roesel, J Banerji, L Griffin, JD Xiao, S Fletcher, JA Stone, RM Gilliland, DG AF Chen, J DeAngelo, DJ Kutok, JL Williams, IR Lee, BH Wadleigh, M Duclos, N Cohen, S Adelsperger, J Okabe, R Coburn, A Galinsky, I Huntly, B Cohen, PS Meyer, T Fabbro, D Roesel, J Banerji, L Griffin, JD Xiao, S Fletcher, JA Stone, RM Gilliland, DG TI PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; PROTEIN-KINASE; TRANSFORMING ACTIVITY; T(6/8) TRANSLOCATION; SIGNAL-TRANSDUCTION; IMATINIB MESYLATE; FGFR1; GENE; EXPRESSION AB Human stem cell leukemia-lymphoma syndrome usually presents itself as a myeloproliferative disorder (MPD) that evolves to acute myeloid leukemia and/or lymphoma. The syndrome associated with t(8;13)(p11;q12) results in expression of the ZNF198-fibroblast growth factor receptor (FGFR) 1 fusion tyrosine kinase. Current empirically derived cytotoxic chemotherapy is inadequate for treatment of this disease. We hypothesized that small-molecule inhibitors of the ZNF198-FGFR1 fusion would have therapeutic efficacy. We characterized the transforming activity of ZNF198-FGFR1 in hematopoietic cells in vitro and in vivo. Expression of ZNF198-FGFR1 in primary murine hematopoietic cells caused a myeloproliferative syndrome in mice that recapitulated the human MPD phenotype. Transformation in these assays, and activation of the downstream effector molecules PLC-gamma, STAT5, and phosphatidylinositol 3-kinase/AKT, required the proline-rich domains, but not the ZNF domains, of ZNF198. A small-molecule tyrosine kinase inhibitor, PKC412 (N-benzoyl-staurosporine) effectively inhibited ZNF198-FGFR1 tyrosine kinase activity and activation of downstream effector pathways, and inhibited proliferation of ZNF198-FGFR1 transformed Ba/F3 cells. Furthermore, treatment with PKC412 resulted in statistically significant prolongation of survival in the murine model of ZNF198-FGFR1-induced MPD. Based in part on these data, PKC412 was administered to a patient with t(8;13)(p11;q12) and was efficacious in treatment of progressive myeloproliferative disorder with organomegaly. Therefore, PKC412 may be a useful therapy for treatment of human stem cell leukemia-lymphoma syndrome. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. 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. Novartis Pharma AG, Florham Pk, NJ 07932 USA. Novartis Pharma AG, CH-4002 Basel, Switzerland. RP Stone, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM rstone@partners.org; 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 [CA 66996, P01 CA066996]; NIDDK NIH HHS [DK 50654, P01 DK050654] NR 30 TC 119 Z9 129 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 5 PY 2004 VL 101 IS 40 BP 14479 EP 14484 DI 10.1073/pnas.0404438101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 860UR UT WOS:000224369600032 PM 15448205 ER PT J AU Matthews, BD LaVan, DA Overby, DR Karavitis, J Ingber, DE AF Matthews, BD LaVan, DA Overby, DR Karavitis, J Ingber, DE TI Electromagnetic needles with submicron pole tip radii for nanomanipulation of biomolecules and living cells SO APPLIED PHYSICS LETTERS LA English DT Article ID MAGNETIC NANOPARTICLES; FOCAL ADHESIONS AB We describe the design and fabrication of a temperature-controlled electromagnetic microneedle (EMN) to generate custom magnetic field gradients for biomedical and biophysical applications. An electropolishing technique was developed to sharpen the EMN pole tip to any desired radius between 100 nm and 20 mum. The EMN can be used to apply strong static or dynamic forces (>50 nN) to micrometer- or nanometer-sized magnetic beads without producing significant heating or needle movement. Large tip radii (20 mum) allow magnetic force application to multiple magnetic beads over a large area, while small radii (0.1-6 mum) can be used to selectively pull or capture single magnetic beads from within a large population of similar particles. The customizable EMN is thus well suited for micro- and nanomanipulation of magnetic particles linked to biomolecules or living cells. (C) 2004 American Institute of Physics. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol,Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Yale Univ, Dept Mech Engn, New Haven, CT 06511 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. RP Matthews, BD (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol,Vasc Biol Program, Boston, MA 02115 USA. EM Donald.ingber@childrens.harvard.edu RI Overby, Darryl/G-1520-2011; LaVan, David/C-3943-2012 OI Overby, Darryl/0000-0001-9894-7515; LaVan, David/0000-0002-1952-0028 NR 13 TC 36 Z9 37 U1 0 U2 15 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD OCT 4 PY 2004 VL 85 IS 14 BP 2968 EP 2970 DI 10.1063/1.1802383 PG 3 WC Physics, Applied SC Physics GA 863FV UT WOS:000224547300098 ER PT J AU Fleischmann, J Liu, H Wu, CP AF Fleischmann, J Liu, H Wu, CP TI Polyadenylation of ribosomal RNA by Candida albicans also involves the small subunit SO BMC MOLECULAR BIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; POLYMERASE SWITCH; YEAST; RDNA AB Background: Candida albicans is a polymorphic fungus causing serious infections in immunocompromised patients. It is capable of shifting from yeast to germinating forms such as hypha and pseudohypha in response to a variety of signals, including mammalian serum. We have previously shown that some of the large 25S components of ribosomal RNA in Candida albicans get polyadenylated, and this process is transiently intensified shortly after serum exposure just prior to the appearance of germination changes. Results: We now present data that this process also involves the small 18S subunit of ribosomal RNA in this organism. Unlike the large 25S subunit, polyadenylation sites near the 3' end are more variable and no polyadenylation was found at the reported maturation site of 18S. Similar to 25S, one or more polyadenylated mature sized 18S molecules get intensified transiently by serum just prior to the appearance of hypha. Conclusions: The transient increase in polyadenylation of both the large and the small subunits of ribosomal RNA just prior to the appearance of hypha, raises the possibility of a role in this process. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Dent, Dept Oral Biol & Med, Los Angeles, CA 90095 USA. RP Fleischmann, J (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jfl@ucla.edu; biye@ucla.edu; hivictorwu@yahoo.com NR 14 TC 12 Z9 14 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD OCT 4 PY 2004 VL 5 AR 17 DI 10.1186/1471-2199-5-17 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 862AK UT WOS:000224461100001 PM 15461824 ER PT J AU Jamerson, MH Johnson, MD Korsmeyer, SJ Furth, PA Dickson, RB AF Jamerson, MH Johnson, MD Korsmeyer, SJ Furth, PA Dickson, RB TI Baxregulates c-Myc-induced mammary tumour apoptosis but not proliferation in MMTV-c-myc transgenic mice SO BRITISH JOURNAL OF CANCER LA English DT Article DE Bax; c-Myc; transgenic mice; mammary gland; apoptosis; tumorigenesis ID GROWTH-FACTOR-ALPHA; CHANNEL-FORMING ACTIVITY; BCL-2 GENE FAMILY; MOUSE MAMMARY; BREAST-CANCER; CYTOCHROME-C; TGF-ALPHA; GLAND INVOLUTION; EPITHELIAL-CELLS; IN-VIVO AB The expression of the proto-oncogene c-myc is frequently deregulated, via multiple mechanisms, in human breast cancers. Deregulated expression of c-myc contributes to mammary epithelial cell transformation and is causally involved in mammary tumorigenesis in MMTV-c-myc transgenic mice. c-Myc is known to promote cellular proliferation, apoptosis, genomic instability and tumorigenesis in several distinct tissues, both in vivo and in vitro. Expression of the proapoptotic regulatory gene bax is reduced or absent in human breast cancers, and c-Myc has been shown to regulate the expression of Bax, as well as cooperate with Bax in controlling apoptosis in a fibroblast model. Additionally, loss of bax reduces c-Myc-induced apoptosis in lymphoid cells and increases c-Myc-mediated lymphomagenesis in vivo. In order to assess whether loss of bax could influence c-Myc-induced apoptosis and tumorigenesis in the mammary gland in vivo, we generated MMTV-c-myc transgenic mice in which neither, one, or both wild-type alleles of bax were eliminated. Haploid loss of bax in MMTV-c-myc transgenic mice resulted in significantly reduced mammary tumour apoptosis. As anticipated for an apoptosis-regulatory gene, loss of the wild-type bax alleles did not significantly alter cellular proliferation in either mammary adenocarcinomas or dysplastic mammary tissues. However, in contrast to c-Myc-mediated lymphomagenesis, loss of one or both alleles of bax in MMTV-c-myc transgenic mice did not significantly enhance mammary tumorigenesis, despite evidence that haploid loss of bax might modestly increase mammary tumour multiplicity. Our results demonstrate that Bax contributes significantly to c-Myc-induced apoptosis in mammary tumours. In addition, they suggest that in contrast to c-Myc-induced lymphomagenesis, mammary tumorigenesis induced by deregulated c-myc expression requires some amount of Bax expression. C1 Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Harvard Univ, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Dickson, RB (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3970 Reservoir Rd NW, Washington, DC 20057 USA. EM DicksonR@georgetown.edu FU NCI NIH HHS [1R01CA72460, T32 CA009686, 2T32CA09686, R01 CA072460]; NIA NIH HHS [1R01AG1496] NR 71 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 4 PY 2004 VL 91 IS 7 BP 1372 EP 1379 DI 10.1038/sj.bjc.6602137 PG 8 WC Oncology SC Oncology GA 859GC UT WOS:000224250400022 PM 15354213 ER PT J AU Stokol, T O'Donnell, P Xiao, L Knight, S Stavrakis, G Botto, M von Andrian, UH Mayadas, TN AF Stokol, T O'Donnell, P Xiao, L Knight, S Stavrakis, G Botto, M von Andrian, UH Mayadas, TN TI C1q governs deposition of circulating immune complexes and leukocyte Fc gamma receptors mediate subsequent neutrophil recruitment SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE antigen-antibody complex; Fc receptors; animal models; coniplement 1q; microscopy ID P-SELECTIN; IN-VIVO; COORDINATE EXPRESSION; INDUCED INFLAMMATION; ADHESION MOLECULES; CELL RECRUITMENT; ARTHUS REACTION; DEFICIENT MICE; COMPLEMENT; VASCULITIS AB Inflammation induced by circulating immunoglobulin G-immune complexes (ICs) characterizes many immune-mediated diseases. In this work, the molecular requirements for the deposition of circulating ICs and subsequent acute leukocyte recruitment in mice were elucidated. We show that after intravenous injection, preformed soluble ICs are rapidly deposited in the postcapillary venules of the cremaster microcirculation, secondary to increased vascular permeability. This deposition is dependent on complement C1.q. IC deposition is associated with leukocyte recruitment. Leukocyte rolling, which is mediated by P-selectin in the exteriorized cremaster muscle, is not further increased in response to ICs. In contrast, leukocyte rolling velocity is significantly decreased and leukocyte adhesion is significantly increased in the presence of ICs. The IC-mediated slow leukocyte rolling velocity and subsequent adhesion and emigration are dependent on Fcgamma receptors (FcgammaPs), particularly FcgammaRIII, with complement C3 and C5 having no detectable role. These studies suggest a regulatory mechanism of IC deposition and leukocyte trafficking in IC-mediated inflammation requiring C1q and FcgammaRs in sequential, noninteracting roles. C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Fac Med, Rheumatol Sect, London SW7 2AZ, England. RP Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, 77 Ave Louis Pasteur,7520 NRB, Boston, MA 02115 USA. EM tmayadas@rics.bwh.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [F32 HL067570, HL-67570, HL036028, HL65095, P01 HL036028, R01 HL065095]; NIDDK NIH HHS [DK51643, R01 DK051643] NR 62 TC 36 Z9 37 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD OCT 4 PY 2004 VL 200 IS 7 BP 835 EP 846 DI 10.1084/jem.20040501 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 860YN UT WOS:000224380700002 PM 15466618 ER PT J AU Ling, KW Ottersbach, K van Hamburg, JP Oziemlak, A Tsai, FY Orkin, SH Ploemacher, R Hendricks, RW Dzierzak, E AF Ling, KW Ottersbach, K van Hamburg, JP Oziemlak, A Tsai, FY Orkin, SH Ploemacher, R Hendricks, RW Dzierzak, E TI GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic stem cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE GATA-2; hematopoietic stem cells; AGM; haploinsufficiency; gene dosage ID TRANSCRIPTION FACTOR GATA-2; FETAL LIVER HEMATOPOIESIS; MOUSE EMBRYO; DEFINITIVE HEMATOPOIESIS; AGM REGION; YOLK-SAC; EXPRESSION; DIFFERENTIATION; GENE; MICE AB GATA-2 is an essential transcription factor in the hematopoietic system that is expressed in hematopoietic stern cells (HSCs) and progenitors. Complete deficiency of GATA-2 in the mouse leads to severe anemia and embryonic lethality. The role of GATA-2 and dosage effects of this transcription factor in HSC development within the embryo and adult are largely unexplored. Here we examined the effects of GATA-2 gene dosage on the generation and expansion of HSCs in several hematopoietic sites throughout mouse development. We show that a haploid dose of GATA-2 severely reduces production and expansion of HSCs specifically in the aorta-gonad-mesonephros region (which autonomously generates the first HSCs), whereas quantitative reduction of HSCs is minimal or unchanged in yolk sac, fetal liver, and adult bone marrow. However, HSCs in all these ontogenically distinct anatomical sites are qualitatively defective in serial or competitive transplantation assays. Also, cytotoxic drug-induced regeneration studies show a clear GATA-2 dose-related proliferation defect in adult bone marrow. Thus, GATA-2 plays at least two functionally distinct roles during ontogeny of HSCs: the production and expansion of HSCs in the aorta-gonad-mesonephros and the proliferation of HSCs in the adult bone marrow. C1 Erasmus Univ, Med Ctr, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Immunol, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Hematol, NL-3000 DR Rotterdam, Netherlands. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dzierzak, E (reprint author), Erasmus Univ, Med Ctr, Dept Cell Biol & Genet, POB 1738, NL-3000 DR Rotterdam, Netherlands. EM e.dzierzak@eramusmc.nl RI van Hamburg, Jan Piet/B-8446-2009; OI Ottersbach, Katrin/0000-0002-6880-4895 FU NIDDK NIH HHS [R01 DK51077] NR 39 TC 153 Z9 158 U1 2 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 4 PY 2004 VL 200 IS 7 BP 871 EP 882 DI 10.1084/jem.20031556 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 860YN UT WOS:000224380700005 PM 15466621 ER PT J AU Yun, SH Tearney, GJ de Boer, JF Bouma, BE AF Yun, SH Tearney, GJ de Boer, JF Bouma, BE TI Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting SO OPTICS EXPRESS LA English DT Article ID SPECTRAL INTERFEROMETRY; COHERENCE TOMOGRAPHY; REFLECTOMETRY; COMPONENTS; RESOLUTION; FIBER; LASER AB A novel technique using an acousto-optic frequency shifter in optical frequency domain imaging (OFDI) is presented. The frequency shift eliminates the ambiguity between positive and negative differential delays, effectively doubling the interferometric ranging depth while avoiding image cross-talk. A signal processing algorithm is demonstrated to accommodate nonlinearity in the tuning slope of the wavelength-swept OFDI laser source. (C)2004 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR-718, Boston, MA 02114 USA. EM syun@hms.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769-02, R33 CA110130, R01 CA103769, R33 CA110130-02]; NHLBI NIH HHS [R01 HL070039, R01 HL070039-02] NR 13 TC 121 Z9 121 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 4 PY 2004 VL 12 IS 20 BP 4822 EP 4828 DI 10.1364/OPEX.12.004822 PG 7 WC Optics SC Optics GA 859HL UT WOS:000224253900017 PM 19484034 ER PT J AU Menzaghi, C Ercolino, T Salvemini, L Coco, A Kim, SH Fini, G Doria, A Trischitta, V AF Menzaghi, C Ercolino, T Salvemini, L Coco, A Kim, SH Fini, G Doria, A Trischitta, V TI Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13 SO PHYSIOLOGICAL GENOMICS LA English DT Article DE insulin resistance; adipocytokines; heritability; haplotype-tagging single-nucleotide polymorphisms; linkage study ID INSULIN-RESISTANCE SYNDROME; ADIPOSE-SPECIFIC PROTEIN; PIMA INDIAN POPULATION; METABOLIC SYNDROME; LIPID-METABOLISM; LINKAGE ANALYSIS; OBESITY; GLUCOSE; POLYMORPHISM; ASSOCIATION AB Adiponectin is a circulating enhancer of insulin action that is secreted by the adipose tissue. In epidemiological studies, serum levels of this protein predict the risk of type 2 diabetes and cardiovascular events. Serum adiponectin levels have been associated with variants at the adiponectin (APM1) and PPARgamma2 loci and have also been linked to markers on 5p15 and 14q13. We investigated the role of these four loci in regulating serum adiponectin in a Caucasian population from Italy. Four haplotype-tagging single-nucleotide polymorphisms (ht-SNPs) (-11377 C>G, -4041 A>C, +45 T>G, and +276 G>T) at the APM1 locus and the PPARgamma2 Pro12Ala polymorphism were examined for association with serum adiponectin in 413 unrelated, nondiabetic individuals. Of the five SNPs tested, +276G>T was the only one to be associated with serum adiponectin (P = 0.032), with "TT" individuals having higher adiponectin levels than other subjects. In a variance-components analysis of 737 nondiabetic members of 264 nuclear families, adiponectin heritability was 30%, with a small but significant proportion explained by the +276 genotype (P = 0.0034). Suggestive evidence of linkage with adiponectin levels was observed on chromosome 14q13, with a LOD of 2.92 (P = 0.000057) after including the APM1 + 276 genotype in the model. No linkage was observed at 5p15. Our data indicate a strong genetic control of serum adiponectin. A small proportion of this can be attributed in our population to variability at the APM1 locus, but an as yet unidentified gene on 14q13 appears to play a much bigger role. C1 Sci Inst CSS, Unit Endocrinol, I-71013 San Giovanni Rotondo, FG, Italy. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Menzaghi, C (reprint author), Sci Inst CSS, Unit Endocrinol, Poliambulatoria Giovanni Paolo II,Viale Padre Pio, I-71013 San Giovanni Rotondo, FG, Italy. EM c.menzaghi@operapadrepio.it RI Trischitta, Vincenzo/K-1487-2016; Salvemini, Lucia/K-2121-2016 OI Menzaghi, Claudia/0000-0002-7438-8955; Trischitta, Vincenzo/0000-0003-1174-127X; Salvemini, Lucia/0000-0001-8776-9477 FU NHLBI NIH HHS [HL-73168] NR 23 TC 49 Z9 53 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT 4 PY 2004 VL 19 IS 2 BP 170 EP 174 DI 10.1152/physiolgenomics.00122.2004 PG 5 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 859JR UT WOS:000224259800003 PM 15252189 ER PT J AU Keim, SM Spaite, DW Malo, RF Garrison, HG Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR AF Keim, SM Spaite, DW Malo, RF Garrison, HG Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR TI Establishing the scope and methodological approach to out-of-hospital outcomes and effectiveness research SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE outcomes research; out-of-hospital medicine; emergency medical services research ID EMERGENCY MEDICAL-SERVICES; ADVANCED LIFE-SUPPORT; CARDIAC-ARREST SURVIVAL; SMALL-AREA VARIATIONS; HEALTH-CARE SERVICES; PROJECT; DEFIBRILLATION; TRAUMA; FUTURE; METAANALYSIS AB Outcomes research offers out-of-hospital medicine a valuable methodology for studying the effectiveness of services provided in the out-of hospital setting. A clear understanding of the history and constructs of outcomes research is necessary for its integration into emergency medical services research. This report describes the conceptual framework of outcomes research and key methodological considerations for the successful implementation of out-of-hospital outcomes research. Illustrations of the specific applications of outcomes research and implications to existing methodologies are given, as well as suggestions for improved interdisciplinary research. Key words: outcomes research; out-of-hospital medicine; emergency medical services research. C1 Univ Arizona, Dept Emergency Med, Emergency Med Res Ctr, Coll Med, Tucson, AZ 85724 USA. Univ Michigan, Med Ctr, Dept Emergency Med, Ann Arbor, MI USA. E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC USA. Massachusetts Gen Hosp, Pediat Emergency Serv, Boston, MA USA. Massachusetts Dept Publ Hlth, Emergency Med Serv Children, Boston, MA USA. Univ Ottawa, Div Emergency Med, Ottawa, ON, Canada. Univ Ottawa, Loeb Hlth Res Inst, Ottawa, ON, Canada. New York Med Coll, Inst Trauma & Emergency Care, Valhalla, NY USA. EMSSTAR Grp, Annapolis, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Hlth Span Transportat Serv, St Paul, MN USA. Allina Hlth Syst, St Paul, MN USA. RP Keim, SM (reprint author), Univ Arizona, Dept Emergency Med, Emergency Med Res Ctr, Coll Med, 1501 N Campbell, Tucson, AZ 85724 USA. EM sam@aemrc.arizona.edu OI Spaite, Daniel/0000-0003-2601-6476; Stiell, Ian/0000-0002-2583-6408 FU NHLBI NIH HHS [5K30HL004519-04] NR 54 TC 10 Z9 10 U1 0 U2 1 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 OCT PY 2004 VL 11 IS 10 BP 1067 EP 1073 DI 10.1197/j.aem.2004.04.014 PG 7 WC Emergency Medicine SC Emergency Medicine GA 861GW UT WOS:000224405100011 PM 15466150 ER PT J AU Keim, SM Spaite, DW Malo, RF Garrison, HG Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR AF Keim, SM Spaite, DW Malo, RF Garrison, HG Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR TI Risk adjustment and outcome measures for out-of-hospital respiratory distress SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE respiratory distress; outcomes; pulse oximetry; peak expiratory flow rate; visual analog dyspnea scale; mortality; out-of-hospital research; risk adjustment ID PEAK EXPIRATORY FLOW; EMERGENCY MEDICAL-SERVICES; OBSTRUCTIVE PULMONARY-DISEASE; LIFE-SUPPORT OPALS; PULSE OXIMETRY; MINI-WRIGHT; CARBON-DIOXIDE; CARDIAC-ARREST; SMALL AIRWAYS; CHILDREN AB The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work, this group delineated the priority conditions, described conceptual models, suggested core and risk adjustment measures potentially useful to emergency medical services research, and summarized out-of-hospital pain measurement. In this fifth article in the EMSOP series, the authors recommend specific risk-adjustment measures and outcome measures for use in out-of-hospital research on patients presenting with respiratory distress. The methodology included systematic literature searches and a structured review by an expert panel. The EMSOP group recommends use of pulse oximetry, peak expiratory flow rate, and the visual analog dyspnea scale as potential risk-adjustment measures and outcome measures for out-of-hospital research in patients with respiratory distress. Furthermore, using mortality as an outcome measure is also recommended. Future research is needed to alleviate the paucity of validated tools for out-of-hospital outcomes research. Key words: respiratory distress; outcomes; pulse oximetry; peak expiratory flow rate; visual analog dyspnea scale; mortality; out-of-hospital research; risk adjustment. C1 Univ Arizona, Dept Emergency Med, Coll Med, Arizona Emergency Med Res Ctr, Tucson, AZ 85724 USA. Univ Michigan, Med Ctr, Dept Emergency Med, Ann Arbor, MI USA. E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC USA. Massachusetts Gen Hosp, Pediat Emergency Serv, Boston, MA USA. Emergency Med Serv Children, Boston, MA USA. Massachusetts Dept Publ Hlth, Boston, MA USA. Univ Ottawa, Div Emergency Med, Ottawa, ON, Canada. Univ Ottawa, Loeb Hlth Res Inst, Ottawa, ON, Canada. New York Med Coll, Inst Trauma & Emergency Care, Valhalla, NY USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. EMSSTAR Grp, Annapolis, MD USA. HealthSpan Transportat Serv, St Paul, MN USA. Allina Hlth Syst, St Paul, MN USA. RP Keim, SM (reprint author), Univ Arizona, Dept Emergency Med, Coll Med, Arizona Emergency Med Res Ctr, 1501 N Campbell, Tucson, AZ 85724 USA. EM sam@aemrc.arizona.edu OI Spaite, Daniel/0000-0003-2601-6476; Stiell, Ian/0000-0002-2583-6408 NR 70 TC 10 Z9 11 U1 1 U2 1 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 OCT PY 2004 VL 11 IS 10 BP 1074 EP 1081 DI 10.1197/j.aem.2004.03.010 PG 8 WC Emergency Medicine SC Emergency Medicine GA 861GW UT WOS:000224405100012 PM 15466151 ER PT J AU vanSonnenberg, E AF vanSonnenberg, E TI Depressing? Heck no, uplifting! SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP vanSonnenberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2004 VL 11 IS 10 BP 1083 EP 1084 DI 10.1016/j.acra.2004.08.005 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 871DS UT WOS:000225110100001 PM 15530800 ER PT J AU Sanelli, PC Lev, MH Eastwood, JD Gonzalez, RG Lee, TY AF Sanelli, PC Lev, MH Eastwood, JD Gonzalez, RG Lee, TY TI The effect of varying user-selected input parameters on quantitative values in CT perfusion maps SO ACADEMIC RADIOLOGY LA English DT Article DE CT perfusion; quantitative analysis; acute stroke ID STROKE AB Rationale and Objectives. Deconvolution-based software can be used to calculate quantitative maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) from first-pass computed tomography perfusion (CTP) datasets. The application of this software requires the user to select multiple input variables. The purpose of this study was to investigate the degree to which both major and minor variations of these user-defined inputs would affect the final quantitative values of CBF, CBV, and MTT. Materials and Methods. A neuroradiologist constructed CBF, CBV, and MTT maps using standard methodology with commercially available software (GE Functool Version 1.9s) from CTP datasets of three acute stroke patients. Each map was reconstructed multiple times by systematically and independently varying the following parameters: postenhancement and preenhancement cutoff values, arterial and venous region-of-interest (ROI) placement, and arterial and venous ROI size. The resulting quantitative CTP values were compared using identical ROIs placed at the infarct core. Results. Major variations of either arterial ROI placement or arterial and venous ROI size had no significant effect on the mean CBF, CBV, and MTT values at the infarct core (p > .05). Even minor variations, however, in the choice of venous ROI placement or in pre- and postenhancement cutoff values significantly altered the quantitative values for each of the CTP maps, by as much as threefold. Conclusion. Even minor variations of user-defined inputs can significantly influence the quantitative, deconvolution-based CTP map values of acute stroke patients. Although quantitation was robust to the choice of arterial ROI placement and arterial or venous ROI size, it was strongly dependent on the choice of venous ROI location and pre- and postenhancement cut-off values. Awareness of these results by clinicians may be important in the creation of quantitatively accurate CTP maps. (C) AUR, 2004. C1 Cornell Univ, Dept Radiol, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. John P Robarts Res Inst, London, ON N6A 5K8, Canada. RP Sanelli, PC (reprint author), Cornell Univ, Dept Radiol, Weill Med Coll, New York Presbyterian Hosp, 520 E 68th St,Starr Pavil,Starr 630, New York, NY 10021 USA. EM pcs9001@med.cornell.edu RI Lee, Ting-Yim/M-1721-2013 NR 9 TC 79 Z9 82 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2004 VL 11 IS 10 BP 1085 EP 1092 DI 10.1016/j.acra.2004.07.002 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 871DS UT WOS:000225110100002 PM 15530801 ER PT J AU Johansen, KL AF Johansen, KL TI Treatment of hypogonadism in men with chronic kidney disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE testosterone; androgens; hypogonadism; chronic kidney disease; end-stage renal disease ID TESTOSTERONE TRANSDERMAL SYSTEM; CLINICAL-RESEARCH-CENTER; CORONARY-ARTERY-DISEASE; CHRONIC-RENAL-FAILURE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; RANDOMIZED CONTROLLED-TRIAL; PITUITARY-TESTICULAR AXIS; BONE-MINERAL DENSITY; NANDROLONE DECANOATE; REPLACEMENT THERAPY AB Hypogonadism is common among men with chronic kidney disease, but few studies have directly assessed the effects of testosterone replacement in this population. Limited information suggests that androgen replacement may improve libido and sexual function among men who are frankly hypogonadal. However, the threshold for normal sexual function is in the lower end of the normal range. Increasing serum testosterone above this level does not appear to have beneficial effects on sexual functioning. On the other hand, at least among healthy men, the dose-response curve for anabolic effects of testosterone administration appears to extend to testosterone levels on the high end of the normal range or above. Small studies have suggested that androgen treatment has anabolic effects among end-stage renal disease patients, even in the absence of hypogonadism. Androgens have potential side effects, and some preinitiation and subsequent assessment and monitoring are recommended to minimize these adverse effects. Recommendations for healthy older men appear to be reasonable for patients with chronic kidney disease. More research is needed to measure the effects of androgen therapy on various symptoms of hypogonadism as well as on overall quality of life, physical functioning, and survival among patients with chronic kidney disease. (C) 2004 by the National Kidney Foundation, Inc. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Div Nephrol, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM johanse@itsa.ucsf.edu NR 71 TC 14 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2004 VL 11 IS 4 BP 348 EP 356 DI 10.1053/j.ackd.2004.07.006 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 868FQ UT WOS:000224899900005 PM 15492971 ER PT J AU Meeker, RB Boles, JC Bragg, DC Robertson, K Hall, C AF Meeker, RB Boles, JC Bragg, DC Robertson, K Hall, C TI Development of neuronal sensitivity to toxins in cerebrospinal fluid from HIV-type 1-infected individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID FELINE IMMUNODEFICIENCY VIRUS; RAT HIPPOCAMPAL-NEURONS; AMINO-ACID RECEPTORS; PEDIATRIC-PATIENTS; CHOROID-PLEXUS; CALCIUM HOMEOSTASIS; NMDA RECEPTOR; COAT PROTEIN; VIRAL LOAD; CHILDREN AB HIV infection of the immature nervous system generally results in a rapid progression of neurological disease that cannot easily be explained by the severity of encephalitis, viral burden, systemic immune deficiency, or developmental changes in utero. Rather than the viral infection dictating disease progression, we explored the possibility that immature neurons might be particularly sensitive to toxins secreted in response to HIV. Primary cultures of rat cortical neurons were exposed to toxic cerebrospinal fluid (CSF) from HIV-infected individuals (CSFtox) and evaluated for changes in intracellular calcium and cell death. CSFtox had no detectable effect on early neurite outgrowth, calcium regulation, or cell death during the first few days in culture. Starting at Day 4, delayed increases in intracellular calcium appeared in response to CSFtox. The magnitude of the delayed calcium rise and cell death increased with the age of the culture and correlated with the appearance of synaptophysin immunoreactive varicosities. A similar gradual development of sensitivity was seen during exposure of feline neurons to toxins generated by choroid plexus macrophages after exposure to feline immunodeficiency virus. The possibility that toxin sensitivity is dependent on the presence of synaptic activity is consistent with the rapid pathogenesis in the CNS seen during the first postnatal year. Emerging synaptic activity coupled with other factors such as high metabolic demand in the young nervous system may combine to increase the likelihood of calcium overload and neuronal dysfunction in response to HIV-associated toxins. C1 Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Program Neurosci, Charlestown, MA 02129 USA. RP Meeker, RB (reprint author), Univ N Carolina, Dept Neurol, CB 7025,6109F Neurosci Res Bldg, Chapel Hill, NC 27599 USA. EM meekerr@glial.med.unc.edu FU NIAID NIH HHS [AI47749]; NICHD NIH HHS [P30-HD37260]; NIMH NIH HHS [MH62690] NR 34 TC 5 Z9 6 U1 1 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2004 VL 20 IS 10 BP 1072 EP 1086 DI 10.1089/aid.2004.20.1072 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 863FR UT WOS:000224546900006 PM 15585098 ER PT J AU Brennan, FX Stromberg, MF AF Brennan, FX Stromberg, MF TI Ethanol consumption improves avoidance learning in rats: role of deprivation interval SO ALCOHOL LA English DT Article DE ethanol; escape/avoidance; rats; stress ID RESPONSE-INDEPENDENT COCAINE; NUCLEUS-ACCUMBENS; ALCOHOL; STRESS; PERFORMANCE; REDUCTION; MICE; REINFORCEMENT; PREFERENCE; INCREASES AB Voluntary oral self-administration of ethanol in rats has been used to model ethanol consumption and abuse in human beings, with contradictory results. The purpose of the current study was to assess the effect of voluntary ethanol consumption on acquisition of a lever press escape/avoidance task in rats. Male Wistar rats were exposed to ethanol in a limited-access procedure, and either 1 day or 10 days after their last ethanol exposure, animals received a 4-h lever press escape/avoidance session. Control animals were not exposed to ethanol at any time. Animals in the 1-day ethanol-deprivation group performed significantly better than did the other two groups with respect to avoidance responding. There were no group differences in number of lever presses during a safety period, a measure of anxiety. Further, we obtained a significant negative correlation between behavioral performance and change in ethanol consumption after the escape/avoidance session, as well as a significant positive correlation between baseline ethanol consumption and avoidance performance. Results are discussed in terms of the potential neural mediators of the improved avoidance effect in animals in the 1-day ethanol-deprivation group. (c) 2005 Elsevier Inc. All rights reserved. C1 Philadelphia VA Med Ctr, Med Res Serv 151, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA. RP Brennan, FX (reprint author), Philadelphia VA Med Ctr, Med Res Serv 151, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Brennan_F@mail.trc.upenn.edu FU NIAAA NIH HHS [AA-00228] NR 28 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD OCT-NOV PY 2004 VL 34 IS 2-3 BP 159 EP 164 DI 10.1016/j.alcohol.2004.07.011 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 908BO UT WOS:000227762400008 PM 15902909 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Trials on reflux disease - the role of acid secretion and inhibition SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Symposium on Critical Evidence on Gastric Acid Reflux and Barretts Oesophagus CY 2003 CL Marbella, SPAIN ID HELICOBACTER-PYLORI INFECTION; RANDOMIZED CONTROLLED-TRIAL; GASTROESOPHAGEAL-REFLUX; GASTRIC-ACID; EROSIVE ESOPHAGITIS; APPROPRIATE CONTROLS; BARRETTS-ESOPHAGUS; SYMPTOM RELIEF; CORPUS GASTRITIS; PEPSIN-SECRETION AB The importance of gastric acid in the pathophysiology of gastro-oesophageal reflux disease is substantiated by the extraordinary therapeutic success of acid inhibition in the management of the disease. The influence of many risk factors for gastro-oesophageal reflux disease is also mediated through their effect on gastric acid secretion and acid reflux. Helicobacter pylori reduces the risk of gastro-oesophageal reflux disease by causing corpus gastritis and reducing gastric acid output. The geographical and temporal trends of H. pylori infection in human populations and its influence on gastric acid secretion are responsible for much of the apparent epidemiology of gastro-oesophageal reflux disease. On average, intra-oesophageal exposure to acid is higher in patients who respond poorly to antisecretory medication. It also tends to increase with increasing severity of reflux disease. However, gastric acid secretion and intra-oesophageal acid exposure vary markedly in reflux patients. The degrees of gastric or intra-oesophageal acidity do not allow the prediction of the presence or severity of gastro-oesophageal reflux disease in the individual subject. The many clinical trials on gastro-oesophageal reflux disease indicate that the reflux of gastric acid constitutes an essential mechanism in the development of this disease, but that additional and partly unknown risk factors must contribute to its aetiology and promote its occurrence in the individual patient. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 41 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT PY 2004 VL 20 SU 5 BP 2 EP 8 DI 10.1111/j.1365-2036.2004.02131.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 858CH UT WOS:000224167300002 PM 15456457 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Anti-reflux surgery and endoluminal therapies SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Symposium on Critical Evidence on Gastric Acid Reflux and Barretts Oesophagus CY 2003 CL Marbella, SPAIN ID GASTROESOPHAGEAL-REFLUX DISEASE; LAPAROSCOPIC NISSEN FUNDOPLICATION; BARRETTS-ESOPHAGUS; FOLLOW-UP; TOUPET FUNDOPLICATION; RADIOFREQUENCY ENERGY; SURGICAL THERAPY; CONTROLLED TRIAL; GERD; ADENOCARCINOMA AB In the short term, fundoplication and antisecretory medication are equally effective in the management of gastro-oesophageal reflux disease. However, over the long term, the fundoplication wrap tends to become loose, and many surgical patients continue to take antisecretory medication after surgery. The operation is technically complex and takes a long time to learn. Inexperience of the individual surgeon is a major factor contributing to the occurrence of postsurgical complications. Fundoplication does not prevent the occurrence of Barrett's oesophagus nor its progression to oesophageal adenocarcinoma. There is no evidence to suggest that the procedure is less costly or more cost-effective than long-term maintenance therapy with antisecretory medications, especially if surgical failures and postsurgical complications are taken into account. Fundoplication represents an alternative to medical therapy in patients with gastro-oesophageal reflux disease who cannot or do not want to be on long-term maintenance therapy with antisecretory medication. Endoluminal procedures, such as radiofrequency ablation, endoscopic suturing and injection at the gastro-oesophageal junction, work only in mild forms of reflux disease. They fail to provide complete relief of reflux symptoms and do not heal erosive oesophagitis. All endoluminal procedures would have to undergo major technological improvements before they could become comparable with fundoplication or antisecretory therapy. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 34 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT PY 2004 VL 20 SU 5 BP 81 EP 88 DI 10.1111/j.1365-2036.2004.02130.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 858CH UT WOS:000224167300014 PM 15456469 ER PT J AU Ezekiel, F Chao, L Kornak, J Du, AT Cardenas, V Truran, D Jagust, W Chui, H Miller, B Yaffe, K Schuff, N Weiner, M AF Ezekiel, F Chao, L Kornak, J Du, AT Cardenas, V Truran, D Jagust, W Chui, H Miller, B Yaffe, K Schuff, N Weiner, M TI Comparisons between global and focal brain atrophy rates in normal aging and Alzheimer disease boundary shift integral versus tracing of the entorhinal cortex and hippocampus SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; boundary shift integral; serial MRI; longitudinal; normal aging; Alzheimer disease ID COGNITIVE IMPAIRMENT; MRI; AD; PROGRESSION; VOLUMETRY; DEMENTIA; DECLINE AB The objectives of this study were to (1) compare atrophy rates associated with normal aging and Alzheimer disease (AD) using the semi-automated Boundary Shift Integral (BSI) method and manual tracing of the entorhinal cortex (ERC) and hippocampus and (2) calculate power of BSI vs. ERC and hippocampal volume changes for clinical trials in AD. We quantified whole brain and ventricular BSI atrophy rates and ERC and hippocampal atrophy rates from longitudinal MRI data in 20 AD patients and 22 age-matched healthy controls. All methods revealed significant brain atrophy in controls and AD patients. AD patients had approximately 2.5 times greater whole brain BSI atrophy rates and more than 5 times greater ERC and hippocampal atrophy rates than controls. ERC and hippocampal atrophy rates were higher in both groups than whole brain BSI atrophy rates, but lower than ventricular BSI atrophy rates. Effect size and power calculations suggest that ERC and hippocampal measurements may be more sensitive than ventricular or whole brain BSI for detecting AD progression and the potential effects of disease modifying agents. Logistic regression analysis revealed that combined rates of ERC and ventricular BSI were the best explanatory variables for classifying AD from controls. C1 San Francisco VA Med Ctr, Magnet Resonance Unit, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. 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 Berkeley, Inst Neurosci, Berkeley, CA 94720 USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. RP Weiner, M (reprint author), San Francisco VA Med Ctr, Magnet Resonance Unit, 114M,4150 Clement St, San Francisco, CA 94121 USA. EM mweiner@itsa.ucsf.edu FU NIA NIH HHS [R01 AG10897, R01 AG010897, P50 AG023501, P01 AG12435, P01 AG012435] NR 28 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2004 VL 18 IS 4 BP 196 EP 201 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 882HM UT WOS:000225930000008 PM 15592130 ER PT J AU Graham, DP Cully, JA Snow, AL Massman, P Doody, R AF Graham, DP Cully, JA Snow, AL Massman, P Doody, R TI The Alzheimer's disease assessment scale - Cognitive subscale - Normative data for older adult controls SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; assessment; dementia ID PERFORMANCE; POPULATION; PREDICTORS; EDUCATION; VALIDITY; TRIALS AB The Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog) is commonly used to assess cognitive dysfunction in individuals with Alzheimer disease and other dementias. The purpose of this study was to provide non-native scores for the ADAS-cog 11 individual items and total score, as well for delayed recall errors, using normal, elderly volunteers. The ADAS-cog was administered to 124, non-cognitively impaired volunteers ages 55 to 89, with 10 to 21 years of education. The mean total ADAS-cog score was five. The ADAS-cog error score was not associated with education in this highly educated group, and was positively correlated (P < 0.001) with the age of the participant. Age stratified ADAS-cog normative data are reported for the ADAS-cog total and the delayed recall error score. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Ultizat Studies Hlth Serv, Houston, TX 77030 USA. Baylor Coll Med, Vet Affairs S Cent MIRECC, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. Baylor Coll Med, Rush Alzheimers Dis Ctr, Houston, TX 77030 USA. RP Graham, DP (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Ultizat Studies Hlth Serv, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM david.graham@med.va.gov RI Graham, David /J-1158-2014 FU NIA NIH HHS [AGO P50 8664] NR 27 TC 24 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2004 VL 18 IS 4 BP 236 EP 240 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 882HM UT WOS:000225930000015 PM 15592137 ER PT J AU Casella, G Leibig, M Schiele, TM Schrepf, R Seelig, V Stempfle, HU Erdin, P Rieber, J Konig, A Siebert, U Klauss, V AF Casella, G Leibig, M Schiele, TM Schrepf, R Seelig, V Stempfle, HU Erdin, P Rieber, J Konig, A Siebert, U Klauss, V TI Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve? SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY PRESSURE; VELOCITY RESERVE; BLOOD-FLOW; 5'-TRIPHOSPHATE; PAPAVERINE; SEVERITY; STENOSIS; HUMANS; INDEX AB Background Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared With intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. Methods FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 mug as boli), and a standard intravenous infusion of 140 mug/kg/min were administered in a randomized fashion. Results. Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-mug intracoronary bolus and 140-mug/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-mug bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-mug intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. Conclusions This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 mug. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 mug/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR. C1 Univ Munich, Klinikum Innenstadt, Med Poliklin, Dept Cardiol, D-8000 Munich, Germany. Osped Maggiore Bologna, Dept Cardiol, Bologna, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Casella, G (reprint author), Via Milani 8, I-40026 Imola, Bo, Italy. EM gcas@fastmail.it NR 19 TC 59 Z9 60 U1 1 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 OCT PY 2004 VL 148 IS 4 BP 590 EP 595 DI 10.1016/j.ahj.2004.04.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864RP UT WOS:000224650900007 PM 15459587 ER PT J AU Kathiresan, S Servoss, SJ Newell, JB Trani, D MacGillivray, TE Lewandrowski, K Lee-Lewandrowski, E Januzzi, JL AF Kathiresan, S Servoss, SJ Newell, JB Trani, D MacGillivray, TE Lewandrowski, K Lee-Lewandrowski, E Januzzi, JL TI Cardiac troponin T elevation after coronary artery bypass grafting is associated with increased one year mortality SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CREATINE KINASE-MB; MYOCARDIAL-INFARCTION; SURGERY; INTERVENTION; ATHERECTOMY; DAMAGE AB The results of the present study extend the value of assessing troponin T for the prediction of mortality rate 1 year after coronary artery bypass grafting; this study supports previous work that demonstrated the value of postoperative assessment of troponin T for the prediction of in-hospital adverse outcome after coronary artery bypass grafting. (C) 2004 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA USA. Massachusetts Gen Hosp, Clin Chem Lab, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 019,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 15 TC 49 Z9 49 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 OCT 1 PY 2004 VL 94 IS 7 BP 879 EP 881 DI 10.1016/j.amjcard.2004.06.022 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 858VO UT WOS:000224220400007 PM 15464669 ER PT J AU Lopez-Garcia, E Schulze, MB Fung, TT Meigs, JB Rifai, N Manson, JE Hu, FB AF Lopez-Garcia, E Schulze, MB Fung, TT Meigs, JB Rifai, N Manson, JE Hu, FB TI Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary patterns; inflammation; endothelial; dysfunction; women; C-reactive protein ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; FOOD-FREQUENCY QUESTIONNAIRE; TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; RISK; MEN; ATHEROSCLEROSIS; REPRODUCIBILITY; MORTALITY AB Background: Endothelial dysfunction is one of the mechanisms linking diet and the risk of cardiovascular disease. Objective: We evaluated the hypothesis that dietary patterns (summary measures of food consumption) are directly associated with markers of inflammation and endothelial dysfunction, particularly C-reactive protein (CRP), interleukin 6, E-selectin, soluble intercellular adhesion molecule I (sICAM-1), and soluble vascular cell adhesion molecule I (sVCAM-1). Design: We conducted a cross-sectional study of 732 women from the Nurses' Health Study I cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and diabetes mellitus at the time of blood drawing in 1990. Dietary intake was documented by using a validated food-frequency questionnaire in 1986 and 1990. Dietary patterns were generated by using factor analysis. Results: A prudent pattern was characterized by higher intakes of fruit, vegetables, legumes, fish, poultry, and whole grains, and a Western pattern was characterized by higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains. The prudent pattern was inversely associated with plasma concentrations of CRP (P = 0.02) and E-selectin (P = 0.001) after adjustment for age, body mass index (BMI), physical activity, smoking status, and alcohol consumption. The Western pattern showed a positive relation with CRP (P < 0.001), interleukin 6 (P = 0.006), E-selectin (P < 0.001), sICAM-1 (P < 0.001), and sVCAM-1 (P = 0.008) after adjustment for all confounders except BMI; with further adjustment for BMI, the coefficients remained significant for CRP (P = 0.02), E-selectin (P < 0.001), sICAM-1 (P = 0.002), and sVCAM-1 (P = 0.02). Conclusion: Because endothelial dysfunction is an early step in the development of atherosclerosis, this study suggests a mechanism for the role of dietary patterns in the pathogenesis of cardiovascular disease. 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 Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Simmons Coll, Nutr Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. RP Lopez-Garcia, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM elopezga@hsph.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK55523, DK58845] NR 32 TC 351 Z9 357 U1 5 U2 38 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2004 VL 80 IS 4 BP 1029 EP 1035 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 856VI UT WOS:000224073000035 PM 15447916 ER PT J AU McCollum, AD Kulke, MH Ryan, DP Clark, JW Shulman, LN Mayer, RJ Bartel, S Fuchs, CS AF McCollum, AD Kulke, MH Ryan, DP Clark, JW Shulman, LN Mayer, RJ Bartel, S Fuchs, CS TI Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE pancreatic endocrine tumor; islet cell carcinoma; streptozocin; chemotherapy ID ISLET-CELL CARCINOMA; MEDICAL ONCOLOGY GROUP; NEUROENDOCRINE TUMORS; ITALIAN TRIALS; FLUOROURACIL; OCTREOTIDE AB Background: The combination of streptozocin and doxorubicin has been considered the standard palliative chemotherapy regimen in patients with advanced pancreatic endocrine tumors (PETs). However, a recent review failed to confirm high antitumor activity in patients with advanced PETs. Methods: We retrospectively reviewed the records of 16 consecutive patients who received streptozocin and doxorubicin for advanced PETs at Dana Farber/Partners Cancer Care institutions. Baseline patient characteristics, radiographic response to therapy, treatment-related toxicity, progression-free and overall survival were analyzed. Results: One patient demonstrated an objective partial response to therapy (objective response rate [ORR], 6%; 95% confidence interval [Cl],. 0-18%). Six patients achieved stable disease (38%; 95% Cl. 14-62%) and 9 patients demonstrated disease progression on initial restaging (56%, 95% Cl, 33-77%). The median progression-free survival and overall survival were 3.9 months (95% Cl, 2.8-8.8) and 20.2 months (95% Cl, 9.7-37.4), respectively. Conclusions: In this retrospective cohort, the combination of streptozocin and doxorubicin failed to demonstrate substantial antitumor activity in patients with advanced PET. Our findings underscore the need for new therapeutic options in this patient Population. C1 Baylor Univ, Charles A Sammons Canc Ctr, Med Ctr, Dallas, TX 75246 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP McCollum, AD (reprint author), Baylor Univ, Charles A Sammons Canc Ctr, Med Ctr, 3535 Worth St,Suite 240, Dallas, TX 75246 USA. EM mccollum@usoncology.com NR 13 TC 75 Z9 77 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2004 VL 27 IS 5 BP 485 EP 488 DI 10.1097/01.coc.0000135343.06038.eb PG 4 WC Oncology SC Oncology GA 860JC UT WOS:000224337500011 PM 15596916 ER PT J AU Beer, TM Garzotto, M Katovic, NM AF Beer, TM Garzotto, M Katovic, NM TI High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE prostate cancer; chemotherapy; carboplatin; calcitriol; vitamin D ID SQUAMOUS-CELL CARCINOMA; VITAMIN-D ANALOGS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; ANTITUMOR-ACTIVITY; PLATINUM DRUGS; IN-VITRO; HUMAN KERATINOCYTES; OVARIAN-CARCINOMA; CLINICAL-TRIALS AB Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 mug/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI greater than or equal to 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Mail Code L586,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCRR NIH HHS [3M01RR00334-33S2] NR 60 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2004 VL 27 IS 5 BP 535 EP 541 DI 10.1097/01.coc.0000136020.27904.9c PG 7 WC Oncology SC Oncology GA 860JC UT WOS:000224337500021 PM 15596926 ER PT J AU Thomas, SH Winsor, GR Pang, PS Driscoll, KA Parry, BA AF Thomas, SH Winsor, GR Pang, PS Driscoll, KA Parry, BA TI Use of a radial artery compression device for noninvasive, near-continuous blood pressure monitoring in the ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL Boston, MA SP Amer Coll Emergency Physicians DE noninvasive monitoring; mean arterial blood pressure; hemodynamic monitoring; radial artery ID HEMODYNAMIC SUPPORT; PRACTICE PARAMETERS AB This study's goal was to test a novel device using continuous partial radial artery compression for mean arterial pressure (MAP) measurement. A prospective, nonblind, convenience-sample trial at a level I center (annual ED census 70,000) enrolled 15 adults with indwelling radial arterial catheters and accessible contralateral radial pulse. Subjects had MAPs measured simultaneously by test device (TEST assessments), oscillometric brachial artery cuff (OSC), and arterial line (ART). There was no difference between the three groups' MAP means (P = .98). R-2 values for ART/OSC and ART/TEST were 0.96 and 0.95, respectively (P < .001). TEST and OSC MAP readings were equally likely (P = 0.66) to be within 5 mm Hg of ART in both the overall set of 307 MAPs and in the subset of 120 cases in which ART MAN were below 80 (P = .47). The TEST device performed at least as well as oscillometric assessment, offering advantages of noninvasive, near-continuous data. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Boston MedFlight, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 115,55 Fruit St, Boston, MA 02114 USA. EM thomas.stephen@mgh.harvard.edu NR 12 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2004 VL 22 IS 6 BP 474 EP 478 DI 10.1016/j.ajem.2004.07.027 PG 5 WC Emergency Medicine SC Emergency Medicine GA 872TH UT WOS:000225230900007 PM 15520942 ER PT J AU Fang, M Lew, E Klein, M Sebo, T Su, YY Goyal, R AF Fang, M Lew, E Klein, M Sebo, T Su, YY Goyal, R TI DNA abnormalities as marker of risk for progression of Barrett's esophagus to adenocarcinoma: Image cytometric DNA analysis in formalin-fixed tissues SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HIGH-GRADE DYSPLASIA; FLOW-CYTOMETRY; FOLLOW-UP; ENDOSCOPIC SURVEILLANCE; GASTROESOPHAGEAL REFLUX; OBSERVER VARIATION; PREDICTIVE MARKER; CANCER; MALIGNANCY; DIAGNOSIS AB OBJECTIVES: To examine DNA content abnormalities in patients with Barrett's esophagus (BE) who progress to esophageal adenocarcinoma, using image cytometric DNA analysis (ICDA) of formalin-fixed tissues. METHODS: Studies were performed on archived biopsies of BE patients' undergoing endoscopic surveillance before developing adenocarcinoma. A comparison group consisted of BE patients' free of cancer during a follow-up period of over 9 yr. Tissue sections were analyzed for the degree of dysplasia and for DNA content abnormalities, using image cytometry. Additional patients were also analyzed in a cross-sectional study of 56 BE cases with and without dysplasia, including 12 cases of adenocarcinoma. RESULTS: Five patients developed adenocarcinoma during follow-up and earlier biopsies obtained before cancer diagnosis showed specialized intestinal metaplasia (SIM) followed by low-grade dysplasia (LGD) in one, SIM followed by high-grade dysplasia (HGD) in one, LGD in two, and HGD in one case. All five showed some DNA abnormality at baseline or in interval biopsies. In the comparison group, five of seven patients showed normal diploid DNA at baseline and on follow-up biopsies. One patient initially had diploid DNA, but developed aneuploidy 11 yr later. Another case initially had aneuploidy, but was diploid on follow-up. Overall, DNA abnormalities were found in 13% of cases with SIM without dysplasia, 60% with LGD, 73% with HGD, and 100% with adenocarcinoma. CONCLUSIONS: (i) Image cytometric DNA analysis is a useful method to examine DNA abnormalities in formalin-fixed tissues and may be more sensitive in predicting progression to adenocarcinoma than HGD. (ii) Histological dysplasia of any grade and DNA abnormalities, help identify BE patients at high risk for adenocarcinoma. C1 VA Boston Healthcare Syst, Ctr Swollowing & Motil Disorders, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. VA Med Ctr Providence RI, Dept Pathol, Providence, RI USA. Brown Med Sch, Providence, RI USA. Mayo Clin, Dept Pathol, Rochester, MN USA. RP Goyal, R (reprint author), VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIDDK NIH HHS [DK 031092] NR 40 TC 43 Z9 44 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 BP 1887 EP 1894 DI 10.1111/j.1572-0241.2004.30886.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861GK UT WOS:000224403900012 PM 15447746 ER PT J AU Isomoto, H Mukae, H Ishimoto, H Date, Y Nishi, Y Inoue, K Wada, A Hirayama, T Nakazato, M Kohno, S AF Isomoto, H Mukae, H Ishimoto, H Date, Y Nishi, Y Inoue, K Wada, A Hirayama, T Nakazato, M Kohno, S TI Elevated concentrations of alpha-defensins in gastric juice of patients with Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HUMAN NEUTROPHIL PEPTIDES; LEUKOCYTE GRANULE PROTEINS; HUMAN BETA-DEFENSIN-2; IMMUNE-RESPONSES; EPITHELIAL-CELLS; KAPPA-B; PLASMA; INTERLEUKIN-8; AMOXICILLIN; EXPRESSION AB OBJECTIVE: Defensins (alpha- and beta-defensins) are endogenous antimicrobial peptides. Little is known about alpha-defensins during Helicobacter pylori infection. METHODS: The concentrations of human neutrophil peptides (HNP-1, -2, and -3), the major components of neutrophils-derived alpha-defensins, were measured by radioimmunoassay (RIA) in plasma and gastric juice of 61 H. pylori-infected and 33 uninfected subjects, and before and after anti-H. pylori treatment in 12 patients with H. pylori-associated gastritis. Interleukin (IL)-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay. Histological grades of gastritis and neutrophil counts (/mm(2)) infiltrating in the gastric mucosa were determined using two biopsy specimens taken from the antrum and corpus. Immunohistochemistry and reverse-phase high performance liquid chromatography (RP-HPLC) were used to identify HNPs 1-3. RESULTS: HNP 1-3 concentrations in gastric juice were significantly higher in H. pylori-positive than in H. pylori-negative patients and significantly decreased after cure. HNP 1-3 concentrations in gastric juice correlated with IL-8 levels and neutrophil densities in the gastric mucosa and were associated with histological degree of gastritis, especially the grades of activity. Intense immunoreactivity for anti-HNPs 1-3 antiserum was noted in infiltrating neutrophils in H. pylori-infected mucosa. In RP-HPLC analysis, all of the HNP 1-3 molecules were identified as their mature forms. Plasma HNP 1-3 concentrations were similar in H. pylori-infected and non-infected groups and showed no correlations with other parameters. CONCLUSIONS: We demonstrated significantly elevated levels of HNPs 1-3 in gastric juice during H. pylori infection. The elevation of HNPs is presumably secondary to H.pylori-associated gastric inflammation involving neutrophil infiltration. C1 Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 852, Japan. Miyazaki Med Coll, Dept Internal Med 3, Miyazaki 88916, Japan. Nagasaki Univ, Sch Med, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. Shunkaikai Inoue Hosp, Nagasaki, Japan. RP Isomoto, H (reprint author), Harvard Univ, Sch Med, Dept Med,Gastrointestinal Unit, Massachusetts Gen Hosp, Jackson 706,55 Fruit St, Boston, MA 02114 USA. NR 37 TC 16 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 BP 1916 EP 1923 DI 10.1111/j.1572-0241.2004.40334.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861GK UT WOS:000224403900016 PM 15447750 ER PT J AU Sarkar, S Thompson, DG Woolf, CJ Hobson, AR Millane, T Aziz, Q AF Sarkar, S Thompson, DG Woolf, CJ Hobson, AR Millane, T Aziz, Q TI Patients with chest pain and occult gastroesophageal reflux demonstrate visceral pain hypersensitivity which may be partially responsive to acid suppression SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SECONDARY HYPERALGESIA; CENTRAL SENSITIZATION; CENTRAL MECHANISMS; ESOPHAGEAL PH; HUMANS; PLASTICITY; GENERATION; ACTIVATION; INDUCTION; SYMPTOMS AB OBJECTIVES: Mechanisms of chest pain in gastroesophageal reflux disease (GERD) are poorly understood. The recent demonstration in healthy subjects that lower esophageal acid exposure induces pain hypersensitivity within the nonacid-exposed upper esophagus (secondary allodynia) raises the possibility that an increase in spinal neuronal excitability (i.e., central sensitization) contributes to chest pain in GERD. The aim of this study was to determine whether in patients with unexplained chest pain, acid reflux contributes to esophageal pain hypersensitivity. METHODS: In 14 patients with chest pain and GERD and 8 healthy volunteers, electrical pain thresholds (PT) were recorded from the upper esophagus before, and then repeatedly for 90 min after either hydrochloric acid (0.15 M) or saline (0.15 M) infusion into the lower esophagus. Six patients underwent a repeat study after 6 wk of high-dose proton pump inhibitor (PPI) therapy. RESULTS: GERD patients had lower resting upper esophageal PT than in healthy subjects (40.8 +/- 9 mA and 70.4 +/- 11 mA, respectively; p = 0.018). Acid infusion reduced PT in the non-acid-exposed upper esophagus in healthy subjects, but not in the patients (area under curve [AUC] - 304 +/- 333 and 786 +/- 464; p = 0.03, respectively). Following PPI therapy, resting PT increased (34.65 +/- 13.4 to 40.5 +/- 12.5 mA; p = 0.03), and a reduction in PT now occurred in acid infusion (AUC - 369 +/- 321; p = 0.03). CONCLUSIONS: Patients with unexplained chest pain and occult GERD have esophageal pain hypersensitivity that is PPI responsive. The increase in resting PT and secondary allodynia only following PPI therapy suggests that pain hypersensitivity in these GERD patients may partially be the result of central sensitization. C1 Univ Manchester, Hope Hosp, Dept GI Sci, Salford M6 8HD, Lancs, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Univ S Manchester, Reg NW Cardiothorac Unit, Wythenshawe Hosp, Manchester, Lancs, England. RP Sarkar, S (reprint author), Univ Salford, Hope Hosp, Dept Gastroenterol, Clin Sci Bldg, Salford M6 8HD, Lancs, England. NR 35 TC 46 Z9 53 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 BP 1998 EP 2006 DI 10.1111/j.1572-0241.2004-40174.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861GK UT WOS:000224403900029 PM 15447763 ER PT J AU Fogt, F Brown, CA Badizadegan, K Zimmerman, RL Odze, R AF Fogt, F Brown, CA Badizadegan, K Zimmerman, RL Odze, R TI Low prevalence of loss of heterozygosity and SMAD4 mutations in sporadic and familial juvenile polyposis syndrome-associated juvenile polyps SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHILDHOOD; COMMON; TRACT AB BACKGROUND: Juvenile polyps (JP) may develop sporadically or may be associated with the familial juvenile polyposis syndrome (FJPS). In FJPS, the epithelium is susceptible to dysplasia and, ultimately adenocarcinoma. However, the mechanisms involved in this transformation are unknown. Since the epithelium in colorectal carcinogenesis undergoes a stepwise genetic progression, the purpose of this study was to determine if loss of heterozygosity (LOH) abnormalities can aid in the differentiation between sporadic and FJPS-associated polyps. DESIGN: Ninety-one routinely-processed JP from three groups of patients were evaluated for this study. Group 1 included 39 polyps from 39 patients with a single JP and no personal or family history of FJPS; group 2 consisted of 24 polyps from 15 patients with 2-5 JP and no history of FJPS; and group 3 included 29 polyps from 22 patients with >5 polyps either with (7) or without (15) a family history of FJPS. Epithelium from typical, atypical, and overtly dysplastic polyps, when present (2 cases in group 3 only), were evaluated separately by microdissection and PCR analysis for LOH of APC, p53, 3p, 9p, and mutations in exon 9 of the SMAD4 gene. RESULTS: SMAD4 mutations were observed in 3 polyps from 2 patients in group 3 (10% of informative cases; p < 0.05 vs group 1), but not in any of the polyps from the other two groups. Overall, LOH of APC, p53, 3p, and 9p were detected in 1%, 15%, 10%, and 4% of JPs, but no differences were observed between the three clinical groups. Two polyps, both in group 3, with definite dysplasia did not show any genetic alterations. The morphologic appearance of the polyps was not a reliable feature in helping to differentiate sporadic from FJPS-associated polyps. CONCLUSIONS: LOH of APC, p53, 3p, and 9p may not be involved in the carcinogenic pathway of FJPS-associated polyps. SMAD4 gene mutations show a low sensitivity but a high specificity for FJPS. C1 Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Lab Corp Amer, Ctr Mol Biol & Pathol, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Markets St, Philadelphia, PA 19104 USA. NR 22 TC 5 Z9 6 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 BP 2025 EP 2031 DI 10.1111/j.1572-0241.2004.30502.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861GK UT WOS:000224403900033 PM 15447767 ER PT J AU Bounds, BC Brugge, WR Kelsey, PB AF Bounds, BC Brugge, WR Kelsey, PB TI The DAVE project (digital atlas of video education): A new internet based digital video atlas for educational purposes SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 929 BP S304 EP S304 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700923 ER PT J AU Faigel, DO Sonnenberg, A Lieberman, DA AF Faigel, DO Sonnenberg, A Lieberman, DA TI Virtual Colonoscopy is not safer: Procedure- and screening program-related mortality of colonoscopy versus CT colonography SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 978 BP S322 EP S322 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700972 ER PT J AU Merrifield, BF Thompson, CC Kaplan, LM AF Merrifield, BF Thompson, CC Kaplan, LM TI Incapacity for physical activity limits weight loss after Roux-en-Y gastric bypass SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 758 BP S246 EP S246 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700752 ER PT J AU Pisegna, JR Karlstadt, RG Oh, D Graepel, J Dorr, MB AF Pisegna, JR Karlstadt, RG Oh, D Graepel, J Dorr, MB TI Preoperative IV pantoprazole (IVP) decreases gastric volume (GV) and acid output (GAO) and increases pH in elective surgery patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Wyeth Pharmaceut, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 118 BP S40 EP S40 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700118 ER PT J AU Qureshi, W Willingham, F Anand, BS AF Qureshi, W Willingham, F Anand, BS TI Localizing the lesion by capsule endoscopy: Newer techniques in improving accuracy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 202 BP S67 EP S67 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700202 ER PT J AU Sands, BE Sandborn, WJ Wolf, DC Katz, S Safdi, M Schwartz, DA Hanauer, SB AF Sands, BE Sandborn, WJ Wolf, DC Katz, S Safdi, M Schwartz, DA Hanauer, SB TI Pilot study on the safety and efficacy of granulocyte/monocyte adsorption apheresis with adacolumn in patients with inflammatory bowel disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Massachusetts Gen Hosp, Boston, MA USA. Mayo Clin, Rochester, MN USA. Atlanta GI Associates, Atlanta, GA USA. Long Isl Res Associates, Great Neck, NY USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 811 BP S263 EP S264 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700805 ER PT J AU Sands, BE Kozarek, R Spainhour, J Barish, C Becker, S Goldberg, L Katz, S Hogge, GS Harrigan, R Hanauer, S AF Sands, BE Kozarek, R Spainhour, J Barish, C Becker, S Goldberg, L Katz, S Hogge, GS Harrigan, R Hanauer, S TI Safety and efficacy of natalizumab in patients concurrently receiving infliximab in a phase 2 study of active Crohn's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 789 BP S256 EP S256 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700783 ER PT J AU Shih, AV Hur, C Gazelle, GS Zalis, ME Beinfeld, MT Podolsky, DK AF Shih, AV Hur, C Gazelle, GS Zalis, ME Beinfeld, MT Podolsky, DK TI The potential economic impact of computed tomographic colonography SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Gastroentrology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroentrol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2004 VL 99 IS 10 SU S MA 709 BP S229 EP S230 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 862GW UT WOS:000224479700703 ER PT J AU Paschou, P Feng, Y Pakstis, AJ Speed, WC DeMille, MM Kidd, JR Jaghori, B Kurlan, R Pauls, DL Sandor, P Barr, CL Kidd, KK AF Paschou, P Feng, Y Pakstis, AJ Speed, WC DeMille, MM Kidd, JR Jaghori, B Kurlan, R Pauls, DL Sandor, P Barr, CL Kidd, KK TI Indications of linkage and association of Gilles de la Tourette syndrome in two independent family samples: 17q25 is a putative susceptibility region SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; TYROSINE KINASE SUBSTRATE; AUTOSOMAL-DOMINANT TRANSMISSION; PROGRESSIVE-MOTOR-NEURONOPATHY; D4 RECEPTOR LOCUS; INSULIN-RECEPTOR; BIPOLAR DISORDER; SEGREGATION ANALYSIS; MISSENSE MUTATION; TIC SEVERITY AB Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS remains elusive. However, several genomic regions have been implicated. Among them, 17q25 appears to be of special interest, as suggested by various independent investigators. In the present study, we explored the possibility that 17q25 contributes to the genetic component of GTS. The initial scan of chromosome 17 performed on two large pedigrees provided a nonparametric LOD score of 2.41 near D17S928. Fine mapping with 17 additional microsatellite markers increased the peak to 2.61 (P = .002). The original families, as well as two additional pedigrees, were genotyped for 25 single-nucleotide polymorphisms (SNPs), with a focus on three genes in the indicated region that could play a role in the development of GTS, on the basis of their function and expression profile. Multiple three-marker haplotypes spanning all three genes studied provided highly significant association results (P < .001). An independent sample of 96 small families with one or two children affected with GTS was also studied. Of the 25 SNPs, 3 were associated with GTS at a statistically significant level. The transmission/disequilibrium test for a three-site haplotype moving window again provided multiple positive results. The background linkage disequilibrium (LD) of the region was studied in eight populations of European origin. A complicated pattern was revealed, with the pairwise tests producing unexpectedly high LD values at the telomeric TBCD gene. In conclusion, our findings warrant the further investigation of 17q25 as a candidate susceptibility region for GTS. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Hosp Sick Children, Dept Psychiat, Brain & Behav Programme, Toronto, ON M5G 1X8, Canada. Univ Rochester, Sch Med, Dept Neurol, Cognit & Behav Neurol Unit, Rochester, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Paschou, P (reprint author), Yale Univ, Sch Med, Dept Genet, Room I-347 Sterling Hall,333 Cedar St, New Haven, CT 06520 USA. EM peristera.paschou@yale.edu OI DeMille, Mellissa/0000-0001-7068-395X; Barr, Cathy/0000-0003-0361-0106 FU NINDS NIH HHS [R01 NS040024, R01-NS40024] NR 82 TC 39 Z9 44 U1 4 U2 8 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 OCT PY 2004 VL 75 IS 4 BP 545 EP 560 DI 10.1086/424389 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 850SZ UT WOS:000223634100002 PM 15303240 ER PT J AU Dhingra, R Pencina, MJ Benjamin, EJ Levy, D Larson, MG Meigs, JB Rifai, N D'Agostino, RB Vasan, RS AF Dhingra, R Pencina, MJ Benjamin, EJ Levy, D Larson, MG Meigs, JB Rifai, N D'Agostino, RB Vasan, RS TI Cross-sectional relations of urinary sodium excretion to cardiac structure and hypertrophy - The Framingham Heart Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE sodium; hypertrophy; left ventricle; echocardiography; epidemiology ID LEFT-VENTRICULAR MASS; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; DIETARY-SODIUM; SALT INTAKE; INVOLVEMENT; PREDICTION; DISEASE; RISK AB Background: Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP, in the community. Methods: We analyzed the cross-sectional relationships between urinary sodium excretion and LV measurements in a community-based sample of 2660 Framingham Offspring Study participants (mean age 58 years, 56% women and 44% men). Participants with known coronary artery disease, congestive heart failure, or renal failure as well as those using diuretics were excluded. Urinary sodium excretion was measured on a spot urine sample and was indexed to urinary creatinine. Results: In sex-specific, multivariable linear regression models adjusting for covariates known to influence LV measurements, log urinary sodium was not associated with LV mass, wall thickness, end-diastolic dimensions, or left atrial size in either sex. Urinary sodium was not related to LVH defined as LV mass sex-specific 80th percentile value. In analyses restricted to hypertensive individuals (n = 983, 470 women), urinary sodium was not associated with LV mass or LVH. Conclusions: In our large community-based sample, urinary sodium excretion was not related to LV mass, function, or hypertrophy. (C) 2004 American Journal of Hypertension, Ltd. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Boston Univ, Med Ctr, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288, 2K24HL04334, N01-HC-25195] NR 35 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2004 VL 17 IS 10 BP 891 EP 896 DI 10.1016/j.amjhyper.2004.06.008 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 862PA UT WOS:000224501900005 PM 15485750 ER PT J AU Hutt, E Reznickova, N Morgenstern, N Frederickson, E Kramer, AM AF Hutt, E Reznickova, N Morgenstern, N Frederickson, E Kramer, AM TI Improving care for nursing home-acquired pneumonia in a managed care environment SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CONTROLLED TRIAL; RESIDENTS; FACILITIES; GUIDELINES; IMPROVEMENT; INFLUENZA; MORTALITY; PROGRAM; VACCINATION; PREVENTION AB Objective: To characterize care of nursing home residents who became ill with nursing home-acquired pneumonia (NHAP) in a group-model, nonprofit HMO, and to pilot-test a strategy to implement evidence-based NHAP care guidelines. Study Design: Medical record review and intervention pilot test. Methods: Nursing home medical records of 78 patients who developed NHAP in 6 homes where the HMO contracts for Medicare services were reviewed for demographics, functional status, comorbidity, NHAP severity, care processes, and guideline compliance. The intervention, combining organizational change (facilitating immunization and providing appropriate emergency antibiotics) and education (quarterly in-services for nursing and aide staff), was pilot-tested for 7 months in I facility. Measures of baseline and intervention guideline adherence at that facility were compared with Fisher's exact test. Results: Among the patients with NHAP, 83% had a response from their physician in less than 8 hours, 82% were treated with an antibiotic that met spectrum recommendations, and 74% were able to swallow were treated with oral antibiotics. However, few patients had documentation of influenza and pneumococcal vaccination; less than half the direct care staff had been vaccinated; and nursing assessments were incomplete for 23%. At the pilot-test facility, improvement was seen in influenza vaccination (14% to 52%, P = .01) and use of the most appropriate antibiotics (47% to 85%; P = .03). The guideline adherence score improved from 52% to 63% (P = .04). Conclusion: Use of a multidisciplinary, multifaceted intervention resulted in improvement in quality of care for nursing home residents who become ill with pneumonia. C1 Denver VAMC, Program Improve Qual Life & Care Vet LTC, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, Denver, CO USA. Kaiser Permanente, Denver, CO USA. RP Hutt, E (reprint author), Denver VAMC, Program Improve Qual Life & Care Vet LTC, 151,1055 Clermont St, Denver, CO 80220 USA. EM evelyn.hutt@uchsc.edu NR 27 TC 9 Z9 9 U1 0 U2 4 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 OCT PY 2004 VL 10 IS 10 BP 681 EP 686 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 862QA UT WOS:000224504600006 PM 15521159 ER PT J AU Bullen, JW Ziotopoulou, M Ungsunan, L Misra, J Alevizos, I Kokkotou, E Maratos-Flier, E Stephanopoulos, G Mantzoros, CS AF Bullen, JW Ziotopoulou, M Ungsunan, L Misra, J Alevizos, I Kokkotou, E Maratos-Flier, E Stephanopoulos, G Mantzoros, CS TI Short-term resistance to diet-induced obesity in A/J mice is not associated with regulation of hypothalamic neuropeptides SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE neuropeptides; energy homeostasis; uncoupling protein-2; interleukin-1; microarray ID MELANIN-CONCENTRATING HORMONE; PROOPIOMELANOCORTIN MESSENGER-RNA; TYROSINE-PHOSPHATASE 1B; SIGNAL-TRANSDUCTION; LEPTIN RESISTANCE; BODY-WEIGHT; INSULIN SENSITIVITY; FEEDING-BEHAVIOR; C57BL/6J MICE; EXPRESSION AB To investigate the mechanisms underlying long-term resistance of the A/J mouse strain to diet-induced obesity, we studied, over a period of 4 wk, the expression of uncoupling proteins in brown adipose tissue and the expression of hypothalamic neuropeptides known to regulate energy homeostasis and then used microarray analysis to identify other potentially important hypothalamic peptides. Despite increased caloric intake after 2 days of high-fat feeding, body weights of A/J mice remained stable. On and after 1 wk of high-fat feeding, A/J mice adjusted their food intake to consume the same amount of calories as mice fed a low-fat diet; thus their body weight and insulin, corticosterone, free fatty acid, and glucose levels remained unchanged for 4 wk. We found no changes in hypothalamic expression of several orexigenic and/or anorexigenic neuropeptides known to play an important role in energy homeostasis for the duration of the study. Uncoupling protein-2 mRNA expression in brown adipose tissue, however, was significantly upregulated after 2 days of high-fat feeding and tended to remain elevated for the duration of the 4-wk study. Gene array analysis revealed that several genes are up- or downregulated in response to 2 days and 1 wk of high-fat feeding. Real-time PCR analysis confirmed that expression of the hypothalamic IL-1 pathway (IL-1beta, IL-1 type 1 and 2 receptors, and PPM1b/PP2C-beta, a molecule that has been implicated in the inhibition of transforming growth factor-beta-activated kinase-1-mediated IL-1 action) is altered after 2 days, but not 1 wk, of high-fat feeding. The role of additional molecules discovered by microarray analysis needs to be further explored in the future. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol, ST 816,330 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 49 TC 11 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2004 VL 287 IS 4 BP E662 EP E670 DI 10.1152/ajpendo.00114.2004 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 852XZ UT WOS:000223791400010 PM 15361355 ER PT J AU Vallance, BA Dijkstra, G Qiu, BS van der Waaij, LA van Goor, H Jansen, PLM Mashimo, H Collins, SM AF Vallance, BA Dijkstra, G Qiu, BS van der Waaij, LA van Goor, H Jansen, PLM Mashimo, H Collins, SM TI Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE mucus; bacteria; inflammatory bowel diseases; goblet cells ID NITRIC-OXIDE SYNTHASE; INFLAMMATORY-BOWEL-DISEASE; CHRONIC GRANULOMATOUS COLITIS; COLON EPITHELIAL-CELLS; ULCERATIVE-COLITIS; CROHNS-DISEASE; INTESTINAL INFLAMMATION; GASTROINTESTINAL-TRACT; MICE LACKING; EXPRESSION AB The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating mucosal integrity in response to noxious stimuli. To date, studies examining the roles of the NOS isoforms in experimental colitis have been conflicting, and the mechanisms by which these enzymes exert their effects remain unclear. To investigate and clarify the roles of the NOS isoforms in gut inflammation, we induced trinitrobenzenesulfonic acid colitis in eNOS, nNOS, and iNOS knockout (KO) mice, assessing the course of colitis at early and late times. Both eNOS and iNOS KO mice developed a more severe colitis compared with wild-type mice. During colitis, iNOS expression dramatically increased on epithelial and lamina propria mononuclear cells, whereas eNOS expression remained localized to endothelial cells. Electron and fluorescence microscopy identified bacteria in the ulcerated colonic mucosa of eNOS KO mice, but not in wild-type, iNOS, or nNOS KO mice. Furthermore, eNOS KO mice had fewer colonic goblet cells, impaired mucin production, and exhibited increased susceptibility to an inflammatory stimulus that was subthreshold to other mice. This susceptibility was reversible, because the NO donor isosorbide dinitrate normalized goblet cell numbers and ameliorated subsequent colitis in eNOS KO mice. These results identify a protective role for both iNOS and eNOS during colitis, with eNOS deficiency resulting in impaired intestinal defense against lumenal bacteria and increased susceptibility to colitis. C1 British Columbia Childrens Hosp, ABC, Div Gastroenterol, Vancouver, BC V6H 3V4, Canada. McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada. McMaster Univ, Intestinal Dis Res Program, Hamilton, ON L8N 3Z5, Canada. Univ Groningen Hosp, Dept Gastroenterol, Groningen, Netherlands. Univ Groningen Hosp, Dept Pathol, Groningen, Netherlands. Massachusetts Gen Hosp, Dept Vet Affairs Med Ctr, Boston, MA 02132 USA. RP Vallance, BA (reprint author), British Columbia Childrens Hosp, ABC, Div Gastroenterol, Rm K4-201,Rm K4-201,4480 Oak St, Vancouver, BC V6H 3V4, Canada. EM bvallance@cw.bc.ca RI Jansen, Peter/I-4509-2013; OI Vallance, Bruce/0000-0003-1345-6747 NR 62 TC 39 Z9 41 U1 0 U2 1 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 OCT PY 2004 VL 287 IS 4 BP G865 EP G874 DI 10.1152/ajpgi.00187.2004 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 852XY UT WOS:000223791300015 PM 15217783 ER PT J AU Nagami, GT AF Nagami, GT TI Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG II SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ammonia transport; ammoniagenesis; acid-base physiology; losartan ID CHRONIC METABOLIC-ACIDOSIS; RAT NEPHRON SEGMENTS; ANGIOTENSIN-II; PERFUSED INVITRO; EXCRETION; MICROPUNCTURE; MEMBRANE AB ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH(4)Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice. By contrast, when ANG II was present in the luminal perfusion solution, ammonia production and secretion rates were stimulated, in a losartan-inhibitable manner, to a greater extent in S3 segments from acidotic mice. Ammonia secretion rates in S3 segments were largely inhibited by perfusion with a low-sodium solution containing amiloride in the presence or absence of ANG II. These results demonstrated that isolated, perfused mouse S3 proximal tubule segments produce and secrete ammonia, that NH(4)Cl-induced acidosis does not affect the basal rates of ammonia production and secretion, and that ANG II, added to the luminal fluid, stimulates ammonia production and secretion to a greater extent in S3 segments from acidotic mice. These findings suggest that S3 segments, in the presence of ANG II, can contribute to the enhanced renal excretion that occurs with acid loading. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Nagami, GT (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 31 TC 18 Z9 18 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2004 VL 287 IS 4 BP F707 EP F712 DI 10.1152/ajprenal.00189.2003 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 851CZ UT WOS:000223664300014 PM 15345494 ER PT J AU Weitzman, ER Nelson, TF Lee, H Wechsler, H AF Weitzman, ER Nelson, TF Lee, H Wechsler, H TI Reducing drinking and related harms in college evaluation - Evaluation of the "A matter of degree" program SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RANDOMIZED COMMUNITY TRIAL; BINGE-DRINKING; ALCOHOL-USE; HARVARD-SCHOOL; PREVENTION; STUDENTS; HEALTH; INTERVENTIONS; AVAILABILITY; EPIDEMIOLOGY AB Objectives: To examine the effects of a multisite environmental prevention initiative, the "A Matter of Degree" (AMOD) program, on student heavy alcohol Consumption and resultant harms at tell colleges. Methods: A quasi-experimental longitudinal analysis of alcohol consumption and harms was employed, using repeated cross-sectional survey data from the Harvard School of Public Health College Alcohol Study (CAS). Areas examined included seven measures of alcohol consumption, thirteen measures of alcohol-related harms, and eight measures of secondhand effects of alcohol use by others. Comparisons were conducted oil self-reported behavior of students for the ten AMOD sites in aggregate and by level of program implementation, with students at 32 comparison colleges in the CAS, for each Outcome. Results: No statistically significant change was found in the overall ten-school AMOD program for outcome measures of interest from baseline (1997) to follow-up (2001). However, there was variation in the degree of environmental program development within AMOD during the intervention period. A pattern of statistically significant decreases in alcohol consumption, alcohol-related harms, and secondhand effects was observed, reflecting minor to more substantial changes across measures among students at the five program colleges that most closely implemented the AMOD model of environmental change. No similar pattern was observed for the low implementation sites or at 32 comparison colleges. Conclusions: While there was no change in the ten AMOD schools in study measures, significant although small improvements in alcohol consumption and related harms at colleges were observed among students at the five AMOD sites that most closely implemented the environmental model. Fidelity to a program model conceptualized around changing alcohol-related policies, marketing, and promotions may reduce college student alcohol consumption and related harms. Further research is needed over the full course of the AMOD program to identify, critical intervention components and elucidate pathways by which effects are realized. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Landmark Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. RP Weitzman, ER (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Landmark Ctr, 401 Pk Dr,POB 15678, Boston, MA 02215 USA. EM cweitzman@hsph.harvard.edu NR 60 TC 61 Z9 61 U1 2 U2 9 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 OCT PY 2004 VL 27 IS 3 BP 187 EP 196 DI 10.1016/j.amepre.2004.06.008 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 857IM UT WOS:000224109800001 PM 15450630 ER PT J AU Murff, HJ Byrne, D Syngal, S AF Murff, HJ Byrne, D Syngal, S TI Cancer risk assessment - Quality and impact of the family history interview SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; BREAST-CANCER; PRIMARY-CARE; PROSTATE-CANCER; OVARIAN-CANCER; ENDOMETRIAL CANCER; GENETICS SERVICES; COMPUTER SUPPORT; GPS VIEWS; WOMEN AB Background: Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. Methods: Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. Results: Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI] = 34%-44% vs 16%, 95% CI=12%-20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, -18% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. Conclusions: Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services. (C) 2004 American Journal of Preventive Medicine. C1 Vanderbilt Univ, Ctr Med, Div Gen Internal Med, Nashville, TN 37240 USA. Tennessee Valley Healthcare Syst, Dept Vet Affairs, Nashville, TN USA. Brigham & Womens Hosp, Div Populat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, 4 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org FU NCI NIH HHS [K07CA08453] NR 65 TC 51 Z9 53 U1 1 U2 4 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 OCT PY 2004 VL 27 IS 3 BP 239 EP 245 DI 10.1016/j.amepre.2004.05.003 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 857IM UT WOS:000224109800008 PM 15450637 ER PT J AU Adler, LE Olincy, A Cawthra, EM McRae, KA Harris, JG Nagamoto, HT Waldo, MC Hall, MH Bowles, A Woodward, L Randal, R Freedman, R AF Adler, LE Olincy, A Cawthra, EM McRae, KA Harris, JG Nagamoto, HT Waldo, MC Hall, MH Bowles, A Woodward, L Randal, R Freedman, R TI Varied effects of atypical neuroleptics on P50 auditory gating in schizophrenia patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROPHYSIOLOGICAL EVIDENCE; STIMULATION INTERVAL; ANTIPSYCHOTIC-DRUGS; EVOKED-RESPONSES; SUPPRESSION; CLOZAPINE; RELATIVES; DEFICITS; NORMALIZATION; HABITUATION AB Objective: Sensory gating deficits found in schizophrenia can be assessed by using a paired auditory stimulus paradigm to measure auditory evoked response, The ratio of the P50 response amplitude of the second or test stimulus to that of the first or conditioning stimulus is expressed as a percentage. Normal subjects generally suppress the second response and typically have ratios of less than 40%. Subjects with schizophrenia and half their first-degree relatives have deficits in sensory gating, with P50 ratios that are generally greater than 50%. Treatment with typical neuroleptics does not reverse this deficit. However, previous studies have shown that treatment with clozapine, an atypical neuroleptic, ameliorates this deficit in clinically responsive patients. This study sought to determine whether other atypical neuroleptics improve P50 ratios. Method: P50 evoked potential recordings were obtained from 132 patients with schizophrenia and 177 healthy comparison subjects. Eighty-eight patients were being treated with atypical neuroleptics (clozapine [N=26], olanzapine [N=31], risperidone [N=22], and quetiapine [N=9]). Thirty-four patients were taking typical neuroleptics, and 10 were unmedicated. Results: Healthy subjects exhibited P50 suppression that was significantly better than the schizophrenia patients receiving typical neuroleptics (mean=19.8% [SD= 21.0%] versus 110.1% [SD=87.9%]). Patients receiving atypical neuroleptics had a mean P50 ratio that fell between these two means (mean=70.4%, SD=53.7%). When patients treated with different atypical neuroleptics were compared, only the clozapine group had mean P50 ratios that were in the normal range. All other groups exhibited auditory P50 response inhibition that was significantly poorer than that of the healthy subjects. Conclusions: Improvement in P50 gating appears to be greatest in patients treated with clozapine. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Waldo, MC (reprint author), Univ Colorado, Hlth Sci Ctr, Box C268-26,4200 E 9th Ave, Denver, CO 80262 USA. EM merilyne.waldo@uchsc.edu RI Hall, Mei-Hua/A-3674-2008 OI Hall, Mei-Hua/0000-0002-4558-7023 FU NIMH NIH HHS [5R01-MH-50787, 5R0-MH-38321, 2K02-MH-01121] NR 46 TC 127 Z9 136 U1 3 U2 4 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 OCT PY 2004 VL 161 IS 10 BP 1822 EP 1828 DI 10.1176/appi.ajp.161.10.1822 PG 7 WC Psychiatry SC Psychiatry GA 859OY UT WOS:000224279000016 PM 15465979 ER PT J AU Rosen, J Mulsant, BH Bruce, ML Mittal, V Fox, D AF Rosen, J Mulsant, BH Bruce, ML Mittal, V Fox, D TI Actors' portrayals of depression to test interrater reliability in clinical trials SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STUDENTS AB Objective: This study determined if actors could portray depressed patients to establish the interrater reliability of raters using the Hamilton Depression Rating Scale (HDRS). Method: Actors portrayed depressed patients using scripts derived from HDRS assessments obtained at three points during treatment. Four experienced raters blindly viewed videotapes of two patients and two actors. They guessed if each interviewee was a patient or an actor and rated the certainty of their guesses. For each interview, they also rated the realism of the portrayal and completed the HDRS. Results: Experienced raters could not distinguish actors and patients better than chance and were equally certain of their right and wrong guesses. Actors and patients received high scores on the realism of their portrayals. The HDRS scores of the actor-patient pairs were correlated. Conclusions: Actors can effectively portray depressed patients. Future studies will determine if actors can accurately portray patients with anxiety and psychosis. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Katz Grad Sch Business, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. Cornell Univ, Weill Med Coll, White Plains, NY USA. Fox Learning Syst Inc, Bridgeville, PA USA. RP Mulsant, BH (reprint author), 3811 O Hara St, Pittsburgh, PA 15213 USA. EM mulsantbh@upmc.edu FU AHRQ HHS [HS-11976]; NIA NIH HHS [AG-19088]; NIMH NIH HHS [MH-01634, MH-61639, MH-01613, MH-52247] NR 9 TC 5 Z9 5 U1 0 U2 0 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 OCT PY 2004 VL 161 IS 10 BP 1909 EP 1911 DI 10.1176/appi.ajp.161.10.1909 PG 3 WC Psychiatry SC Psychiatry GA 859OY UT WOS:000224279000027 PM 15465990 ER PT J AU Hirashima, F Parow, AM Stoll, AL Demopulos, CM Damico, KE Rohan, ML Eskesen, JG Zuo, CS Cohen, BM Renshaw, PF AF Hirashima, F Parow, AM Stoll, AL Demopulos, CM Damico, KE Rohan, ML Eskesen, JG Zuo, CS Cohen, BM Renshaw, PF TI Omega-3 fatty acid treatment and T-2 whole brain relaxation times in bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MEMBRANE-FLUIDITY; METABOLISM; ACIDS AB Objective: The authors hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T-2 values. Method: Women with bipolar disorder (N=12) received omega-3 fatty acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar disorder (N=12) did not receive omega-3 fatty acids. T-2 values were acquired at baseline and after 4 weeks. Results: Bipolar subjects who received omega-3 fatty acids had significant decreases in T-2. There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts. Conclusions: Omega-3 fatty acids lowered T-2 values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T-2 values. C1 Brain Imaging Ctr, Belmont, MA USA. McLean Hosp, Psychopharmacol Res Lab, Belmont, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA USA. RP Hirashima, F (reprint author), 23A Melview Ridge, Norwich, VT 05055 USA. EM fuyuki@alum.dartmouth.org FU NIMH NIH HHS [MH-58681] NR 13 TC 67 Z9 70 U1 1 U2 4 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 OCT PY 2004 VL 161 IS 10 BP 1922 EP 1924 DI 10.1176/appi.ajp.161.10.1922 PG 3 WC Psychiatry SC Psychiatry GA 859OY UT WOS:000224279000032 PM 15465995 ER PT J AU Ware, LB Eisner, MD Thompson, BT Parsons, PE Matthay, MA AF Ware, LB Eisner, MD Thompson, BT Parsons, PE Matthay, MA CA Acute Resp Distress Syndrome Netwo TI Significance of Von Willebrand factor in septic and nonseptic patients with acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; sepsis; von Willebrand factor ID RESPIRATORY-DISTRESS-SYNDROME; THROMBOTIC THROMBOCYTOPENIC PURPURA; VONWILLEBRAND-FACTOR RELEASE; ENDOTHELIAL-CELL ACTIVATION; FACTOR PATHWAY INHIBITOR; FACTOR ANTIGEN LEVELS; TIDAL VOLUME; MICROVASCULAR PERMEABILITY; ORGAN DYSFUNCTION; SEVERE SEPSIS AB Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 +/- 265% of normal control plasma) and Day 3 (344 +/- 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 +/- 333%) versus survivors (306 +/- 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4-2.1). Higher VWF levels were also significantly associated with fewer organ failure-free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated. C1 Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, Nashville, TN 37232 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Environm & Occupat Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, ARDS Network Clin Coordinating Ctr, Boston, MA 02114 USA. Univ Vermont, Fletcher Allen Hlth Care, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. RP Ware, LB (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, T1217 MCN, Nashville, TN 37232 USA. EM lorraine.ware@vanderbilt.edu FU NHLBI NIH HHS [HL 51856, HL 70521]; PHS HHS [46055, 46054, 46056, 46057, 46058, 46059, 46060, 46061, 46062, 46063, 46064] NR 53 TC 128 Z9 143 U1 1 U2 3 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 OCT 1 PY 2004 VL 170 IS 7 BP 766 EP 772 DI 10.1164/rccm.200310-1434OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 857JF UT WOS:000224111800011 PM 15201135 ER PT J AU Tager, AM Kradin, RL LaCamera, P Bercury, SD Campanella, GSV Leary, CP Polosukhin, V Zhao, LH Sakamoto, H Blackwell, TS Luster, AD AF Tager, AM Kradin, RL LaCamera, P Bercury, SD Campanella, GSV Leary, CP Polosukhin, V Zhao, LH Sakamoto, H Blackwell, TS Luster, AD TI Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10 SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID INDUCIBLE PROTEIN-10; IFN-GAMMA; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; IP-10 CHEMOKINE; LUNG INJURY; IN-VIVO; ANGIOGENESIS; CELLS; EXPRESSION AB Pulmonary fibrosis is an enigmatic and devastating disease with few treatment options, now thought to result from abnormal wound healing in the lung in response to injury. We have previously noted a role for the chemokine interferon gamma-inducible protein of 10 kD (IP-10)/CXC chemokine ligand 10 in the regulation of cutaneous wound healing, and consequently investigated whether IP-10 regulates pulmonary fibrosis. We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin. IP-10-deficient mice exhibited increased pulmonary fibrosis after administration of bleomycin, suggesting that IP-10 limits the development of fibrosis in this model. Substantial fibroblast chemoattractant and proliferative activities were generated in the lung after bleomycin exposure. IP-10 significantly inhibited fibroblast responses to the chemotactic, but not the proliferative activity generated, suggesting that IP-10 may attenuate fibroblast accumulation in bleomycin-induced pulmonary fibrosis by limiting fibroblast migration. Consistent with this inhibitory activity of IP-10 on fibroblast migration, fibroblast accumulation in the lung after bleomycin exposure was dramatically increased in IP-10-deficient mice compared with wild-type mice. Conversely, transgenic mice overexpressing IP-10 were protected from mortality after bleomycin exposure, and demonstrated decreased fibroblast accumulation in the lung after challenge compared with wild-type mice. Our findings suggest that interruption of fibroblast recruitment may represent a novel therapeutic strategy for pulmonary fibrosis, which could have applicability to a wide range of fibrotic illnesses. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunopathol Unit, Boston, MA 02129 USA. Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Bldg 149-8301,13th St, Boston, MA 02129 USA. EM luster@helix.mgh.harvard.edu FU NCI NIH HHS [R01-CA69212]; NHLBI NIH HHS [K08-HL04087, R01-HL61419]; NIAID NIH HHS [R01-AI39054] NR 43 TC 95 Z9 100 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2004 VL 31 IS 4 BP 395 EP 404 DI 10.1165/rcmb.2004-0175OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 859VC UT WOS:000224295000003 PM 15205180 ER PT J AU Wang, EA Lee, MH Wang, MC Lee, HY AF Wang, EA Lee, MH Wang, MC Lee, HY TI Iatrogenic left iliac-caval fistula: Imaging and endovascular treatment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LUMBAR-DISK SURGERY; ARTERIOVENOUS-FISTULAS; AORTOCAVAL; ANATOMY C1 Olive View UCLA Med Ctr, Dept Radiol, Sylmar, CA 91342 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Imaging Serv, Los Angeles, CA USA. RP Lee, MH (reprint author), Olive View UCLA Med Ctr, Dept Radiol, 14445 Olive View Dr, Sylmar, CA 91342 USA. EM marglee@ucla.edu NR 8 TC 3 Z9 5 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 OCT PY 2004 VL 183 IS 4 BP 1032 EP 1034 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 858UJ UT WOS:000224217200026 PM 15385299 ER PT J AU Gervais, DA AF Gervais, DA TI Recurrent abdominal and pelvic abscesses: Incidence, results of repeated percutaneous drainage, and underlying causes in 956 drainages (Vol 182, pg 463, 2004) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Correction C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 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 OCT PY 2004 VL 183 IS 4 BP 1175 EP 1175 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 858UJ UT WOS:000224217200061 ER PT J AU Mair, SD Schlegel, TF Gill, TJ Hawkins, RJ Steadman, JR AF Mair, SD Schlegel, TF Gill, TJ Hawkins, RJ Steadman, JR TI Incidence and location of bone bruises after acute posterior cruciate ligament injury SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE posterior cruciate ligament (PCL) injury; bone bruise; collateral ligament injury; magnetic resonance imaging (MRI) ID ARTICULAR-CARTILAGE; NATURAL-HISTORY; DEFICIENT KNEE; TEARS; RUPTURE; LESIONS; CLASSIFICATION AB Background: In patients suffering from an anterior cruciate ligament injury, the incidence and location of bone bruises are well documented. This study reports data regarding bone bruises after acute posterior cruciate ligament injury. Hypothesis: Bone bruises associated with posterior cruciate ligament injury are common, and their location differs from those seen with anterior cruciate ligament injury. Study Design: Retrospective cohort study. Methods: Thirty-five consecutive patients were identified as having a grade II or III posterior cruciate ligament tear, with an intact anterior cruciate ligament, in which a magnetic resonance imaging scan had been obtained within 20 days of injury. Magnetic resonance imaging scans were reviewed to document bone bruises, associated medial or lateral ligamentous injury, and meniscal and chondral abnormalities. Results: Of the 35 patients, 29 (83%) had a bone bruise in at least one location. Bone bruises were found throughout the joint, more widely dispersed than is commonly seen with anterior cruciate ligament injury. Also, 29 patients had magnetic resonance imaging findings of associated ligamentous injury. Lateral bone bruises were associated with medial collateral ligament injury, whereas medial bone bruises correlated with posterolateral injury. Conclusions: The incidence of bone bruises associated with posterior cruciate ligament injury is similar to that seen with anterior cruciate ligament injury. Their location is more widely dispersed. The location of a bone bruise should lead to careful magnetic resonance imaging inspection and physical examination for ligamentous injury to the opposite side of the joint. Truly isolated posterior cruciate ligament injuries are rare, as most occur with osseous and some degree of associated ligamentous injury. C1 Univ Kentucky, Lexington, KY USA. Steadman Hawkins Clin & Res Fdn, Vail, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mair, SD (reprint author), Kentucky Clin, 740 S Limestone,K401, Lexington, KY 40536 USA. EM smair2@uky.edu NR 35 TC 18 Z9 21 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD OCT-NOV PY 2004 VL 32 IS 7 BP 1681 EP 1687 DI 10.1177/0363546504266481 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 863UX UT WOS:000224590000013 PM 15494333 ER PT J AU McKenney, JK Amin, MB Srigley, JR Jimenez, RE Ro, JY Grignon, DJ Young, RH AF McKenney, JK Amin, MB Srigley, JR Jimenez, RE Ro, JY Grignon, DJ Young, RH TI Basal cell proliferations of the prostate other than usual basal cell hyperplasia - A clinicopathologic study of 23 cases, including four carcinomas, with a proposed classification SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE prostate gland; adenoid cystic carcinoma; basaloid carcinoma; basal cell carcinoma; basal cell hyperplasia; adenoid basal tumor; adenoid cystic-like tumor; adenoid cystic-like hyperplasia; immunohistochemistry ID ADENOID CYSTIC CARCINOMA; SALIVARY-GLAND; TUMOR AB Basaloid proliferations of the prostate with morphologic patterns other than usual basal cell hyperplasia are rare, and the distinction between benign and malignant lesions has been difficult. We describe 23 such lesions and classify them into two groups: adenoid cystic-like hyperplasia and adenoid cystic or basaloid carcinoma. Adenoid cystic-like hyperplasia (n = 19) was characterized by an older age at presentation (mean, 71.8 years), transition zone location with background of nodular hyperplasia, multifocality, lobulation, circumscription, and small acini with occasional hyalinization. A cribriform pattern limited to small- and medium-sized glands, squamous metaplasia, and hypercellular myxoid stroma were occasionally seen. Adenoid cystic carcinoma (n = 3) was characterized by a younger age at presentation (mean, 46.0 years), peripheral zone involvement, and large acini that were often dilated and exhibited extensive interanastomoses, prominent intraglandular hyalinization, perineural invasion , and extraprostatic extension. Basaloid carcinoma (n = 1) showed infiltration between normal glands, perineural invasion, and extraprostatic extension but lacked a cribriform architecture. The degree of cytologic atypia and mitotic rate overlapped between the hyperplasia and carcinoma cases. Both hyperplastic lesions and adenoid cystic carcinomas showed a basal cell phenotype with strong immunoreactivity to cytokeratins 14 and 34betaE12, but the basaloid carcinoma was negative for these markers. In all cases, the proliferating basal cells were nonreactive for myoepithelial and prostatic secretory cell markers. The 8 patients with adenoid cystic-like hyperplasia with available follow-up information had no progression of disease (mean follow-up period, 8.6 years). One patient with adenoid cystic carcinoma died with widespread metastases, but the 3 other patients with carcinomas had no disease progression (mean follow-up period, 7.0 years). In conclusion, most florid basaloid proliferations of the prostate fall into one of two categories. In the first, there is a clear association with nodular hyperplasia (adenoid cystic-like hyperplasia) and, although cytologic atypia and mitoses may be seen, they are present within a lesion that retains an orderly, vaguely nodular (noninfiltrative) pattern. The second group of cases (adenoid cystic and basaloid carcinoma) shows a widespread, haphazard infiltrative growth pattern. This study suggests that adenoid cystic carcinomas are biologically indolent following prostatectomy but have a low risk of distant metastasis. C1 Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. McMaster Univ, Credit Valley Hosp, Dept Pathol, Mississauga, ON, Canada. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Wayne State Univ, Harper Hosp, Dept Pathol, Detroit, MI USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Amin, MB (reprint author), Emory Univ Hosp, Dept Pathol & Lab Med, Room G-167,1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM mahul_amin@emoryhealthcare.org NR 37 TC 32 Z9 39 U1 0 U2 0 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 OCT PY 2004 VL 28 IS 10 BP 1289 EP 1298 DI 10.1097/01.pas.0000138180.95581.e1 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 857IJ UT WOS:000224109400004 PM 15371944 ER PT J AU Erickson, LA Myers, JL Mihm, MC Markovic, SN Pittelkow, MR AF Erickson, LA Myers, JL Mihm, MC Markovic, SN Pittelkow, MR TI Malignant basomelanocytic tumor manifesting as metastatic melanoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE basomelanocytic; basal cell carcinoma; malignant melanoma ID SQUAMOUS-CELL CARCINOMA; BURN SCAR AB We report a case of an unusual basomelanocytic tumor from the scalp of a 56-year-old man. A 56-year-old white man presented with a scalp lesion that was biopsied and interpreted as a basal cell carcinoma. Fourteen months later, metastatic melanoma was discovered in a cervical lymph node and the liver. A subsequent biopsy from the area of the previously biopsied basal cell carcinoma of the scalp showed an invasive malignant melanoma. Immunohistochemical stains performed on the original scalp specimen showed biphasic immunohistochemical profile. A population of neoplastic cells was strongly positive for the melanocytic markers Melan-A, HMB-45, and tyrosinase and showed weak focal immunoreactivity for S-100. A second population of cells was strongly immunoreactive for keratin (wide-spectrum polyclonal antibody) and BerEp4. To our knowledge, this is the first description of a malignant basomelanocytic tumor complicated by metastatic melanoma. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Dermatol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Erickson, LA (reprint author), Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. EM erickson.lori@mayo.edu NR 15 TC 26 Z9 26 U1 0 U2 0 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 OCT PY 2004 VL 28 IS 10 BP 1393 EP 1396 DI 10.1097/01.pas.0000135526.19189.31 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 857IJ UT WOS:000224109400018 PM 15371958 ER PT J AU Khan, WA Rogers, KA Karim, MM Ahmed, S Hibberd, PL Calderwood, SB Ryan, ET Ward, HD AF Khan, WA Rogers, KA Karim, MM Ahmed, S Hibberd, PL Calderwood, SB Ryan, ET Ward, HD TI Cryptosporidiosis among Bangladeshi children with diarrhea: A prospective, matched, case-control study of clinical features, epidemiology and systemic antibody responses SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ENZYME-IMMUNOASSAY DETECTION; IMMUNOGLOBULIN-G ANTIBODIES; GUINEA-BISSAU; WEST-AFRICA; RISK-FACTORS; CHILDHOOD DIARRHEA; PERUVIAN CHILDREN; PARVUM INFECTION; BRAZIL; COMMUNITY AB We conducted a prospective case-control study to investigate the epidemiology, clinical features, and systemic antibody responses of cryptosporidiosis in Bangladeshi children. Forty-six children presenting to the International Center for Diarrheal Disease Research, Bangladesh in Dhaka, Bangladesh with diarrhea and Cryptosporidium spp. oocysts in the stool were enrolled as cases. Forty-six age-matched children with diarrhea, but without cryptosporidial infection, were enrolled as controls. Thirty cases and 23 controls returned for follow-up three weeks after discharge. Infection with Cryptosporidium spp. occurred most commonly in those less than two years of age, was accompanied by watery diarrhea and vomiting, and was more likely to be associated with persistent diarrhea. Other than duration of diarrhea, there were no significant differences in clinical or epidemiologic features between cases and controls. Cryptosporidium-specific serum IgM levels were significantly higher in cases compared with controls at presentation. In addition, there was a significant increase in serum Cryptosporidium-specific serum IgG levels over the three-week follow-up period in cases compared with controls. Within the case group, there was no difference between children with acute and persistent diarrhea in the change in IgG levels over the follow-up period. However, there was a significant difference between children with acute and persistent diarrhea in changes in both IgA and IgM levels, with persistent diarrhea being associated with a decrease in levels of both antibodies. C1 Tufts Univ, New England Med Ctr, Dept Med, Div Geog Med & Infect Dis, Boston, MA 02111 USA. Int Ctr Diarrhoeal Dis Res, Div Clin Sci, Ctr Hlth & Populat Res, Dhaka 1000, Bangladesh. Tufts Univ, New England Med Ctr, Dept Med, Div Clin Care Res, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ward, HD (reprint author), Tufts Univ, New England Med Ctr, Dept Med, Div Geog Med & Infect Dis, Box 041,750 Washington St, Boston, MA 02111 USA. EM wakhan@icddrb.org; krogers@tufts-nemc.org; asabeena@hotmail.com; mahbubul@icddrb.org; phibberd@tufts-nemc.org; scalderwood@partners.org; etryan@partners.org; hward@tufts-nemc.org FU NIAID NIH HHS [AI-58935, AI-45508, U01 AI058935]; PHS HHS [A-I07389] NR 38 TC 30 Z9 31 U1 0 U2 4 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 OCT PY 2004 VL 71 IS 4 BP 412 EP 419 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 867CY UT WOS:000224821000008 PM 15516636 ER PT J AU Weinrieb, RM O'Brien, CP AF Weinrieb, RM O'Brien, CP TI A case report of naltrexone for alcoholism in a liver transplant recipient: Side effects and safety SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEPENDENCE; NALOXONE; PAIN C1 Univ Penn, Treatment & Evaluat Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Mental Illness Res & Educ Ctr, Philadelphia, PA USA. RP Weinrieb, RM (reprint author), Univ Penn, Treatment & Evaluat Ctr, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM Weinrieb_B@mail.trc.upenn.edu NR 9 TC 5 Z9 5 U1 1 U2 1 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD OCT-DEC PY 2004 VL 13 IS 5 BP 495 EP 497 DI 10.1080/10550490490512870 PG 3 WC Substance Abuse SC Substance Abuse GA 875AW UT WOS:000225393000007 PM 15764427 ER PT J AU Maggard, MA Zingmond, D O'Connell, JB Ko, CY AF Maggard, MA Zingmond, D O'Connell, JB Ko, CY TI What proportion of patients with an ostomy (for diverticulitis) get reversed? SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 16-18, 2004 CL Santa Barbara, CA SP Amer Coll Surg, SO Calif Chapter ID QUALITY-OF-LIFE; COLOSTOMY CLOSURE; COMPLICATIONS; MORBIDITY; SURGERY; IMPACT AB A common operation for patients with complicated sigmoid diverticulitis is resection and placement of an ostomy (Hartmann procedure). This population-based study examines that proportion of ostomates who undergo reversal. In the California inpatient file, patients admitted for acute diverticulitis in 1995 were identified, including a subset that had surgical resection. Data regarding receipt of ostomy were obtained (4-year follow-up). Demographics and clinical data (procedure, ostomy reversal, time to reversal, comorbidity score, and complications) were collected. In 1995, 11,582 admissions for diverticulitis occurred in California. Of these, 24.2 per cent (n = 2808) underwent surgery at admission; 88.9 per cent were sigmoid/left colectomies; and 41.7 per cent had a Hartmann procedure. Patients with ostomies were older (P = 0.0004) and male (P = 0.03). Median comobidity score was the same for patients with or without an ostomy. Of the 1176 patients who had the Hartmann procedure, 65 per cent underwent reversal (mean 143 days). A larger proportion of men than women had their ostomies reversed (74.5% vs 55.9%, respectively, P < 0.0001). Median comorbidity scores for both groups were low, 0 for those reversed and 1 for nonreversed. Our study shows that although the majority of patients had their ostomies reversed, over 35 per cent did not at 4-year follow-up. Further studies are required to evaluate how this rate may be improved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm, Dept Gen Internal Med, Los Angeles, CA USA. RP Maggard, MA (reprint author), 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA. NR 13 TC 53 Z9 53 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2004 VL 70 IS 10 BP 928 EP 931 PG 4 WC Surgery SC Surgery GA 862CW UT WOS:000224468300023 PM 15529854 ER PT J AU Harris, BS Jay, PY Rackley, MS Izumo, S O'Brien, TX Gourdie, RG AF Harris, BS Jay, PY Rackley, MS Izumo, S O'Brien, TX Gourdie, RG TI Transcriptional regulation of cardiac conduction system development: 2004 FASEB Cardiac Conduction System Minimeeting, Washington, DC SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article; Proceedings Paper CT FASEB Experimental Biology Meeting CY APR, 2004 CL Washington, DC SP FASEB DE heart conduction system; Nkx2-5; Purkinje fibers; development; atrioventricular block ID CONGENITAL HEART-DISEASE; HOLT-ORAM-SYNDROME; PURKINJE-FIBERS; NEURAL CREST; T-GENE; MESODERM FORMATION; NKX2.5 MUTATIONS; SKELETAL-MUSCLE; EMBRYONIC HEART; BOX GENE AB The development of the complex network of specialized cells that form the atrioventricular conduction system (AVCS) during cardiac morphogenesis occurs by progressive recruitment within a multipotent cardiomyogenic lineage. Understanding the molecular control of this developmental process has been the focus of recent research. Transcription factors representative of multiple subfamilies have been identified and include members of zinc-finger subfamilies (GATA4, GATA6 HF-1b), skeletal muscle transcription factors (MyoD), T-box genes (Tbx5), and also homeodomain transcription factors (Msx2 and Nkx2.5). Mutations in some of these transcription factors cause congenital heart disease and are associated with cardiac abnormalities, including deficits within the AVCS. Mouse models that closely phenocopy known human heart disease provide powerful tools for the study of molecular effectors of AVCS development. Indeed, investigations of the Nkx2.5 haploinsufficient mouse have shown that peripheral Purkinje fibers are significantly underrepresented. This piece of data corroborates our previous work showing in chick, mouse, and humans that Nkx2.5 is elevated in the differentiating AVCS relative to adjacent working ventricular myocardial tissues. Using the chick embryo as a model, we show that this elevation of Nkx2.5 is transient in the network of conduction cells comprising the peripheral Purkinje fiber system. Functional studies using defective adenoviral constructs, which disrupt the normal variation in level of this gene, result in perturbations of Purkinje fiber phenotype. Thus, the precise spatiotemporal regulation of Nkx2.5 levels during development may be required for the progressive emergence of gene expression patterns specific to differentiated Purkinje fiber cells. Published 2004 Wiley-Liss, Inc.dagger. C1 Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Washington Univ, Sch Med, Dept Pediat, Dev Biol Unit, St Louis, MO 63110 USA. Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29425 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. RP Harris, BS (reprint author), Med Univ S Carolina, Dept Anat & Cell Biol, 171 Ashley Ave, Charleston, SC 29425 USA. EM harrisbs@musc.edu FU NHLBI NIH HHS [HL56728, HL36059]; NICHD NIH HHS [HD39946] NR 61 TC 6 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0003-276X J9 ANAT REC PART A JI Anat. Rec. Part A PD OCT PY 2004 VL 280A IS 2 BP 1036 EP 1045 DI 10.1002/ar.a.20101 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA 860JF UT WOS:000224337800014 PM 15368344 ER PT J AU Zapol, WM AF Zapol, WM TI Clifford J Woolf: Recipient of the 2004 Excellence in Research Award SO ANESTHESIOLOGY LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02115 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02115 USA. EM wzapol@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2004 VL 101 IS 4 BP 820 EP 823 DI 10.1097/00000542-200410000-00004 PG 4 WC Anesthesiology SC Anesthesiology GA 858UU UT WOS:000224218400003 PM 15461984 ER PT J AU Pontoppidan, H AF Pontoppidan, H TI From continuous positive-pressure breatbing to ventilator-induced lung injury SO ANESTHESIOLOGY LA English DT Editorial Material ID ACUTE RESPIRATORY-DISTRESS AB Continuous positive-pressure ventilation was used in eight patients with severe acute respiratory failure. Cardiac output and lung function were studied during continuous positive-pressure ventilation (mean end-expiratory pressure, 13 cm H2O) and a 30-min interval of intermittent positive-pressure ventilation. Although the mean cardiac index increased from 3.6 to 4.5 l/min per square meter of body surface area, the mean intrapulmonary shunt increased by 9% with changeover to intermittent positive-pressure ventilation. Satisfactory oxygenation was maintained in all patients during continuous positive-pressure ventilation with 50% inspired oxygen or less. With intermittent positive-pressure ventilation, arterial oxygen tension promptly fell by 161 mm of mercury, 79% occurring within 1 min. Prevention of air-space collapse during expiration and an increase in functional residual capacity probably explain improved oxygenation with continuous positive-pressure ventilation. In four patients, subcutaneous emphysema or pneumothorax developed. Weighed against the effects of prolonged hypoxemia, these complications were not severe enough to warrant cessation of continuous positive-pressure ventilation. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pontoppidan, H (reprint author), 1010 Waltham St,Apt A406, Lexington, MA 02421 USA. EM pontoppida@aol.com NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2004 VL 101 IS 4 BP 1015 EP 1017 DI 10.1097/00000542-200410000-00028 PG 3 WC Anesthesiology SC Anesthesiology GA 858UU UT WOS:000224218400027 PM 15448536 ER PT J AU Rini, C Manne, S DuHamel, KN Austin, J Ostroff, J Boulad, F Parsons, SK Martini, R Williams, SE Mee, L Sexton, S Redd, WH AF Rini, C Manne, S DuHamel, KN Austin, J Ostroff, J Boulad, F Parsons, SK Martini, R Williams, SE Mee, L Sexton, S Redd, WH TI Mothers' perceptions of benefit following pediatric stem cell transplantation: A longitudinal investigation of the roles of optimism, medical risk, and sociodemographic resources SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STRESS-RELATED GROWTH; STAGE BREAST-CANCER; QUALITY-OF-LIFE; PSYCHOSOCIAL IMPACT; COPING STRATEGIES; ADJUSTMENT; CHILDREN; PREDICTORS; PREVALENCE AB Background. This longitudinal study investigated the course and predictors of benefit finding among 144 mothers of children undergoing hematopoietic stem cell transplantation (HSCT), a severely stressful and life-threatening medical procedure. Purpose: Children's medical risk and mothers' dispositional optimism and sociodemographic resources were examined as predictors of benefit finding. The association between benefit finding and mothers' psychosocial adaptation was also investigated. Methods: Assessments occurred during hospitalization for HSCT (Time 1 [T1]) and 6 months later (Time 2 [T2]). Results: Hierarchical multiple regression analyses revealed that predictors of benefit finding differed systematically across assessments, with optimism and medical risk predicting benefit finding at both time points but sociodemographic resources predicting only T2 benefit finding. Benefit finding did not predict psychosocial adaptation until optimism was considered as a moderator of their relation: T1 benefit finding was positively associated with T2 adaptation only for mothers high in optimism. Conclusions: The need for longitudinal research on posttrauma adaptation and the utility of considering the natural history of the trauma are discussed. C1 Mt Sinai Sch Med, New York, NY 10029 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mem Sloan Kettering Canc Ctr, Bronx, NY USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Med Ctr, Evanston, IL 60208 USA. Stanford Univ, Packard Childrens Hosp, Med Ctr, Stanford, CA 94305 USA. Emory Univ, Med Ctr, Atlanta, GA 30322 USA. RP Rini, C (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM christine.rini@mssm.edu FU NIMH NIH HHS [MH57738]; PHS HHS [98-450] NR 56 TC 23 Z9 23 U1 2 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2004 VL 28 IS 2 BP 132 EP 141 DI 10.1207/s15324796abm2802_9 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 858TT UT WOS:000224215500009 PM 15454361 ER PT J AU Bos, KJ Hunter, GC Camargo, CA AF Bos, KJ Hunter, GC Camargo, CA TI Multicenter study of health education in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 81 BP S25 EP S26 DI 10.1016/j.annemergmed.2004.07.086 PG 2 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300083 ER PT J AU Kabrhel, C Camargo, CA Goldharber, SZ AF Kabrhel, C Camargo, CA Goldharber, SZ TI Clinical gestalt and the diagnosis of pulmonary embolism: Does experience matter? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 118 BP S37 EP S38 DI 10.1016/j.annemergmed.2004.07.123 PG 2 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300119 ER PT J AU Kline, JA Novobilski, AJ Kabrhel, C Courtney, DM AF Kline, JA Novobilski, AJ Kabrhel, C Courtney, DM TI Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Tennessee, Chattanooga, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 3 BP S2 EP S2 DI 10.1016/j.annemergmed.2004.07.008 PG 1 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300004 ER PT J AU Nelson, BP Senecal, EL Ptak, T Thomas, SH AF Nelson, BP Senecal, EL Ptak, T Thomas, SH TI Opioid analgesia for acute abdominal pain in the elderly: Is the diagnosis of gallbladder pathology hindered? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 288 BP S89 EP S89 DI 10.1016/j.annemergmed.2004.07.290 PG 1 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300291 ER PT J AU Patel, PA Camargo, CA McLaughlin, T Leibman, C AF Patel, PA Camargo, CA McLaughlin, T Leibman, C TI The risk of recurrent emergency department visits or hospitalization in asthmatic children given different asthma medications SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 AstraZeneca LP, Wilmington, DE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NDC Hlth, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 121 BP S38 EP S38 DI 10.1016/j.annemergmed.2004.07.126 PG 1 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300122 ER PT J AU Sun, BC Emond, J Camargo, CA AF Sun, BC Emond, J Camargo, CA TI Characteristics and admission patterns of patients presenting with syncope to US emergency departments, 1992-2000 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2004 VL 44 IS 4 SU S MA 11 BP S4 EP S4 DI 10.1016/j.annemergmed.2004.07.016 PG 1 WC Emergency Medicine SC Emergency Medicine GA 859WZ UT WOS:000224300300012 ER PT J AU Treon, SP Branagan, AR Hunter, Z Santos, D Tournhilac, O Anderson, KC AF Treon, SP Branagan, AR Hunter, Z Santos, D Tournhilac, O Anderson, KC TI Paradoxical increases in serum IgM and viscosity levels following rituximab in Waldenstrom's macroglobulinemia SO ANNALS OF ONCOLOGY LA English DT Article DE hyperviscosity; rituximab; serum IgM; Waldenstrom's macroglobulinemia ID CONSENSUS PANEL RECOMMENDATIONS; ANTIBODY-MEDIATED IMMUNOTHERAPY; 2ND INTERNATIONAL WORKSHOP; COMBINATION; THERAPY AB Background: The anti-CD20 monoclonal antibody rituximab is an important therapeutic in Waldenstrom's macroglobulinemia (WM), producing response rates of 50-70%. Responses, which are based on serum IgM levels, have typically been evaluated at 12 weeks. Paradoxically, we have observed that serum I-M levels can abruptly rise following rituximab therapy in patients with WM, and can often lead to morbidity on the basis of hyperviscosity. Patients and methods: Eleven WM patients with CD20+ tumor cells who received rituximab at our Institution and had serum IgM levels measured within a 12-week period following start of therapy were evaluated. Therapy consisted of four weekly infusions of rituximab at 375 mg/m(2). Pre- and post-therapy serum IgM levels were determined by nephelometry and corresponding serum viscosity levels were determined by viscometry. Results: Ten of the 11 patients demonstrated an abrupt rise in serum IgM levels, with a >25% increase occurring in eight (73%) patients. Mean serum IgM levels for all 10 spiking patients rose from 4370 (range, 655-7940) to a peak of 5865 (range, 872-11 800) mg/dl (P=0.004), which occurred at a mean of 4 (range, 1-8) weeks following initiation of therapy. Mean serum viscosity levels also increased from 3.5 to 5.6 centipoise (CP) (P=0.09) in eight patients for whom pre- and post-therapy studies were obtained. A subdural hemorrhage occurred in one patient when serum IgM levels rose from 7530 to 11 800 mg/dl, and serum viscosity increased from 3.9 to 10.1 CP. Two other spiking patients with pre-therapy IgM levels of >5000 mg/dl experienced worsening headaches and/or epistaxis attributed to increasing serum viscosity. Conclusions: Abrupt increases in serum IgM levels commonly occur following rituximab therapy in WM. Careful clinical and laboratory monitoring is warranted, particularly if patients have pretherapy serum IgM levels of >5000 mg/dl. The mechanism of this effect is under active investigation. and may be related to CD20 signaling triggered by rituximab. C1 Dana Farber Canc Inst, Waldenstrom Macroglobulinemia Program, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA 02116 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, LG102,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [K23 CA087977-03] NR 14 TC 68 Z9 68 U1 0 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 OCT PY 2004 VL 15 IS 10 BP 1481 EP 1483 DI 10.1093/annonc/mdh403 PG 3 WC Oncology SC Oncology GA 861GX UT WOS:000224405200007 PM 15367407 ER PT J AU Bertagnolli, M Miedema, B Redston, M Dowell, J Niedzwiecki, D Fleshman, J Bem, J Mayer, R Zinner, M Compton, C AF Bertagnolli, M Miedema, B Redston, M Dowell, J Niedzwiecki, D Fleshman, J Bem, J Mayer, R Zinner, M Compton, C TI Sentinel node staging of resectable colon cancer - Results of a multicenter study SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Surgical-Association CY APR 15-17, 2004 CL San Francisco, CA SP Amer Surg Assoc ID COLORECTAL-CANCER; LYMPH-NODES; VALIDATION; TRIAL; LYMPHADENECTOMY; MICROMETASTASES; SURVIVAL AB Objective and Summary Background Data: Sentinel lymph node (LN) sampling, a technique widely used to manage breast cancer and melanoma, seeks to select LNs that accurately predict regional node status and can be extensively examined to identify nodal metastatic disease not detected by standard histopathological staging. For patients with resectable colon cancer, improved identification of LN disease would significantly advance patient care by identifying patients likely to benefit from adjuvant therapy. This study, conducted by 25 surgeons at 13 institutions, examined whether sentinel node (SN) sampling accurately predicted LN status for patients with resectable colon cancer. Methods: SN sampling involved peritumor injection of 1% isosulfan blue, followed by identification of all LN visualized within 10 minutes. SN sampling was performed on 79 of 91 patients enrolled, followed by multilevel sectioning (MLS) of the nodes and examination by a single study pathologist. Results: By standard histopathology, 7 patients had primary disease that was either benign or not colon cancer and were therefore excluded from further studies. Of 72 colon cancer cases studied, 48 (66%) were node-negative and 24 (33%) contained nodal metastases. SNs were successfully located in 66 cases (92%), with an average of 2.1 nodes per patient. SNs were negative in 14 of 24 node-positive cases (58%). MLS revealed tumor in a SN in I of these cases, bringing the false-negative rate of SN examination to 54%. Conclusion: This multi-institutional study found that for patients with node-positive colon cancer, SN examination with MLS failed to predict nodal status in 54% of cases. We conclude that SN sampling with MLS, used alone, is unlikely to improve risk stratification for resectable colon cancer. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Duke Univ, CALGB Stat Ctr, Durham, NC USA. Washington Univ, Med Ctr, St Louis, MO USA. SUNY Upstate Med Univ, Syracuse, NY USA. Vet Adm Med Ctr, Syracuse, NY 13210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Bertagnolli, M (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org FU NCI NIH HHS [U10 CA045418, CA04326, CA12046, CA21060, CA31946, CA32291, CA33601, CA37135, CA45418, CA47642, CA59594, CA77298, CA77406, CA77440, CA77658, U10 CA032291, U10 CA033601, U10 CA047642, U10 CA077440, U10 CA077658] NR 21 TC 100 Z9 103 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 2004 VL 240 IS 4 BP 624 EP 628 DI 10.1097/01.sla.000140753.41357.20 PG 5 WC Surgery SC Surgery GA 857GT UT WOS:000224105100013 PM 15383790 ER PT J AU Ommeh, S Nduati, E Mberu, E Kokwaro, G Marsh, K Rosowsky, A Nzila, A AF Ommeh, S Nduati, E Mberu, E Kokwaro, G Marsh, K Rosowsky, A Nzila, A TI In vitro activities of 2,4-diaminoquinazoline and 2,4-diaminopteridine derivatives against Plasmodium falciparum SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PYRIMETHAMINE-SULFADOXINE RESISTANCE; DIHYDROFOLATE-REDUCTASE; CHLORPROGUANIL-DAPSONE; ANTIMALARIAL ACTIVITY; MALARIA; AMODIAQUINE; COMBINATION; INHIBITORS; EFFICACY; INVITRO AB The activities of 28 6-substituted 2,4-diaminoquinazolines, 2,4-diamino-5,6,7,8-tetrahydroquinazolines, and 2,4-diaminopteridines against Plasmodium falciparum were tested. The 50% inhibitory concentrations (IC(50)s) of six compounds were <50 nM, and the most potent compound was 2,4-diamino-5-chloro-6-[N-(2,5-dimethoxybenzyl)amino]quinazoline (compound 1), with an IC50 of 9 nM. The activity of compound I was potentiated by the dihydropteroate synthase inhibitor dapsone, an indication that these compounds are inhibitors of dihydrofolate reductase. Further studies are warranted to assess the therapeutic potential of this combination in vivo. C1 KEMRI, Wellcome Trust Collaborat Res Program, Wellcome Trust Res Labs, Nairobi 00100, Kenya. Kenya Govt Med Res Ctr, Ctr Geog Med Res, Wellcome Trust Collaborat Res Program, Kilifi, Kenya. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nzila, A (reprint author), KEMRI, Wellcome Trust Collaborat Res Program, Wellcome Trust Res Labs, POB 43640 GPO, Nairobi 00100, Kenya. EM anzila@wtnairobi.mimcom.net FU FIC NIH HHS [TW 01186, R03 TW001186] NR 16 TC 16 Z9 18 U1 1 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 OCT PY 2004 VL 48 IS 10 BP 3711 EP 3714 DI 10.1128/ACC.48.10.3711-3714.2004 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 858UH UT WOS:000224217000010 PM 15388424 ER PT J AU Shelburne, SA Musher, DM Hulten, K Ceasar, H Lu, MY Bhaila, I Hamill, RJ AF Shelburne, SA Musher, DM Hulten, K Ceasar, H Lu, MY Bhaila, I Hamill, RJ TI In vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VANCOMYCIN PLUS RIFAMPIN; PROSPECTIVE MULTICENTER; BACTERICIDAL ACTIVITY; ENDOCARDITIS; INFECTIONS; THERAPY; GENTAMICIN; SUSCEPTIBILITY; EPIDEMIOLOGY; MANAGEMENT AB This study employs time-kill techniques to examine the most common drug combinations used in the therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin plus either gentamicin or rifampin. Community-associated MRSA were more likely to be synergistically inhibited by combinations of vancomycin and gentamicin versus vancomycin alone compared to inhibition associated with hospital-acquired strains. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Pediat, Houston, TX 77030 USA. RP Hamill, RJ (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM richard.hamill@med.va.gov OI Hulten, Kristina/0000-0001-7446-157X NR 32 TC 46 Z9 46 U1 0 U2 0 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 OCT PY 2004 VL 48 IS 10 BP 4016 EP 4019 DI 10.1128/AAC.48.10.4016-4019.2004 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 858UH UT WOS:000224217000055 PM 15388469 ER PT J AU Lambert, EM Strasswimmer, J Lazova, R Antaya, RJ AF Lambert, EM Strasswimmer, J Lazova, R Antaya, RJ TI Cytomegalovirus ulcer - Successful treatment with valganciclovir SO ARCHIVES OF DERMATOLOGY LA English DT Article ID VIRUS INFECTION; TRANSPLANT RECIPIENT; SKIN; DIAGNOSIS; PATIENT; HOSTS C1 Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Antaya, RJ (reprint author), Yale Univ, Sch Med, Dept Dermatol, POB 208059,333 cedar St,LCI 501, New Haven, CT 06520 USA. EM richard.antaya@yale.edu OI strasswimmer, john/0000-0002-5790-2633 NR 20 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 2004 VL 140 IS 10 BP 1199 EP 1201 DI 10.1001/archderm.140.10.1199 PG 3 WC Dermatology SC Dermatology GA 861MJ UT WOS:000224420500002 PM 15492181 ER PT J AU Vartanian, JG Carvalho, AL Yueh, B Priante, AVM de Melo, RL Correia, LM Kohler, HF Toyota, J Kowalski, ISG Kowalski, LP AF Vartanian, JG Carvalho, AL Yueh, B Priante, AVM de Melo, RL Correia, LM Kohler, HF Toyota, J Kowalski, ISG Kowalski, LP TI Long-term quality-of-life evaluation after head and neck cancer treatment in a developing country SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID EUROPEAN ORGANIZATION; VALIDATION; OUTCOMES AB Objective: To evaluate the long-term quality of life of patients treated for head and neck cancer at a single institution in a developing country. Design: Cross-sectional analysis of a consecutive series of patients. Setting: Tertiary cancer center hospital in Brazil. Patients: Eligible subjects included patients treated between 1974 and 1999 for head and neck carcinoma who had a minimum disease-free survival of 2 years and who completed a Portuguese version of the University of Washington Quality of Life (UW-QOL) questionnaire. Main Outcome Measures: Descriptive analyses of the results and comparisons of the scores for each UW-QOL domain, stratified by tumor site, were performed using nonparametric tests. Results: Findings from 344 patients were analyzed. Of the study population, 140 (41%) had survived 2 to 5 years, 125 (36%) had survived 5 to 10 years, and 79 (23%) had survived more than 10 years since treatment. Primary tumor sites were in the oral cavity in 43.3% of cases, the oropharynx in 20.9%, the larynx in 32.0%, and the hypopharynx in 3.8%. In terms of treatment, 33.1% underwent surgery alone; 16.9%, radiotherapy alone; and 50% underwent combined treatment. Overall, 78.5% of the patients classified their own health as good or excellent. Stratified analysis showed that impairment in chewing and swallowing was more common in patients with oral and oropharyngeal tumors than in those with larynx and hypopharynx tumors, and speech impairment was more frequently related to patients with larynx and hypopharynx tumors than to those with oral and oropharynx tumors. In all tumor sites, the composite scores were significantly worse in advanced tumors than early stage tumors, but the use of combined treatment had the greatest negative impact on quality-of-life scores, after we adjusted for T and N stage with multivariable analyses (P<.001). Conclusions: The Portuguese version of the UW-QOL questionnaire was an effective tool to evaluate quality of life in a Brazilian population. Although many patients reported some limitations, most reported a good to excellent long-term quality of life. C1 Hosp Canc AC Camargo, Dept Otolaryngol Head & Neck Surg, BR-01509900 Sao Paulo, Brazil. Univ Washington, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Kowalski, LP (reprint author), Hosp Canc AC Camargo, Dept Otolaryngol Head & Neck Surg, Rua Professor Antonio Prudente 211, BR-01509900 Sao Paulo, Brazil. EM lp_kowalski@uol.com.br RI Francisco, Suely/D-9065-2014; Kowalski, Luiz/D-1701-2012; Carvalho, Andre/C-1185-2011; Vartanian, Jose/B-4470-2015; Carvalho, Andre/S-7053-2016; Kowalski, Ivonete/E-3040-2017; OI Kowalski, Luiz/0000-0001-5865-9308; Carvalho, Andre/0000-0001-7214-6402; Carvalho, Andre/0000-0001-7214-6402; Kowalski, Ivonete/0000-0001-6043-0924; Yueh, Bevan/0000-0003-1380-1053; Kowalski, Luiz Paulo/0000-0002-0481-156X NR 13 TC 51 Z9 55 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2004 VL 130 IS 10 BP 1209 EP 1213 DI 10.1001/archotol.130.10.1209 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 860OT UT WOS:000224353600014 PM 15492171 ER PT J AU Hayes, SM Ryan, L Schnyer, DM Nadel, L AF Hayes, SM Ryan, L Schnyer, DM Nadel, L TI An fMRI study of episodic memory: Retrieval of object, spatial, and temporal information SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID FRONTAL-LOBE LESIONS; EVENT-RELATED FMRI; HIPPOCAMPAL-FORMATION; DECLARATIVE MEMORY; PREFRONTAL CORTEX; LOCATION; ITEM; PET; CONSOLIDATION; ACTIVATIONS AB Sixteen participants viewed a videotaped tour of 4 houses that highlighted a series of objects and their spatial locations. Participants were tested for memory of object, spatial, and temporal-order information while undergoing functional magnetic resonance imaging. Preferential activation was observed in the right parahippocampal gyrus during the retrieval of spatial-location information. Retrieval of contextual information (spatial location and temporal order) was associated with activation in the right dorsolateral prefrontal cortex. In bilateral posterior parietal regions, greater activation was associated with processing of visual scenes regardless of the memory judgment. These findings support current theories positing roles for frontal and medial temporal regions during-episodic retrieval and suggest a specific role for the hippocanipal complex in the retrieval of spatial-location information. C1 Univ Arizona, Dept Psychol, Cognit & Neuroimag Labs, Tucson, AZ 85721 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston Vet Adm Healthcare Syst, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Ryan, L (reprint author), Univ Arizona, Dept Psychol, Cognit & Neuroimag Labs, Tucson, AZ 85721 USA. EM ryant@u.arizona.edu OI Schnyer, David/0000-0002-7472-2853 FU NINDS NIH HHS [R01 NS044107-01A1, R01 NS044107, R01 NS044107-01] NR 61 TC 75 Z9 78 U1 1 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2004 VL 118 IS 5 BP 885 EP 896 DI 10.1037/0735-7044.118.5.885 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 860VN UT WOS:000224371900001 PM 15506871 ER PT J AU LaPlante, JM Ye, CP Quinn, SJ Goldin, E Brown, EM Slaugenhaupt, SA Vassilev, PM AF LaPlante, JM Ye, CP Quinn, SJ Goldin, E Brown, EM Slaugenhaupt, SA Vassilev, PM TI Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mucolipin-1; mucolipidosis; Ca2+ signaling; membrane trafficking; lysosome; channel; late endosome ID ABNORMAL TRANSPORT; LYSOSOMES; FUSION; CHANNELS; RECEPTOR; GENE; CA2+; IDENTIFICATION; EXOCYTOSIS; MUTATIONS AB Most of the membrane trafficking phenomena including those involving the interactions between endosomes and lysosomes are regulated by changes in intracellular Ca2+ (Ca-i). These processes are disturbed in some types of mucolipidoses and other lysosomal storage disorders, such as mucolipidosis IV (MLIV), a neurological disorder that usually presents during the first year of life with blindness, cognitive impairment, and psychomotor delays. It is caused by mutations in MCOLN1, the gene encoding mucolipin-1 (MLNI), which we have recently established to represent a Ca2+ -permeable cation channel that is transiently modulated by changes in Ca-i. The cells of MLIV patients contain enlarged lysosomes that are likely associated with abnormal sorting and trafficking of these and related organelles. We studied fibroblasts from MLIV patients and found disturbed Ca2+ signaling and large acidic organelles such as late endosomes and lysosomes (LEL) with altered cellular localization in these cells. The fusion between LEL vesicles in these cells was defective. This is a Ca2+-dependent process related to signaling pathways involved in regulation of Ca2+ homeostasis and trafficking. The MLN1 channels could play a key role in Ca2+ release from LEL vesicles, which triggers the fusion and trafficking of these organelles. The characterization of this MLN1-mediated Ca2+-dependent process should provide new insights into the pathophysiological mechanisms that lead to the development of MLIV and other mucolipidoses associated with similar disturbances in membrane trafficking. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Membrane Biol Program,Dept Med, Boston, MA 02115 USA. NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. RP Vassilev, PM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. EM pvassilev@rics.bwh.harvard.edu FU NINDS NIH HHS [NS39995] NR 40 TC 61 Z9 62 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 1 PY 2004 VL 322 IS 4 BP 1384 EP 1391 DI 10.1016/j.bbrc.2004.08.045 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 854ZG UT WOS:000223941900033 PM 15336987 ER PT J AU Sassi, RB Brambilla, P Hatch, JP Nicoletti, MA Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Sassi, RB Brambilla, P Hatch, JP Nicoletti, MA Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Reduced left anterior cingulate volumes in untreated bipolar patients SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2002 CL PHILADELPHIA, PA SP Soc Biol Psychiat DE affective disorders; bipolar disorder; cingulate; mood disorders; MRI; neuroimaging ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SUBGENUAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; SEASONAL AFFECTIVE-DISORDER; BRAIN GLUCOSE-METABOLISM; IN-VIVO; MOOD DISORDERS; FUNCTIONAL NEUROANATOMY; COGNITIVE IMPAIRMENT AB Background: Functional and morphologic abnormalities of the cingulate cortex have been reported in mood disorder patients. To examine the involvement of anatomic abnormalities of the cingulate in bipolar disorder, we measured the volumes of this structure in untreated and lithium-treated bipolar patients and healthy contrl subjects, using magnetic resonance imaging. Methods: the volume of gray matter at the right and left anterior and posteriorcingulate cortices were measured in 11 bipolar patientsnot taking any psychotropic medications (aged 38 +/-11 years, 5 women), 16 bipolar patients treated with lithium monotherapy (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10 years, 14 women). Volumetric measurements were made with T1-weighted control MRI images, with 1.5 mm-thick slices. at 1.5T, and were done blindly. Results: Using analysis of covariance with age and intracranial volume as covariates, we found that untreated bipolar patients had decreased left anterior cingulate with age and intracranial volume compared with healthy control subjects [2.4 +/- .3cm(3) and 2.9 +/- .6cm(3), respectively, F(1.58) = 6.4, p = 0.42] and compared with the lithium-treated patients [3.3 +/- .5cm(3) : F(1.58) = 11.7, p = .003]. The cingulate volumes in lithium-treated patients were not significantly different from those of healthy control subjects. Conclusion: Our findings indicate that anatomic abnormalities in left anterior cingulate are present in bipolar patients. Furthermore our results suggest that lithium treatment might influence cingulate volumes in bipolar patients, which could possibly reflect postulated neuroprotective effects of lithium. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. Univ Sao Paulo, Inst Psychiat, Dept Psychiat, Sch Med, Sao Paulo, Brazil. Univ Pavia, Sch Med, IRCCS, Dept Psychiat, I-27100 Pavia, Italy. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 30915, MH 01736, MH 29618] NR 88 TC 128 Z9 130 U1 5 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2004 VL 56 IS 7 BP 467 EP 475 DI 10.1016/j.biopsych.2004.07.005 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 857JV UT WOS:000224113400001 PM 15450781 ER PT J AU Antin, JH Chen, AR Couriel, DR Ho, VT Nash, RA Weisdorf, D AF Antin, JH Chen, AR Couriel, DR Ho, VT Nash, RA Weisdorf, D TI Novel approaches to the therapy of steroid-resistant acute graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review ID BONE-MARROW-TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; STEM-CELL TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; HUMAN INTERLEUKIN-1 RECEPTOR; PHASE-I TRIAL; MYCOPHENOLATE-MOFETIL; MONOCLONAL-ANTIBODY; REFRACTORY ACUTE; ADENOSINE-DEAMINASE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jantin@partners.org FU NCI NIH HHS [CA18029]; NHLBI NIH HHS [HL070149, HL36444] NR 112 TC 52 Z9 53 U1 0 U2 0 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 OCT PY 2004 VL 10 IS 10 BP 655 EP 668 DI 10.1016/j.bbmt.2004.07.007 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 860XS UT WOS:000224378100001 PM 15389432 ER PT J AU Noordin, S Shortkroff, S Sledge, CB Spector, M AF Noordin, S Shortkroff, S Sledge, CB Spector, M TI Investigation of the activation of a human serum complement protein, C3, by orthopedic prosthetic particulates SO BIOMATERIALS LA English DT Article DE complement system; biomaterials; particles; orthopaedics; prostheses; osteolysis ID POLYETHYLENE WEAR DEBRIS; TOTAL HIP-ARTHROPLASTY; BONE-RESORPTION; AIR NUCLEI; SURFACES; COMPONENTS; MEMBRANE; REMOVAL AB Myriad molecular, cellular, and physiological processes underlie the inflammatory and osteolytic processes induced by particles of biomaterials resulting from the wear of implants such as total joint replacement prostheses. The objective this study was to investigate the role that the complement system may be playing in these phenomena. The aim was to evaluate the degree to which particles of selected orthopaedic materials-high density and ultrahigh molecular weight polyethylene, polymethylmethacrylate, and commercially pure titanium-cause the elevation of a key complement molecule, On, in an in vitro assay that directly measured the concentration of On. The results demonstrated that HDPE particles, at high concentration, are capable of causing the elevation of C3a in the in vitro assay. This finding is discussed in the context of other work and the mechanics of the complement system as it may affect the osteolytic process. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, MRB 106,75 Francis St, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu NR 23 TC 7 Z9 7 U1 0 U2 2 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 OCT PY 2004 VL 25 IS 23 BP 5347 EP 5352 DI 10.1016/j.biomaterials.2003.11.057 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 822DV UT WOS:000221516900002 PM 15130719 ER PT J AU Davidov, O Zelen, M AF Davidov, O Zelen, M TI Overdiagnosis in early detection programs SO BIOSTATISTICS LA English DT Article DE early detection programs; overdiagnosis; screening ID PROSTATE-SPECIFIC ANTIGEN; CANCER INCIDENCE; BREAST-CANCER; DISEASE; LESSONS AB Overdiagnosis refers to the situation where a screening exam detects a disease that would have otherwise been undetected in a person's lifetime. The disease would have not have been diagnosed because the individual would have died of other causes prior to its clinical onset. Although the probability of overdiagnosis is an important quantity for understanding early detection programs it has not been rigorously studied. We analyze an idealized early detection program and derive the mathematical expression for the probability of overdiagnosis. The results are studied numerically for prostate cancer and applied to a variety of screening schedules. Our investigation indicates that the probability of overdiagnosis is remarkably high. C1 Univ Haifa, Dept Stat, IL-31905 Haifa, Israel. Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Davidov, O (reprint author), Univ Haifa, Dept Stat, Mt Carmel, IL-31905 Haifa, Israel. EM davidov@stat.haifa.ac.il; zelen@hsph.harvard.edu NR 24 TC 20 Z9 20 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD OCT PY 2004 VL 5 IS 4 BP 603 EP 613 DI 10.1093/biostatistics/kxh012 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 865GD UT WOS:000224689700008 PM 15475422 ER PT J AU Kilbourne, AM Cornelius, JR Han, XY Pincus, HA Shad, M Salloum, I Conigliaro, J Haas, GL AF Kilbourne, AM Cornelius, JR Han, XY Pincus, HA Shad, M Salloum, I Conigliaro, J Haas, GL TI Burden of general medical conditions among individuals with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE aging; bipolar disorder; comorbidity; diabetes mellitus; metabolic syndrome; substance-related disorders ID CARE; PREVALENCE; SUBSTANCE; LITHIUM; IMPACT; COSTS; ABUSE AB Objective: Treatment of coexisting medical comorbidities may reduce the risk of adverse outcomes among patients with bipolar disorder. We determined the prevalence of general medical conditions in a population-based sample of patients diagnosed with bipolar disorder in the Veterans Administration (VA). Methods: We conducted a cross-sectional study of patients (n = 4310) diagnosed with bipolar disorder in fiscal year 2001 receiving care at VA facilities located within the mid-Atlantic region. General medical conditions were assessed using ICD-9 codes, and we compared the prevalence of each condition in our bipolar sample with national data on the VA patient population. Results: The mean age was 53 (SD = 13), 10% were women, and 12% African-American. The mean age of the VA national patient population was higher (58 years). The most prevalent conditions among patients with bipolar disorder included cardiovascular (e.g. hypertension, 35%), endocrine (e.g. hyperlipidemia, 23%; diabetes, 17%), and alcohol use disorder (25%). When compared with national data, the prevalence of diabetes was higher in the bipolar cohort than in the national cohort (17.2% versus 15.6%; p = 0.0035). Hepatitis C was more common in the bipolar group than the national cohort (5.9% versus 1.1%; p < 0.001). Lower back pain (15.4% versus 10.6%; p < 0.0001) and pulmonary conditions (e.g. COPD: 10.6% versus 9.4%; p = 0.005) were also more prevalent among the bipolar cohort than the VA national cohort. Conclusions: Individuals with bipolar disorder possess a substantial burden of general medical comorbidity, and are occurring at an earlier age than in the general VA patient population, suggesting the need for earlier detection and treatment for patients with bipolar disorder. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C, Pittsburgh, PA 15240 USA. EM amy.kilbourne@med.va.gov FU NIMH NIH HHS [MH30915] NR 21 TC 185 Z9 191 U1 2 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2004 VL 6 IS 5 BP 368 EP 373 DI 10.1111/j.1399-5618.2004.00138.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 855TD UT WOS:000223996200003 PM 15383128 ER PT J AU Flomenberg, N Baxter-Lowe, LA Confer, D Fernandez-Vina, M Filipovich, A Horowitz, M Hurley, C Kollman, C Anasetti, C Noreen, H Begovich, A Hildebrand, W Petersdorf, E Schmeckpeper, B Setterholm, M Trachtenberg, E Williams, T Yunis, E Weisdorf, D AF Flomenberg, N Baxter-Lowe, LA Confer, D Fernandez-Vina, M Filipovich, A Horowitz, M Hurley, C Kollman, C Anasetti, C Noreen, H Begovich, A Hildebrand, W Petersdorf, E Schmeckpeper, B Setterholm, M Trachtenberg, E Williams, T Yunis, E Weisdorf, D TI Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome SO BLOOD LA English DT Article; Proceedings Paper CT 50th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY APR 28-MAY 02, 2001 CL CHICAGO, IL SP Amer Coll Obstet & Gynecol ID UMBILICAL-CORD BLOOD; HEMATOPOIETIC-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; HOST DISEASE; STEM-CELLS; FAILURE PROBABILITIES; IDENTICAL SIBLINGS; PLACENTAL-BLOOD; ALLELES; GRAFT AB Outcome of unrelated donor marrow transplantation is influenced by donor-recipient matching for HLA. Prior studies assessing the effects of mismatches at specific HLA loci have yielded conflicting results. The importance of high-resolution matching for all HLA loci has also not been established. We therefore examined the effects of HLA matching (low or high resolution or both) on engraftment, graft-versus-host disease (GVHD), and mortality in 1874 donor-recipient pairs retrospectively typed at high resolution for HLA-A, -B, -C, -DRB-1, -DQ, and -DP. Mismatches at HLA-A, -B, -C, and -DRB1 each had similar adverse effects on mortality. Only HLA-A mismatches demonstrated significant adverse effects on GVHD. These adverse effects on outcome were more evident in transplants with low-resolution versus only high-resolution mismatches. Mismatches for HLA-DQ or -DP did not significantly affect outcome. When high-resolution mismatches at HLA-A, -B, -C, and -DRB1 were considered together, adverse effects on survival and GVHD were observed. We therefore conclude that matching for HLA-C should be incorporated into algorithms for unrelated donor selection. High-resolution mismatches at HLA-A, -B, -C, and -DRB1 adversely affect outcome, but less so than low-resolution mismatches. When clinical circumstances allow, high-resolution class I typing may help optimize donor selection and improve outcome. (C) 2004 by The American Society of Hematology. C1 Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Georgetown Univ, Dept Oncol, Washington, DC USA. Childrens Hosp, Ctr Med, Cincinnati, OH USA. Int Bone Marrow Transplant Registry, Milwaukee, WI USA. Georgetown Univ, Ctr Med, Washington, DC USA. Jaeb Ctr Hlth Res, Tampa, FL USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Res Inst, Tampa, FL USA. Fairview Univ, Ctr Med, Immunol Histocompatibil Lab, Minneapolis, MN USA. Celera Diagnost, Alameda, CA USA. Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Summercrest Consulting, Columbia, MD USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. RP Flomenberg, N (reprint author), Thomas Jefferson Univ, Dept Med, 125 S 9th St Suite 801 Sheridan, Philadelphia, PA 19107 USA. EM neal.flomenberg@mail.tju.edu NR 56 TC 409 Z9 446 U1 4 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2004 VL 104 IS 7 BP 1923 EP 1930 DI 10.1182/blood-2004-03-0803 PG 8 WC Hematology SC Hematology GA 857JP UT WOS:000224112800012 PM 15191952 ER PT J AU Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Belch, AR Pilarski, LM AF Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Belch, AR Pilarski, LM TI Clonotypic IgM V/D/J sequence analysis in Waldenstrom macroglobulinemia suggests an unusual B-cell origin and an expansion of polyclonal B cells in peripheral blood SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COMPLEMENTARITY-DETERMINING REGIONS; INDUCED CYTIDINE DEAMINASE; AUTOSOMAL RECESSIVE FORM; ISOTYPE SWITCH EVENTS; HYPER-IGM; MULTIPLE-MYELOMA; SOMATIC HYPERMUTATION; ANTIGEN SELECTION; GENE-EXPRESSION AB Analysis of clonotypic immunoglobulin M (IgM) from 15 patients with Waldenstrom macroglobulinemia (WM) showed a strong preferential use of the V(H)3/J(H)4 gene families. Identification of the WM IgM V/D/J was validated using single-cell analysis, confirming its presence in most B cells. Despite the extensive hypermutated V-H genes in 13 of 15 patients, statistical analysis of framework/complementary-determining region (FR/CDR) mutation patterns suggests that they might have escaped antigenic selection. Neither intraclonal diversity nor isotype switching was detectable. Membranous and secreted forms of clonotypic IgM transcripts were present in bone marrow and blood. Singlecell analysis showed that clonotypic B cells coexpress CD20, surface IgM (sIgM), and sIgD but that they lack CD138. Most B cells lacked memory marker CD27 despite their hypermutated variable regions otherwise suggestive of memory status. At diagnosis, circulating B cells in WM are largely clonotypic. However, when monoclonal IgM levels are decreased, clonotypic frequencies are substantially reduced despite elevated CD20(+) cells, shown to be polyclonal by DNA sequencing and CDR3 fragment analysis. Thus, WM includes the expansion of circulating, polyclonal B cells. Overall, this work suggests that WM may originate from a largely V(H)3-restricted, somatically mutated, predominantly CD27(-)IgM(+)IgD(+) population that cannot undergo class switching, suggestive of B cells that might have bypassed the germinal center. (C) 2004 by The American Society of Hematology. C1 Univ Alberta, Cross Canc Inst, Dept Med, Edmonton, AB, Canada. Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. RP Pilarski, LM (reprint author), Cross Canc Inst, Dept Oncol, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada. EM lpilarsk@ualberta.ca NR 46 TC 62 Z9 62 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2004 VL 104 IS 7 BP 2134 EP 2142 DI 10.1180/blood-2003-11-4024 PG 9 WC Hematology SC Hematology GA 857JP UT WOS:000224112800041 PM 14764523 ER PT J AU Huang, FW Rubio-Aliaga, I Kushner, JP Andrews, NC Fleming, MD AF Huang, FW Rubio-Aliaga, I Kushner, JP Andrews, NC Fleming, MD TI Identification of a novel mutation (C321X) in HJV SO BLOOD LA English DT Article ID HEMOCHROMATOSIS LOCUS MAPS; JUVENILE HEMOCHROMATOSIS; CHROMOSOME 1Q AB Juvenile hemochromatosis is a rare autosomal recessive disorder characterized by the early onset of severe iron overload. We report the occurrence of compound heterzygous mutatons in hemojuvelin (HJV), including a termination codon, in a patient with juvenile hemochromatosis but no family history of iron disorders. (C) 2004 by The American Society of Hematology. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Div Med Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. RP Fleming, MD (reprint author), Childrens Hosp, Dept Pathol, Enders 11,300 Longwood Ave, Boston, MA 02115 USA. EM mark.fleming@childrens.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 FU NCRR NIH HHS [RR00064]; NIDDK NIH HHS [R01 DK066373, R01 DK066373-01] NR 9 TC 31 Z9 36 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2004 VL 104 IS 7 BP 2176 EP 2177 DI 10.1182/blood-2004-01-0400 PG 2 WC Hematology SC Hematology GA 857JP UT WOS:000224112800047 PM 15138164 ER PT J AU Lee, SJ Joffe, S Kim, HT Socie, G Gilman, AL Wingard, JR Horowitz, MM Cella, D Syrjala, KL AF Lee, SJ Joffe, S Kim, HT Socie, G Gilman, AL Wingard, JR Horowitz, MM Cella, D Syrjala, KL TI Physicians' attitudes about quality-of-life issues in hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; CHRONIC MYELOID-LEUKEMIA; FOLLOW-UP; PSYCHOSOCIAL FACTORS; FUNCTIONAL STATUS; HEALTH; POPULATION; PATIENT; SATISFACTION AB Studies investigating quality of life (QOL) after hematopoietic stem cell transplantation demonstrate the spectrum of QOL outcomes awaiting survivors. Nevertheless, how transplantation physicians interpret and apply QOL information to clinical practice is poorly understood. We conducted a cross-sectional survey of transplantation physicians to address these issues and received 180 (24%) responses from physicians in 29 countries. Seventy-two percent reported that their patients are willing to accept poor QOL for a small chance of cure. Only 28% said that QOL considerations "often" or "almost all the time" enter into patients decisions about transplantation. This contrasted with physicians' reported attention to QOL in their discussions with patients. Although 53% of physicians reported using QOL results to modify practice, 55% would be more likely to use these data if they were more understandable. To ensure generalizability of the results, a validation sample was randomly selected, and these 85 physicians (response rate, 76%) confirmed the findings of the original survey. Given the extensive data regarding posttransplantation QOL, resources should be devoted to exploring how patients and physicians use these data in clinical care and in devising methods to ensure that QOL results are interpretable and relevant to patients and physicians. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Hop St Louis, APHP, Serv Greffe Moelle, Paris, France. Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Northwestern Univ, Dept Psychiat & Behav Sci, Evanston, IL USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephanie_lee@dfcl.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA096872, CA63030, CA78990] NR 51 TC 35 Z9 35 U1 2 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 OCT 1 PY 2004 VL 104 IS 7 BP 2194 EP 2200 DI 10.1182/blood-2003-07-2430 PG 7 WC Hematology SC Hematology GA 857JP UT WOS:000224112800052 PM 15198954 ER PT J AU McNeil, MR Hula, WD Matthews, CT Doyle, PJ Fossett, TRD AF McNeil, MR Hula, WD Matthews, CT Doyle, PJ Fossett, TRD TI Auditory comprehension and visual-manual tracking dual-task performance in aphasia: Preliminary findings SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID ATTENTION C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM mcneil@pitt.edu NR 10 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 OCT PY 2004 VL 91 IS 1 BP 31 EP 32 DI 10.1016/j.bandl.2004.06.019 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 861TZ UT WOS:000224442800014 ER PT J AU Caplan, D Waters, G DeDe, G Michaud, J Reddy, A AF Caplan, D Waters, G DeDe, G Michaud, J Reddy, A TI A study of syntactic processing in aphasia I: Behavioral (psycholinguistic) aspects SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Hlth Sci, Sargent Coll, Boston, MA 02215 USA. EM dcaplan@partners.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2004 VL 91 IS 1 BP 64 EP 65 DI 10.1016/j.bandl.2004.06.035 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 861TZ UT WOS:000224442800030 ER PT J AU Caplan, D Kennedy, D Alpert, N Makris, N Waters, G DeDe, G Michaud, J Reddy, A AF Caplan, D Kennedy, D Alpert, N Makris, N Waters, G DeDe, G Michaud, J Reddy, A TI A study of syntactic processing in aphasia II: Neurological aspects SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. Boston Univ, Sargent Coll, Dept Hlth Sci, Boston, MA 02215 USA. EM dcaplan@partners.org NR 1 TC 2 Z9 2 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 OCT PY 2004 VL 91 IS 1 BP 66 EP 67 DI 10.1016/j.bandl.2004.06.036 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 861TZ UT WOS:000224442800031 ER PT J AU Baudiffier, V Caplan, D Gaonac'h, D Gil, R AF Baudiffier, V Caplan, D Gaonac'h, D Gil, R TI A limit for a resource reduction theory of syntactic comprehension deficits: An auditory moving window investigation SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 CNRS, Lab Langage & Cognit, FRE 2725, F-86022 Poitiers, France. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Ctr Hosp Univ Poitiers, Serv Neurol & Neuropsychol & Reeducat Langage, Poitiers, France. EM vanessa.baudiffier@univ-poitiers.fr; dcaplan@partners.org; daniel.gaonach@mshs.univ-poitiers.fr; r.gil@chu-poitiers.fr NR 4 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2004 VL 91 IS 1 BP 112 EP 113 DI 10.1016/j.bandl.2004.06.058 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 861TZ UT WOS:000224442800054 ER PT J AU Mizoguchi, M Nutt, CL Mohapatra, G Louis, DN AF Mizoguchi, M Nutt, CL Mohapatra, G Louis, DN TI Genetic alterations of phosphoinositide 3-kinase subunit genes in human glioblastomas SO BRAIN PATHOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; REGULATORY SUBUNIT; PHOSPHATIDYLINOSITOL 3-KINASE; PROSTATE-CANCER; PTEN GENE; PATHWAY; ONCOGENE; TUMORS; PIK3CA; EXPRESSION AB Genetic alterations of PI3K (phosphoinositide 3-kinase) subunits have been documented in a number of tumor types, with increased PI3K activity linked to gene amplification and mutation of catalytic subunits, as well as mutations of regulatory subunits. Among high grade gliomas, activation of the PI3K-AKT signaling pathway through loss of PTEN function is common. We therefore investigated whether genetic alteration of class IA PI3Ks might provide a mechanism for deregulation of this pathway in glioblastomas. We studied a series of glioblastomas with FISH to assess copy number of catalytic subunits (PIKCA and PIK3CD) and with PCR-SSCP to screen for somatic mutations of conserved regions of both catalytic and regulatory subunits. FISH revealed frequent balanced copy number increases of both PIK3CA and PIK3CD, and one case showed an extra copy limited to PIK3CA. One glioblastoma exhibited a 9-bp deletion that encompassed the exon-intron junction of exon 12 of PIK3R1, documenting for the first time a mutation within a PI3K regulatory subunit in human glioblastoma. This deletion would be predicted to yield a truncated protein that lacks the inhibitory domain, resulting in increased PI3K activity. Furthermore, the case with selected PIK3CA copy number gain and the case with a truncating PIK3R1 mutation both featured AKT activation without PTEN mutation. These results suggest that genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 Thirteenth St, Charlestown, MA 02129 USA. EM dlouis@partners.org RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA 57683] NR 27 TC 99 Z9 104 U1 0 U2 1 PU INT SOC NEUROPATHOLOGY PI LOS ANGELES PA UCLA MEDICAL CENTER, SECTION NEUROPATHOLGY, C H S 18-126, LOS ANGELES, CA 90095-1732 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2004 VL 14 IS 4 BP 372 EP 377 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 871ZB UT WOS:000225174100005 PM 15605984 ER PT J AU Singh, I Paintlia, AS Khan, M Stanislaus, R Paintlia, MK Haq, E Singh, AK Contreras, MA AF Singh, I Paintlia, AS Khan, M Stanislaus, R Paintlia, MK Haq, E Singh, AK Contreras, MA TI Impaired peroxisomal function in the central nervous system with inflammatory disease of experimental autoimmune encephalomyelitis animals and protection by lovastatin treatment SO BRAIN RESEARCH LA English DT Article DE peroxisome; experimental autoimmune encephalomyelitis; statin; neuroinflammation ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; X-LINKED ADRENOLEUKODYSTROPHY; BETA-OXIDATION ENZYMES; RAT-LIVER PEROXISOMES; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; CHAIN FATTY-ACIDS; MULTIPLE-SCLEROSIS; LEWIS RATS; REDUCTASE INHIBITOR AB Peroxisomes are ubiquitous subcellular organelles and abnormality in their biogenesis and specific gene defects leads to fatal demyelinating disorders. We report that neuroinflammatory disease in brain of experimental autoimmune encephalomyelitis (EAE) rats decreased the peroxisomal functions. Degradation of very long chain fatty acids decreased by 47% and resulted in its accumulation (C26:0, 40%). Decreased activity (66% of control) of dihydroxyacetonephosphate acyltransferase (DHAP-AT), first enzyme in plasmalogens biosynthesis, resulted in decreased levels of plasmalogens (16-30%). Catalase activity, a peroxisomal enzyme, was also reduced (37%). Gene microarray analysis of EAE spinal cord showed significant decrease in transcripts encoding peroxisomal proteins including catalase (folds 3.2; p<0.001) and DHAP-AT (folds 2.6; p<0.001). These changes were confirmed by quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, suggesting that decrease of peroxisomal functions in the central nervous system will have negative consequences for myelin integrity and repair because these lipids are major constituents of myelin. However, lovastatin (a cholesterol lowering and anti-inflammatory drug) administered during EAE induction provided protection against loss/down-regulation of peroxisomal functions. Attenuation of induction of neuro inflammatory mediators by statins in cultured brain cells [J. Clin. Invest. 100 (1997) 2671-2679], and in central nervous system of EAE animals and thus the EAE disease [J. Neurosci. Res. 66 (2001) 155-162] and the studies described here indicate that inflammatory mediators have a marked negative effect on peroxisomal functions and thus on myelin assembly and that these effects can be prevented by treatment with statins. These observations are of importance because statins are presently being tested as therapeutic agents against a number of neuroinflammatory demyelinating diseases. (C) 2004 Elsevier B.V All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333; Haq, Ehtishamul/0000-0002-4195-0606 FU NINDS NIH HHS [NS 22576, NS 34741, NS 37766, NS 40144, NS 40810] NR 62 TC 41 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 1 PY 2004 VL 1022 IS 1-2 BP 1 EP 11 DI 10.1016/j.brainres.2004.06.059 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 856GL UT WOS:000224033600001 PM 15353207 ER PT J AU Gazda, HT Zhong, R Long, L Niewiadomska, E Lipton, JM Ploszynska, A Zaucha, JM Vlachos, A Atsidaftos, E Viskochil, DH Niemeyer, CM Meerpohl, JJ Rokicka-Milewska, R Pospisilova, D Wiktor-Jedrzejczak, W Nathan, DG Beggs, AH Sieff, CA AF Gazda, HT Zhong, R Long, L Niewiadomska, E Lipton, JM Ploszynska, A Zaucha, JM Vlachos, A Atsidaftos, E Viskochil, DH Niemeyer, CM Meerpohl, JJ Rokicka-Milewska, R Pospisilova, D Wiktor-Jedrzejczak, W Nathan, DG Beggs, AH Sieff, CA TI RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Diamond-Blackfan anaemia; haplo-insufficiency; RPS19 gene mutations ID GENETIC-HETEROGENEITY; WILLIAMS-SYNDROME; S19 GENE; IDENTIFICATION; EXPRESSION; POPULATION; REGION; LOCUS; PAX3 AB The genetic basis of Diamond-Blackfan anaemia (DBA), a congenital erythroid hypoplasia that shows marked clinical heterogeneity, remains obscure. However, the fact that nearly one-quarter of patients harbour a variety of mutations in RPS19, a ribosomal protein gene, provides an opportunity to examine whether haplo-insufficiency of RPS19 protein can be demonstrated in certain cases. To that end, we identified 19 of 81 DBA index cases, both familial and sporadic, with RPS19 mutations. We found 14 distinct insertions, deletions, missense, nonsense and splice site mutations in the 19 probands, and studied mutations in 10 patients at the RNA level and in three patients at the protein level. Characterization of the mutations in 10 probands, including six with novel insertions, nonsense and splice site mutations, showed that the abnormal transcript was detectable in nine cases. The RPS19 mRNA and protein in CD34(+) bone marrow cells identified haplo-insufficiency in three cases predicted to have one functional allele. Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. Childrens Hosp, Gen Program, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Med Sch, Dept Paediat Haematol Oncol, Warsaw, Poland. Schneider Childrens Hosp, Albert Einstein Coll Med, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY 11042 USA. Univ Med Sch, Dept Paediat Haematol & Oncol, Gdansk, Poland. Univ Med Sch, Dept Haematol, Gdansk, Poland. Univ Utah, Sch Med, Div Med Genet, Salt Lake City, UT USA. Univ Freiburg, Dept Paediat, Div Paediat Haematol & Oncol, Freiburg, Germany. Univ Hosp, Dept Paediat, Olomouc, Czech Republic. Med Univ Warsaw, Dept Haematol Oncol & Internal Dis, Warsaw, Poland. RP Gazda, HT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Rm M615,44 Binney St, Boston, MA 02115 USA. EM hanna_gazda@dfci.harvard.edu RI Meerpohl, Joerg/J-4224-2013; OI Meerpohl, Joerg/0000-0002-1333-5403; Beggs, Alan/0000-0001-8818-0568 FU NHLBI NIH HHS [R01 HL64775, HL99-021] NR 31 TC 76 Z9 78 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2004 VL 127 IS 1 BP 105 EP 113 DI 10.1111/j.1365-2141.2004.05152.x PG 9 WC Hematology SC Hematology GA 856FE UT WOS:000224030300013 PM 15384984 ER PT J AU Bauer, KA AF Bauer, KA TI Low intensity warfarin: is it clinically useful in venous thromboembolism management? SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE venous thromboembolism; deep venous thrombosis; anticoagulation; warfarin; clinical trials ID ORAL ANTICOAGULANT-THERAPY; LOW-DOSE WARFARIN; LONG-TERM; 1ST EPISODE; PREVENTION; RISK; THROMBOSIS; NO AB Therapy for a first episode of venous thromboembolism (VTE) typically includes a vitamin K antagonist, such as warfarin, for 3-6 months at an international normalized ratio (INR) of 2-3. After the cessation of warfarin therapy, unprovoked VTE is associated with a recurrence rate of 5-15% per year. Prolonging initial therapy does not reduce the recurrence risk once warfarin is discontinued and is not routinely recommended for such patients. The Prevention of Recurrent Venous Thromboembolism (PREVENT) and Extended Low-Intensity Anticoagulation for Thromboembolism (ELATE) trials were undertaken to evaluate the efficacy and safety of low-intensity warfarin (INR 5-2) in this population. While both trials demonstrated that low-intensity warfarin offers substantial protection against recurrent VTE, only the ELATE trial included a standard intensity arm; this arm showed a significantly lower recurrence rate and a major bleed rate that, surprisingly, was similar to the low-intensity arm. There still remains no consensus that long-term warfarin at an INR of 2-3 should be recommended for all patients who sustain a first unprovoked venous thromboembolic event, which largely stems from our current inability to reliably identify those patients most likely to develop recurrences. Given that an individualized approach is required in deciding the duration of anticoagulation, it is the author's belief that low-intensity warfarin, which the PREVENT trial demonstrated could be monitored every other month, is a useful option for some patients with a first episode of VTE. C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Bauer, KA (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kbauer@bidmc.harvard.edu NR 22 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2004 VL 127 IS 2 BP 155 EP 158 DI 10.1111/j.1365-2141.2004.05174.x PG 4 WC Hematology SC Hematology GA 859QT UT WOS:000224283700003 PM 15461620 ER PT J AU Jagannath, S Barlogie, B Berenson, J Siegel, D Irwin, D Richardson, PG Niesvizky, R Alexanian, R Limentani, SA Alsina, M Adams, J Kauffman, M Esseltine, DL Schenkein, DP Anderson, KC AF Jagannath, S Barlogie, B Berenson, J Siegel, D Irwin, D Richardson, PG Niesvizky, R Alexanian, R Limentani, SA Alsina, M Adams, J Kauffman, M Esseltine, DL Schenkein, DP Anderson, KC TI A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; myeloma; relapsed; refractory; dexamethasone ID PROTEASOME INHIBITOR PS-341; MULTIPLE-MYELOMA; I TRIAL; MALIGNANCIES; THALIDOMIDE; APOPTOSIS; THERAPY; PATHWAY; GROWTH AB In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy. C1 St Vincents Catholic Med Ctr, New York, NY USA. Univ Arkansas, Little Rock, AR 72204 USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Hackensack Univ Med Ctr, Hackensack, NJ USA. Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Carolinas Hematol Oncol Associates, Charlotte, NC USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Infin Pharmaceut Inc, Cambridge, MA USA. Predix Pharmaceut Inc, Woburn, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Jagannath, S (reprint author), St Vincents Comprehens Canc Ctr, 325 W 15th St, New York, NY 10011 USA. EM sjaganna@salick.com NR 16 TC 486 Z9 513 U1 0 U2 12 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2004 VL 127 IS 2 BP 165 EP 172 DI 10.1111/j.1365-2141.2004.05188.x PG 8 WC Hematology SC Hematology GA 859QT UT WOS:000224283700005 PM 15461622 ER PT J AU Chen, WY Hankinson, SE Schnitt, SJ Rosner, BA Holmes, MD Colditz, GA AF Chen, WY Hankinson, SE Schnitt, SJ Rosner, BA Holmes, MD Colditz, GA TI Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma 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 breast carcinoma; hormone replacement therapy; epidemiology; estrogen receptor; progesterone receptor ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; GENE-EXPRESSION PATTERNS; CANCER RISK; PLUS PROGESTIN; PROGNOSTIC CHARACTERISTICS; AGE; REPRODUCIBILITY; AGGRESSIVENESS; HISTOLOGY AB BACKGROUND. Observational studies and randomized trials have demonstrated that hormone replacement therapy (HRT) increases the recipient's risk of developing breast carcinoma. Because it is known that some breast malignancies are hormonally responsive and that others are not, it has been hypothesized that HRT may be associated with the development of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive breast carcinoma more so than with the development of ER-negative/PR-negative breast carcinoma. METHODS. The Nurses' Health Study is a prospective cohort study that enrolled 121,700 female registered nurses ages 30-55 years in 1976. In the current study, the authors analyzed 2548 malignancies that developed among eligible postmenopausal women in that cohort between 1980 and 2000 and for which data on ER and PR status were available. RESULTS. Compared with women who had never used HRT, current long-term users of HRT were more likely to develop ER-positive/PR-positive breast carcinoma (multivariate risk ratio [RR], 1.80; 95% confidence interval [CI], 1.52-2.12) but were not any more likely to develop ER-negative/PR-negative disease (multivariate RR, 1.00; 95% Cl, 0.72-1.39). This effect grew stronger with increasing duration of current HRT use and was also more pronounced among women with body mass index < 25 kg/m(2). Furthermore, the association between HRT use and ER-positive/PR-positive disease was stronger among patients receiving combined HRT (CHRT) regimens, which included estrogen and progesterone, than among users of estrogen alone (ERT). In addition, tumors tended to develop more quickly in current users of CHRT than in ERT users. CONCLUSIONS. The finding that current users of HRT were more likely to develop ER-positive/PR-positive tumors than they were to develop ER-negative/PR-negative ones suggests that both endogenous and exogenous hormonal factors may influence breast tumor characteristics. In analyses of the effects of hormonal factors on breast tumor development, ER-positive/PR-positive tumors and ER-negative/PR-negative tumors should be considered separately from each other. (C) 2004 American Cancer Society. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Chen, WY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM wychen@partners.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA087969, CA089393] NR 44 TC 88 Z9 94 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 OCT 1 PY 2004 VL 101 IS 7 BP 1490 EP 1500 DI 10.1002/cncr.20499 PG 11 WC Oncology SC Oncology GA 855RV UT WOS:000223992300003 PM 15378477 ER PT J AU Smith, MR Manola, J Kaufman, DS George, D Oh, WK Mueller, E Slovin, S Spiegelman, B Small, E Kantoff, PW AF Smith, MR Manola, J Kaufman, DS George, D Oh, WK Mueller, E Slovin, S Spiegelman, B Small, E Kantoff, PW TI Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy 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 prostate carcinoma; prostate-specific antigen; peroxisome proliferator activated receptor gamma; rosiglitazone ID ACTIVATED RECEPTOR-GAMMA; CANCER; LIGAND; PROGRESSION; KINETICS; TRIALS; PSA AB BACKGROUND. The objective of this study was to assess the biologic activity of rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist that has been approved to treat type 2 diabetes, in men with recurrent prostate carcinoma using change in prostate specific antigen (PSA) doubling time (PSADT) as the primary outcome variable. METHODS. Men with histologically confirmed prostate carcinoma, no recent hormone therapy, a rising serum PSA level after radical prostatectomy and/or radiation therapy, and no radiographic evidence of metastases were assigned randomly to receive either oral rosiglitazone (4 mg twice daily) or placebo. The treatment was continued until the men developed disease progression or adverse effects. A positive outcome was defined as a posttreatment PSADT > 150% the baseline PSADT and no new metastases. RESULTS. One hundred six men were enrolled. The median treatment duration was 315 days for men in the placebo group and 338 days for men in the rosiglitazone group (P = 0.28). Forty percent of men in the in the placebo group and 38% of men in the rosiglitazone group had a posttreatment PSADT > 150% of the baseline PSADT and no new metastases (P = 1.00). In exploratory analyses, the rate of a positive outcome remained higher than expected in the placebo group, even when a positive outcome was redefined using more stringent criteria. The time to disease progression was similar between the groups. CONCLUSIONS. Rosiglitazone did not increase PSADT or prolong the time to disease progression more than placebo in men with a rising PSA level after radical prostatectomy and/or radiation therapy. The unexpected discordance between baseline and posttreatment PSADT in the placebo group reinforced the importance of randomized controlled trials in this setting. (C) 2004 American Cancer Society. C1 Massachusetts Gen Hosp, Div Hematol & Med Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol & Med Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [5 P50 CA90381-02] NR 16 TC 84 Z9 87 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 OCT 1 PY 2004 VL 101 IS 7 BP 1569 EP 1574 DI 10.1002/cncr.20493 PG 6 WC Oncology SC Oncology GA 855RV UT WOS:000223992300013 PM 15468186 ER PT J AU Arnold, CN Goel, A Niediwiecki, D Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR AF Arnold, CN Goel, A Niediwiecki, D Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR TI APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q SO CANCER BIOLOGY & THERAPY LA English DT Article DE colorectal cancer (CRC); adenomatous polyposis coli (APC); loss of heterozygosity (LOH); immunohistochemistry (IHC) ID BETA-CATENIN; MICROSATELLITE INSTABILITY; DNA METHYLATION; COLON-CANCER; MUTATIONS; PROGRESSION; PATTERNS; PATHWAY; TARGET; GENES AB Introduction: Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promoter influences APC silencing. Here we examined the influence of APC methylation on APC expression in tumors with and without LOH at the APC locus. Material and Methods: 137 sporadic colorectal cancer specimens were investigated for LOH at the 5q locus. The methylation status of the APC promoter was determined by methylation-specific PCR. APC expression was performed by immunohistochemistry. Results: expression was reduced or lost in 110 of 137 (80%) tumors and LOH at 5q was found in 13 of 132 (10%) tumors. There was no difference in 5q LOH between tumors with or without intact APC expression. Vice versa, there was no difference in the APC expression in tumors with 5q LOH. Aberrant APC promoter methylation was detected in 33 of 118 (28%) tumors investigated. Of the tumors with 5q LOH for which methylation data were available, 4 of 11 (36%) were methylated versus 28 of 105 (27%) of those without LOH. No difference in methylation was observed in tumors without 5q LOH and normal APC expression and those without 5q LOH and reduced or missing APC expression. Importantly, none of the tumors with 5q LOH and normal APC staining were aberrantly methylated, whereas 50% of the cancers with LOH at 5q and reduced or absent staining were hypermethylated. Conclusions: This report suggests that tumors with 5q LOH and reduced APC expression are more frequently hypermethylated at the APC promoter compared to those tumors with 5q LOH and normal APC expression. The association among APC promoter methylation status, 5q LOH, and reduced or lost APC expression suggests that de novo methylation plays an important role as a "second hit" in silencing APC expression in colorectal neoplasia. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Comprehens Canc, La Jolla, CA 92093 USA. Duke Univ, CAlGB Stat Ctr, Durham, NC USA. San Diego Vet Affairs Medc Ctr, La Jolla, CA USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Boland, CR (reprint author), Baylor Univ, Med Ctr, Dept Gastroenterol, 2 Hoblitzelle,3500 Gaston Ave, Dallas, TX 75246 USA. EM rickbo@boylorhealth.edu FU NCI NIH HHS [R01-CA 72851, CA-31946] NR 28 TC 52 Z9 55 U1 0 U2 2 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 OCT PY 2004 VL 3 IS 10 BP 960 EP 964 PG 5 WC Oncology SC Oncology GA 903QI UT WOS:000227440300016 PM 15326380 ER PT J AU Hussein, MR Hassan, HI AF Hussein, MR Hassan, HI TI Alterations of p53, Bcl-2, and hMSH2 protein expression in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas in the Upper Egypt SO CANCER BIOLOGY & THERAPY LA English DT Article DE p53; Bcl-2; hMSH2; breast cancer ID RADIAL GROWTH-PHASE; CUTANEOUS MALIGNANT MELANOMAS; ULTRAVIOLET-B IRRADIATION; TUMOR-SUPPRESSOR GENE; MICROSATELLITE INSTABILITY; OVARIAN-CANCER; IMMUNOHISTOCHEMICAL EXPRESSION; CELL-LINES; MUTATIONS; ACCUMULATION AB Background: Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (Bcl-2) and housekeeping genes [human MutS homologue-2 (hMSH2)]. We hypothesized that mammary carcinogenesis involves interactions among p53, Bcl-2 and hMSh2 proteins. In the Upper Egypt, the clinicopathologic features and genetic changes during mammary carcinogenesis are unknown. Methods: To test our hypothesis and to examine these issues, 53 mastectomy specimens, each entailing normal breast, benign proliferative breast disease (BPBD), duct carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were immunostained for p53, Bcl-2 and hMSH2 protein expression. Results: The average age incidence of ductal carcinomas was 43.2 +/- 7.06 years. The tumors were common in the left than right side (1.2:1, respectively, p > 0.05). Infiltrating ductal carcinoma of non-specific type was the most common histologic type. Examination of the average weighted scores in the normal breast, BPBD, DCIS and IDC, respectively, showed: (1) significant upregulation of p53 proteins (0.00 +/- 0.00, 0.00 +/- 0.00, 6.25 +/- 2.42, 6.62 +/- 2.15, p = 0.001), (2) insignificant downregulation of Bcl-2 (6.67 +/- 1.33, 5.17 +/- 2.20, 4.79 +/- 2.27 and 4.42 +/- 2.83, p = 0.37), and (3) significant downregulotion of hMSH2 (11.3 +/- 0.75, 10.70 +/- 1.27, 7.11 +/- 1.50 and 7.0 +/- 1.33, p = 0.0006). There were insignificant negative correlations between p53 and both Bcl-2 (r = -0.20, p > 0.05) and hMSH2 (r = -0.15, p > 0.05) protein expression. Conclusions: In the Upper Egypt: (1) breast cancer had similar clinicopathologic features to those in the high risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during mammary carcinogenesis. C1 Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. EM mrh17@swissinfo.org NR 35 TC 17 Z9 18 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 OCT PY 2004 VL 3 IS 10 BP 983 EP 988 PG 6 WC Oncology SC Oncology GA 903QI UT WOS:000227440300021 PM 15467428 ER PT J AU Argilla, D Chin, K Singh, M Hodgson, JG Bosenberg, M de Solorzano, CO Lockett, S DePinho, RA Gray, J Hanahan, D AF Argilla, D Chin, K Singh, M Hodgson, JG Bosenberg, M de Solorzano, CO Lockett, S DePinho, RA Gray, J Hanahan, D TI Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes SO CANCER CELL LA English DT Article ID MULTISTAGE TUMORIGENESIS; CELL-PROLIFERATION; LACKING TELOMERASE; HUMAN FIBROBLASTS; TISSUE-SECTIONS; TRANSGENIC MICE; DEFICIENT MICE; IMMORTAL CELLS; CANCER; LENGTH AB The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence of telomerase had minimal impact on tumorigenesis, even in terc(-/-) generations (G5-7) exhibiting shortened telomeres and phenotypic abnormalities in multiple organs. Analyses of chromosomal aberrations were not indicative of telomere dysfunction or increased genomic instability in tumors. Quantitative image analysis of telomere repeat intensities comparing biopsies of skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and relative lengths were maintained during progression, implicating a means for preserving telomere repeats and functionality in the absence of telomerase. C1 Univ Calif San Francisco, Ctr Diabet, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Hanahan, D (reprint author), Univ Calif San Francisco, Ctr Diabet, Dept Biochem & Biophys, San Francisco, CA 94143 USA. EM dh@biochem.ucsf.edu RI Ortiz de Solorzano, Carlos/G-3278-2010 OI Ortiz de Solorzano, Carlos/0000-0001-8720-0205 NR 54 TC 15 Z9 15 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2004 VL 6 IS 4 BP 373 EP 385 DI 10.1016/j.ccr.2004.08.032 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 865HO UT WOS:000224693500009 PM 15488760 ER PT J AU Kazhdan, I Marciniak, RA AF Kazhdan, I Marciniak, RA TI Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) SO CANCER GENE THERAPY LA English DT Article DE breast cancer; death receptor 4; tumor targeting; hTERT promoter ID NF-KAPPA-B; REVERSE-TRANSCRIPTASE PROMOTER; C-FLIP EXPRESSION; PROSTATE-CANCER; MEDIATED APOPTOSIS; DEATH RECEPTOR; DECOY RECEPTORS; DOWN-REGULATION; GENE-THERAPY; GLIOMA-CELLS AB Breast cancer cells are generally resistant to induction of apoptosis by treatment with tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL). In this study, we demonstrate that both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor, death receptor 4 (DR4). The extent of cell death depended on the strength of the promoter driving DR4 expression. When driven by the strong CMV promoter, expression of DR4 killed over 90% of cells in five out of six cell lines tested in the absence of exogenous TRAIL. When driven by the relatively weak tumor-specific hTERT promoter, DR4 was less effective alone, but sensitized cells to killing by TRAIL. The extent of TRAIL sensitization depended on the magnitude of hTERT promoter activity. MCF-7 cells were relatively resistant to the action of DR4. We compared expression of the genes involved in transduction and execution of the death receptor-initiated apoptotic stimuli between MCF-7 and DR4-sensitive cell lines. We confirmed that in the panel of cell lines, MCF-7 was the only line deficient in expression of caspase 3. Bcl-2 and FLIP proteins, implicated in suppression of TRAIL-induced apoptosis, were expressed at a higher level. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kazhdan, I (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kazhdan@uthscsa.edu FU NCI NIH HHS [5 K12 CA01723-10] NR 40 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD OCT PY 2004 VL 11 IS 10 BP 691 EP 698 DI 10.1038/sj.cgt.7700747 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 857CA UT WOS:000224091900004 PM 15354201 ER PT J AU Selander, KS Li, L Watson, L Merrell, M Dahmen, H Heinrich, PC Muller-Newen, G Harris, KW AF Selander, KS Li, L Watson, L Merrell, M Dahmen, H Heinrich, PC Muller-Newen, G Harris, KW TI Inhibition of gp130 signaling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR; TISSUE INHIBITOR; CARCINOMA-CELLS; EGF RECEPTOR; INTERLEUKIN-6 RECEPTOR; EXPRESSION; PROTEIN; FAMILY; SRC; LINES AB The cytokine receptor gp130 is the common signaling subunit of receptors used by the interleukin (IL)-6 cytokine family. gp130 is widely expressed in breast cancer cell lines and primary tumors. The role of gp130 in breast cancer in vivo is unknown. To study the effect of gp130 inhibition in breast cancer, endogenous gp130 signaling in breast cancer cell lines was blocked with a dominant-negative gp130 protein (DN gp130). DN gp130 inhibited constitutive Stat3 activation in breast cancer cells. Both gp130 and epidermal growth factor receptor (EGFR) have been implicated in constitutive Stat3 activation in breast cancer. There are known physical and functional interactions between gp130 and EGFR. Consistent with this, we show that DN gp130 inhibits signaling downstream of the EGFR in breast cancer cells. The effect of DN gp130 on breast cancer in vivo was assessed with an orthotopic nude mouse model. DN gp130 MDA-231 cells had markedly decreased engraftment, size, and metastasis compared with control cells. These results are particularly striking considering that DN gp130-expressing breast cancer cells grow faster in vitro. We hypothesized that DN gp130 expression results in inhibition of invasion and metastasis in vivo. Marked angiogenesis was present in tumors from control animals and was absent in tumors from DN gp130 animals. We additionally show that tissue inhibitor of metalloproteinase-3, an inhibitor of tumor invasion and angiogenesis, is up-regulated in both MDA-231 DN gp130 cells and tumors. These results, in light of the availability of several potential pharmacological inhibitors of gp130, suggest novel approaches to breast cancer therapy. C1 Univ Alabama, Div Hematol Oncol, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Rhein Westfal TH Aachen, Inst Biochem, Aachen, Germany. RP Harris, KW (reprint author), Univ Alabama, Div Hematol Oncol, Dept Med, WTI 520-D,1530 3rd Ave S, Birmingham, AL 35294 USA. EM kevin.harris@ccc.uab.edu NR 40 TC 54 Z9 56 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 OCT 1 PY 2004 VL 64 IS 19 BP 6924 EP 6933 DI 10.1158/0008-5472.CAN-03-2516 PG 10 WC Oncology SC Oncology GA 859UC UT WOS:000224292400016 PM 15466183 ER PT J AU Moreno, CS Ramachandran, S Ashby, DG Laycock, N Plattner, CA Chen, W Hahn, WC Pallas, DC AF Moreno, CS Ramachandran, S Ashby, DG Laycock, N Plattner, CA Chen, W Hahn, WC Pallas, DC TI Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56 gamma knockdown SO CANCER RESEARCH LA English DT Article ID SMALL-T-ANTIGEN; PROTEIN PHOSPHATASE 2A; SV40 SMALL-T; NF-KAPPA-B; ANCHORAGE-INDEPENDENT GROWTH; PHOSPHATIDYLINOSITOL 3-KINASE; ONCOGENIC TRANSFORMATION; EPITHELIAL-CELLS; CYCLIN-A; S-PHASE AB One set of genes sufficient for transformation of primary human cells uses the combination of Ha-Ras-V12, the telomerase catalytic subunit hTERT, SV40 large tumor antigen (LT), and SV40 small tumor antigen (ST). Whereas SV40 LT inactivates the retinoblastoma protein and p53, the contribution of ST is poorly understood. The essential helper function of ST requires a functional interaction with protein phosphatase 2A (PP2A). Here we have identified changes in gene expression induced by ST and show that ST mediates these changes through both MA-dependent and MA-independent mechanisms. Knockdown of MA B56gamma subunit can substitute for ST expression to fully transform cells expressing LT, hTERT, and Ras-V12. We also identify those genes affected similarly in two cell lines that have been fully transformed from a common parental line by two alternative mechanisms, namely ST expression or PP2A B56gamma subunit knockdown. ST altered expression of genes involved in proliferation, apoptosis, integrin signaling, development, immune responses, and transcriptional regulation. ST reduced surface expression of MHC class I molecules, consistent with a need for SV40 to evade immune detection. ST expression enabled cell cycle progression in reduced serum and src phosphorylation in anchorage-independent media, whereas B56gamma knockdown required normal serum levels for these phenotypes. Inhibitors of integrin and src signaling prevented anchorage-independent growth of transformed cells, suggesting that integrin and src activation are key ST-mediated events in transformation. Our data support a model in which ST promotes survival through constitutive integrin signaling, src phosphorylation, and nuclear factor kappaB activation, while inhibiting cell-cell adhesion pathways. C1 Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. Emory Univ, Sch Med, Dept Biochem, Atlanta, GA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Broad Inst, Cambridge, MA USA. RP Moreno, CS (reprint author), Emory Univ, Dept Pathol & Lab Med, Whitehead Room 105J,615 Michael St, Atlanta, GA 30322 USA. EM cmoreno@emory.edu; dpallas@emory.edu RI Moreno, Carlos/B-3863-2009 OI Moreno, Carlos/0000-0002-5582-0028 FU NCI NIH HHS [K01 CA94223, CA57327, K22 CA96560, P01 CA50661, R01 CA057327] NR 59 TC 38 Z9 40 U1 1 U2 6 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 OCT 1 PY 2004 VL 64 IS 19 BP 6978 EP 6988 DI 10.1158/0008-5472.CAN-04-1150 PG 11 WC Oncology SC Oncology GA 859UC UT WOS:000224292400023 PM 15466190 ER PT J AU Wang, HY Wang, HC Powell, SN Iliakis, G Wang, Y AF Wang, HY Wang, HC Powell, SN Iliakis, G Wang, Y TI ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining SO CANCER RESEARCH LA English DT Article ID STRAND BREAK REPAIR; DNA-DAMAGE CHECKPOINT; IONIZING-RADIATION; S-PHASE; DIRECTED REPAIR; MAMMALIAN-CELLS; CHK1 PATHWAY; CYCLE; KINASE; PHOSPHORYLATION AB ATR is one of the most important checkpoint proteins in mammalian cells responding to DNA damage. Cells defective in normal ATR activity are sensitive to ionizing radiation (IR). The mechanism by which ATR protects the cells from IR-induced killing remains unclear. DNA double-strand breaks (DSBs) induced by IR are critical lesions for cell survival. Two major DNA DSB repair pathways exist in mammalian cells: homologous recombination repair (HRR) and nonhomologous end joining (NHEJ). We show that the doxycycline (dox)-induced ATR kinase dead (ATRkd) cells have the similar inductions and rejoining rates of DNA DSBs compared with cells without dox induction, although the dox-induced ATRkd cells are more sensitive to IR and have the deficient S and G(2) checkpoints. We also show that the dox-induced ATRkd cells have a lower HRR efficiency compared with the cells without dox induction. These results indicate that the effects of ATR on cell radiosensitivity are independent of NHEJ but are linked to HRR that may be affected by the deficient S and G(2) checkpoints. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Jefferson Med Coll, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Lab Mol & Cellular Radiat Biol, Charlestown, MA USA. Univ Duisburg Gesamthsch, Sch Med, Inst Med Radiat Biol, Essen, Germany. RP Wang, Y (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Jefferson Med Coll, Dept Radiat Oncol, Thompson Bldg,B-1,1020 Sansom St, Philadelphia, PA 19107 USA. EM ya.wang@mail.tju.edu FU NCI NIH HHS [P30-CA56036, T32-CA09137] NR 35 TC 82 Z9 83 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 OCT 1 PY 2004 VL 64 IS 19 BP 7139 EP 7143 DI 10.1158/0008-5472.CAN-04-1289 PG 5 WC Oncology SC Oncology GA 859UC UT WOS:000224292400044 PM 15466211 ER PT J AU Unni, E Sun, SH Nan, BC McPhaul, MJ Cheskis, B Mancini, MA Marcelli, M AF Unni, E Sun, SH Nan, BC McPhaul, MJ Cheskis, B Mancini, MA Marcelli, M TI Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; MEMBRANE PROGESTIN RECEPTOR; EPIDERMAL-GROWTH-FACTOR; PROTEIN-KINASE; PHOSPHORYLATION SITES; ESTROGEN-RECEPTOR; TYROSINE KINASE; CARCINOMA-CELLS; MAMMARY-TUMORS; SEX STEROIDS AB A cure for prostate cancer (CaP) will be possible only after a complete understanding of the mechanisms causing this disease to progress from androgen dependence to androgen independence. To carry on a careful characterization of the phenotypes of CaP cell lines before and after acquisition of androgen independence, we used two human CaP LNCaP sublines: LNCaPnan, which is androgen dependent (AD), and LNCaP-HP, which is androgen independent (AI). In AD LNCaPnan cells, dihydrotestosterone (DHT) stimulated in an androgen receptor (AR)-dependent way a phosphorylation signaling pathway involving steroid receptor coactivator (Src)-mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)-1/2-ERK-1/2-cAMP-response element binding-protein (CREB). Activation of this pathway was associated with increased [H-3]thymidine incorporation and resistance to apoptosis. Use of dominant-negative forms of MEK-1/2 and CREB demonstrated in LNCap(nan) cells that DHT induced [H-3]thymidiine incorporation through a thus far unidentified molecule activated downstream of NIEK-1/2, and antiapoptosis through phosphorylation of the transcription factor CREB. In contrast, in AI LNCaP-HP cells, the Src-MEK-1/2-ERK-1/2-CREB pathway was constitutively active. Because it was not further stimulated by addition of DHT, no increase of [3 H]thymidine incorporation or apoptosis resistance was demonstrated in LNCaP-HP cells. Additional experiments showed that Src and the scaffold protein MNAR coimmunoprecipitated with AR, indicating a role for Src as an apical molecule in the Sre-MEK-1/2-ERK-1/2-CREB pathway. Interestingly, differences between the two cell lines were that in LNCaP-HP cells presence of an AI phenotype and lack of response to DHT were associated with constitutive activation of the protein kinase Src and interaction among Src, AR, and MNAR. In contrast, in LNCaPnan cells, presence of an AD phenotype and ability to respond to DHT were associated with DHT-dependent activation of Src kinase activity and interaction among Src, AR, and MNAR. Intriguingly, in LNCaPnan cells, we found that transcription through the prototypical CREB-responsive promoter c-fos could be induced in a DHT-dependent way, and this action was inhibited by the AR antagonist Casodex and MEK-1 inhibitor PD98059. In contrast, transcription through the PSA P/E promoter, a prototypical AR-dependent promoter directly activated by agonist, was obliterated only by Casodex. Additional experiments with genital skin fibroblasts derived from patients with a variety of AR abnormalities indicated that nongenotropic AR signaling does not depend on an intact DNA-binding domain or on the ability of AR to translocate to the nucleus. The results suggest the following: (1) Constitutive activation of the Src-MEK-1/2-ERK-1/2-CREB pathway is associated with the AI phenotype observed in LNCaP-HP cells. (2) Activation of the Src-MEK-1/2-ERK-1/2-CREB pathway is DHT dependent in AD LNCaPnan cells. (3) DHT activation of this pathway is associated with induction of [H-3]thymidine incorporation by a molecule activated downstream of MEK-1/2 and of antiapoptosis through activation of the transcription factor CREB in AD LNCaPnan cells. (4) AR regulates transcription either directly upon ligand binding and nuclear translocation or indirectly through kinase pathways leading to activation of downstream transcription factors. (5) Nuclear translocation and ability of the DNA-binding domain of AR to interact with DNA are not prerequisites for nongenotropic AR activity. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Wyeth Pharmaceut, Womens Hlth Res Inst, Dept Cell Biol, Collegeville, PA USA. RP Marcelli, M (reprint author), 2002 Holcombe Blvd, Houston, TX 77030 USA. EM marcelli@bcm.tmc.edu FU NIDDK NIH HHS [DK03892, DK 55622] NR 70 TC 162 Z9 168 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2004 VL 64 IS 19 BP 7156 EP 7168 DI 10.1158/0008-5472.CAN-04-1121 PG 13 WC Oncology SC Oncology GA 859UC UT WOS:000224292400047 PM 15466214 ER PT J AU Lin, JD Wu, PH Tarr, PT Lindenberg, KS St-Pierre, J Zhang, CY Mootha, VK Jager, S Vianna, CR Reznick, RM Cui, LB Manieri, M Donovan, MX Wu, ZD Cooper, MP Fan, MC Rohas, LM Zavacki, AM Cinti, S Shulman, GI Lowell, BB Krainc, D Spiegelman, BM AF Lin, JD Wu, PH Tarr, PT Lindenberg, KS St-Pierre, J Zhang, CY Mootha, VK Jager, S Vianna, CR Reznick, RM Cui, LB Manieri, M Donovan, MX Wu, ZD Cooper, MP Fan, MC Rohas, LM Zavacki, AM Cinti, S Shulman, GI Lowell, BB Krainc, D Spiegelman, BM TI Defects in adaptive energy metabolism with CNS-Linked hyperactivity in PGC-1 alpha null mice SO CELL LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; CONTROLLING MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL COACTIVATOR PGC-1; INSULIN-RESISTANCE; HEPATIC GLUCONEOGENESIS; UNCOUPLING PROTEIN; GLUCOSE-PRODUCTION; BINDING-PROTEIN; TRANSGENIC MICE; CDNA CLONING AB PGC-1alpha is a coactivator of nuclear receptors and other transcription factors that regulates several metabolic processes, including mitochondrial biogenesis and respiration, hepatic gluconeogenesis, and muscle fiber-type switching. We show here that, while hepatocytes lacking PGC-1alpha are defective in the program of hormone-stimulated gluconeogenesis, the mice have constitutively activated gluconeogenic gene expression that is completely insensitive to normal feeding controls. C/EBPbeta is elevated in the livers of these mice and activates the gluconeogenic genes in a PGC-1alpha-independent manner. Despite having reduced mitochondrial function, PGC-1alpha null mice are paradoxically lean and resistant to diet-induced obesity. This is largely due to a profound hyperactivity displayed by the null animals and is associated with lesions in the striatal region of the brain that controls movement. These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mass Gen Inst Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06520 USA. Univ Ancona, Fac Med, Inst Normal Human Morphol, I-60020 Ancona, Italy. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI vianna, claudia /I-4991-2012 FU NIDDK NIH HHS [DK40936, DK065584, DK54477, DK61562, R01 DK040936]; NINDS NIH HHS [NS002174, NS045242] NR 46 TC 669 Z9 684 U1 11 U2 37 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 2004 VL 119 IS 1 BP 121 EP + DI 10.1016/j.cell.2004.09.013 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 859UE UT WOS:000224292600014 PM 15454086 ER PT J AU Le Gouill, S Podar, K Harousseau, JL Anderson, KC AF Le Gouill, S Podar, K Harousseau, JL Anderson, KC TI Mcl-1 regulation and its role in multiple myeloma SO CELL CYCLE LA English DT Article DE Mcl-1; regulation; multiple myeloma ID ENDOTHELIAL GROWTH-FACTOR; CELL-DEATH; BCL-2 FAMILY; SURVIVAL; PROTEIN; APOPTOSIS; INTERLEUKIN-6; KINASE; DIFFERENTIATION; ACTIVATION AB Among the Bcl-2 family, myeloid cell leukemia-1 (Mcl-1) distinguishes itself from the other pro-survival proteins by its ability to oppose to a wide variety of pro-apoptotic stimuli, short half-life, and presence of polypeptide sequences enriched in proline ( P), glutamic acid ( E), serine ( S) and threonine ( T) domains ( PEST). Moreover, Mcl-1 undergoes a complex transcriptional, post-transcriptional, and post-translational regulation process. This regulation modifies not only Mcl-1 expression, but also its function. Various extracellular stimuli, including cytokines, growth factors, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and IFN, activate pathways which regulate Mcl-1 expression. Furthermore, Mcl-1 can be alternatively spliced into a long (Mcl-1) or a short (Mcl-1S) form. Mcl-1 opposes pro-apoptotic proteins and can be either cleaved or phosphorylated at a post-translational level. Mcl-1-spliced products, Mcl-1-cleaved products, or phosphorylated Mcl-1 have either a pro or an anti-apoptotic function, highlighting the complexity and pivotal role of Mcl-1 regulation. Here we discuss the regulation and function of Mcl-1 in the pathophysiology of multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. CHU Nantes, Hotel Dieu, Serv Hematol Clin, Nantes 01, France. CHU Nantes, Hotel Dieu, Inst Biol, INSERM,U0601, Nantes 01, France. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. EM Kenneth_anderson@dfci.harvard.edu NR 36 TC 71 Z9 73 U1 1 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT PY 2004 VL 3 IS 10 BP 1259 EP 1262 PG 4 WC Cell Biology SC Cell Biology GA 877SP UT WOS:000225590800014 PM 15467463 ER PT J AU Senecal, EL Nelson, BP Biese, K Thomas, SH AF Senecal, EL Nelson, BP Biese, K Thomas, SH TI Chest pain display facilitates physician monitoring of patients' pain in the Emergency Department SO CHEST LA English DT Meeting Abstract CT CHEST 2004 Conference CY OCT 23-28, 2004 CL Seattle, WA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 OCT PY 2004 VL 126 IS 4 SU S BP 794S EP 794S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 865VF UT WOS:000224731400280 ER PT J AU Nield, M Hoo, GS Roper, J Santiago, S AF Nield, M Hoo, GS Roper, J Santiago, S TI Pursed-lips breathing decreases dyspnea and improves health-related quality of life in 4-group randomized, controlled study SO CHEST LA English DT Meeting Abstract CT CHEST 2004 Conference CY OCT 23-28, 2004 CL Seattle, WA C1 W LA VA, VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 2 Z9 2 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 OCT PY 2004 VL 126 IS 4 SU S BP 805S EP 805S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 865VF UT WOS:000224731400315 ER PT J AU Aronson, AA Thomas, SH Harrison, T Saia, M Bach, H AF Aronson, AA Thomas, SH Harrison, T Saia, M Bach, H TI Use of end-tidal carbon dioxide monitoring to detect occult hypoventilation in patients receiving opioids in the pre-hospital and emergency department settings SO CHEST LA English DT Meeting Abstract CT CHEST 2004 Conference CY OCT 23-28, 2004 CL Seattle, WA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2004 VL 126 IS 4 SU S BP 907S EP 907S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 865VF UT WOS:000224731400624 ER PT J AU Lock, BJ Dransfield, MT AF Lock, BJ Dransfield, MT TI Factors influencing the rate of lung cancer resection in a veteran population SO CHEST LA English DT Meeting Abstract CT CHEST 2004 Conference CY OCT 23-28, 2004 CL Seattle, WA C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. 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 OCT PY 2004 VL 126 IS 4 SU S BP 913S EP 914S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 865VF UT WOS:000224731400647 ER PT J AU Shang, H Han, XX Wang, YN Zhou, LP Zhang, ZN Jiang, YJ Zhang, M Yu, X AF Shang, H Han, XX Wang, YN Zhou, LP Zhang, ZN Jiang, YJ Zhang, M Yu, X TI Specific cytotoxic T lymphocyte responses in Chinese HIV/AIDS patients SO CHINESE MEDICAL JOURNAL LA English DT Article DE HIV-1; T-lymphocytes, cytotoxic; HIV-1 Gag ID HIV-1 INFECTION C1 China Med Univ, Affiliated Hosp 1, AIDS Res Ctr, Shenyang 110001, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Infect Dis Div, Boston, MA 02129 USA. RP Shang, H (reprint author), China Med Univ, Affiliated Hosp 1, AIDS Res Ctr, Shenyang 110001, Peoples R China. EM hongshang100@hotmail.com NR 6 TC 2 Z9 3 U1 0 U2 0 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD OCT PY 2004 VL 117 IS 10 BP 1570 EP 1572 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 866QH UT WOS:000224787500025 PM 15498386 ER PT J AU Bergmeier, W Piffath, CL Cheng, GY Dole, VS Zhang, YH von Andrian, UH Wagner, DD AF Bergmeier, W Piffath, CL Cheng, GY Dole, VS Zhang, YH von Andrian, UH Wagner, DD TI Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIb alpha shedding from platelets in vitro and in vivo SO CIRCULATION RESEARCH LA English DT Article DE platelets; TACE; GPIb alpha, shedding ID MATRIX METALLOPROTEINASES; L-SELECTIN; RECEPTOR; GLYCOCALICIN; SURFACE; DISEASE; FLOW; IX AB Interaction of the platelet receptor glycoprotein (GP) Ib-V-IX with von Willebrand factor exposed at a site of vascular injury is an essential step in the initiation of a hemostatic plug. Proteolytic cleavage (shedding) of the GPIbalpha subunit was first described >25 years ago, the protease mediating this event as well as its physiological function, however, have not been elucidated. We reported recently that shedding of GPIbalpha induced by platelet storage or mitochondrial injury involves a platelet-derived metalloproteinase(s). Here we show that GPIbalpha shedding in response to mitochondrial injury or physiological activation is inhibited in platelets obtained from chimeric mice, which express inactive tumor necrosis factor-alpha converting enzyme (TACE(DeltaZn/DeltaZn)) in blood cells only. Shedding was also inhibited in mouse and human platelets in the presence of 2 potent TACE inhibitors: TAP1 and TMI-1. Our data further suggest that TACE is important in the regulation of GPIbalpha expression in vivo because we observed an approximate to90% reduction in soluble GPIbalpha (glycocalicin) in plasma of TACE(DeltaZn/DeltaZn) chimeras as well as significantly increased levels of GPIbalpha on circulating platelets. In contrast, shedding of P-selectin from activated platelets was not affected by the mutation in TACE. Damaged TACE(DeltaZn/DeltaZn) platelets were further characterized by a markedly improved post-transfusion recovery and hemostatic function in mice. In conclusion, our data demonstrate that TACE is expressed in platelets and that it is the key enzyme mediating shedding of GPIbalpha. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Wyeth Res, Cambridge, MA USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R37 HL041002, R37 HL41002] NR 26 TC 118 Z9 125 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 1 PY 2004 VL 95 IS 7 BP 677 EP 683 DI 10.1161/01.RES.0000143899.73453.11 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 858MR UT WOS:000224196400004 PM 15345652 ER PT J AU Makarenko, I Opitz, CA Leake, MC Neagoe, C Kulke, M Gwathmey, JK del Monte, F Hajjar, RJ Linke, WA AF Makarenko, I Opitz, CA Leake, MC Neagoe, C Kulke, M Gwathmey, JK del Monte, F Hajjar, RJ Linke, WA TI Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts SO CIRCULATION RESEARCH LA English DT Article DE connectin; heart-failure; diastole/dilated-cardiomyopathy; passive-tension ID HUMAN MYOCARDIUM; MOLECULAR-BASIS; CARDIAC TITIN; CYTOSKELETON; EXPRESSION; FAILURE; MUSCLE; GIANT; PROTEIN; HYPERTROPHY AB In the pathogenesis of dilated cardiomyopathy, cytoskeletal proteins play an important role. In this study, we analyzed titin expression in left ventricles of 19 control human donors and 9 severely diseased (nonischemic) dilated cardiomyopathy (DCM) transplant-patients, using gel-electrophoresis, immunoblotting, and quantitative RT-PCR. Both human-heart groups coexpressed smaller (approximate to3 MDa) N2B-isoform and longer (3.20 to 3.35 MDa) N2BA-isoforms, but the average N2BA:N2B-protein ratio was shifted from approximate to30:70 in controls to 42: 58 in DCM hearts, due mainly to increased expression of N2BA-isoforms >3.30 MDa. Titin per unit tissue was decreased in some DCM hearts. The titin-binding protein obscurin also underwent isoform-shifting in DCM. Quantitative RT-PCR revealed a 47% reduction in total-titin mRNA levels in DCM compared with control hearts, but no differences in N2B, all-N2BA, and individual-N2BA transcripts. The reduction in total-titin transcripts followed from a decreased area occupied by myocytes and increased connective tissue in DCM hearts, as detected by histological analysis. Force measurements on isolated cardiomyofibrils showed that sarcomeric passive tension was reduced on average by 25% to 30% in DCM, a reduction readily predictable with a model of wormlike-chain titin elasticity. Passive-tension measurements on human-heart fiber bundles, before and after titin proteolysis, revealed a much-reduced relative contribution of titin to total passive stiffness in DCM. Results suggested that the titin-isoform shift in DCM depresses the proportion of titin-based stiffness by approximate to10%. We conclude that a lower-than-normal proportion of titin-based stiffness in end-stage failing hearts results partly from loss of titin and increased fibrosis, partly from titin-isoform shift. The titin-isoform shift may be beneficial for myocardial diastolic function, but could impair the contractile performance in systole. C1 Univ Munster, Physiol & Biophys Lab, D-48149 Munster, Germany. Univ Heidelberg, Inst Physiol, Heidelberg, Germany. Boston Univ, Med Ctr, Boston, MA USA. Gwathmey Inc, Boston, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. RP Linke, WA (reprint author), Univ Munster, Physiol & Biophys Lab, Schlosspl 5, D-48149 Munster, Germany. EM wlinke@uni-muenster.de RI Neagoe, Ciprian/B-5863-2011; Leake, Mark/C-1245-2011; Linke, Wolfgang/E-8662-2012; Opitz, Christiane/I-9507-2012 OI Neagoe, Ciprian/0000-0002-7328-1654; Leake, Mark/0000-0002-1715-1249; Opitz, Christiane/0000-0001-5575-9821 NR 33 TC 153 Z9 155 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 1 PY 2004 VL 95 IS 7 BP 708 EP 716 DI 10.1161/01.RES.0000143901.37063.2f PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 858MR UT WOS:000224196400008 PM 15345656 ER PT J AU Colleoni, M Viale, G Zahrieh, D Pruneri, G Gentilini, O Veronesi, P Gelber, RD Curigliano, G Torrisi, R Luini, A Intra, M Galimberti, V Renne, G Nole, F Peruzzotti, G Goldhirsch, A AF Colleoni, M Viale, G Zahrieh, D Pruneri, G Gentilini, O Veronesi, P Gelber, RD Curigliano, G Torrisi, R Luini, A Intra, M Galimberti, V Renne, G Nole, F Peruzzotti, G Goldhirsch, A TI Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: A study of preoperative treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID SURGICAL ADJUVANT BREAST; PRIMARY TUMOR REMOVAL; NEOADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; CARCINOMA; ESTROGEN; THERAPY; REGRESSION; DOCETAXEL; PATTERNS AB Purpose: The purpose of this research was to identify factors predicting response to preoperative chemotherapy. Experimental Design: In a large volume laboratory using standard immunohistochemical methods, we reviewed the pretreatment biopsies and histologic specimens at final surgery of 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) who were treated with preoperative chemotherapy. The incidence of pathological complete remission and the incidence of node-negative status at final surgery were assessed with respect to initial pathological and clinical findings. Menopausal status, estrogen receptor status, progesterone receptor status [absent (0% of the cells positive) versus expressed], clinical tumor size, histologic grade, Ki-67, Her-2/neu expression, and type and route of chemotherapy were considered. Results: High rates of pathological complete remission were associated with absence of estrogen receptor and progesterone receptor expression (P < 0.0001), and grade 3 (P = 0.001). Significant predictors of node-negative status at surgery were absence of estrogen receptor and progesterone receptor expression (P < 0.0001), clinical tumor size <5 cm (P < 0.001), and use of infusional regimens (P = 0.003). The chance of obtaining pathological complete remission or node-negative status for patients with endocrine nonresponsive tumors compared with those having some estrogen receptor or progesterone receptor expression was 4.22 (95% confidence interval, 2.20 - 8.09, 33.3% versus 7.5%) and 3.47 (95% confidence interval, 2.09-5.76, 42.9% versus 21.7%), respectively. Despite the significantly higher incidence of pathological complete remission and node-negative status achieved by preoperative chemotherapy for patients with estrogen receptor and progesterone receptor absent disease, the disease-free survival was significantly worse for this cohort compared with the low/positive expression cohort (4-year disease-free survival %: 41% versus 74%; hazard ratio 3.22; 95% confidence interval, 2.28 - 4.54; P < 0.0001). Conclusions: Response to preoperative chemotherapy is significantly higher for patients with endocrine nonresponsive tumors. New chemotherapy regimens or combinations should be explored in this cohort of patients with poor outcome. For patients with endocrine responsive disease, the role of preoperative endocrine therapies should be studied. C1 European Inst Oncol, Dept Med, Div Med Oncol, I-20141 Milan, Italy. European Inst Oncol, Dept Med, Div Senol, I-20141 Milan, Italy. European Inst Oncol, Div Pathol, Milan, Italy. Univ Milan, Sch Med, Milan, Italy. Dana Farber Canc Inst, Ctr Stat, Int Breast Canc Studt Grp, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA 02115 USA. RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it FU NCI NIH HHS [CA-75362] NR 33 TC 211 Z9 226 U1 3 U2 8 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 OCT 1 PY 2004 VL 10 IS 19 BP 6622 EP 6628 DI 10.1158/1078-0432.CCR-04-0380 PG 7 WC Oncology SC Oncology GA 862WF UT WOS:000224521300027 PM 15475452 ER PT J AU Gerson, LB Groeneveld, PW Triadafilopoulos, G AF Gerson, Lauren B. Groeneveld, Peter W. Triadafilopoulos, George TI Cost-Effectiveness Model of Endoscopic Screening and Surveillance in Patients With Gastroesophageal Reflux Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID HIGH-GRADE DYSPLASIA; QUALITY-OF-LIFE; SPECIALIZED INTESTINAL METAPLASIA; ARGON PLASMA COAGULATION; BARRETTS-ESOPHAGUS; PHOTODYNAMIC THERAPY; FOLLOW-UP; GASTRIC CARDIA; CANCER-RISK; GASTROINTESTINAL-ENDOSCOPY AB Background & Aims: Endoscopic screening and periodic surveillance for patients with Barrett's esophagus has been shown to be cost-effective in patients with esophageal dysplasia, with treatment for esophageal cancer limited to esophagectomy. Most gastroenterologists refer patients with high-grade dysplasia for esophagectomy, and effective endoscopic therapies are available for nonoperative patients with esophageal cancer. The cost-effectiveness of screening strategies that incorporate these nonsurgical treatment modalities has not been determined. Methods: We designed a Markov model to compare lifetime costs and life expectancy for a cohort of 50-year-old men with chronic reflux symptoms. We compared 10 clinical strategies incorporating combinations of screening and surveillance protocols (no screening, screening with periodic surveillance for both dysplastic and nondysplastic Barrett's esophagus, or periodic surveillance for dysplasia only), treatment for high-grade dysplasia (esophagectomy or intensive surveillance), and treatment for cancer (esophagectomy or surgical and endoscopic treatment options). Results: Screening and surveillance of patients with both dysplastic and nondysplastic Barrett's esophagus followed by esophagectomy for surgical candidates with high-grade dysplasia or esophageal cancer and endoscopic therapy for cancer patients who were not operative candidates cost $12,140 per life-year gained compared to no screening. Other screening strategies, including strategies that had no endoscopic treatment options, were either less effective at the same cost, or equally effective at a higher cost. Conclusions: The cost-effectiveness of screening and subsequent surveillance of patients with dysplastic as well as nondysplastic Barrett's esophagus followed by endoscopic or surgical therapy in patients who develop cancer compares favorably to many widely accepted screening strategies for cancer. C1 [Gerson, Lauren B.; Triadafilopoulos, George] Stanford Univ, Sch Med, Div Gastroenterol, Stanford, CA 94305 USA. [Triadafilopoulos, George] VA Palo Alto Hlth Care Syst, Gastroenterol Sect, Palo Alto, CA USA. [Groeneveld, Peter W.] Philadelphia VA Med Ctr, Sect Primary Care & Consultat Med, Philadelphia, PA USA. [Groeneveld, Peter W.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Gerson, LB (reprint author), Stanford Univ, Div Gastroenterol & Hepatol, A149, Stanford, CA 94305 USA. EM lgerson@stanford.edu FU Wellcome Institute for Digestive Health FX Dr. Gerson was supported by a Glaxo Wellcome Institute for Digestive Health Healthcare Advancement Award. NR 89 TC 58 Z9 59 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2004 VL 2 IS 10 BP 868 EP 879 DI 10.1053/S1542-3565(04)00394-5 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KV UT WOS:000208072200006 PM 15476150 ER PT J AU Sands, BE Blank, MA Patel, K Van Deventer, SJ AF Sands, Bruce E. Blank, Marion A. Patel, Kam Van Deventer, Sander J. TI Long-term Treatment of Rectovaginal Fistulas in Crohn's Disease: Response to Infliximab in the ACCENT II Study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INTRAVENOUS CYCLOSPORINE; MANAGEMENT; 6-MERCAPTOPURINE; EFFICACY AB Background & Aims: The ACCENT II study (A Crohn's Disease Clinical Trial Evaluating Infiximab in a New Long-term Treatment Regimen in Patients With Fistulizing Crohn's Disease) evaluated the efficacy and safety of infliximab maintenance treatment in patients with fistulizing Crohn's disease. This post hoc analysis was conducted to determine the efficacy and safety of infliximab therapy in women with rectovaginal fistulas. Methods: All patients received 5 mg/kg infliximab intravenously at weeks 0, 2, and 6. Patients who achieved response at weeks 10 and 14 then were randomized as responders if they had at least 50% of baseline fistulas closed, or as nonresponders, to receive placebo or infliximab 5 mg/kg every 8 weeks through week 54. Results: Of 282 patients in the ACCENT II study, 25 of 138 (18.1%) women had a total of 27 draining rectovaginal fistulas at baseline. After infusions of infliximab at weeks 0, 2, and 6, 60.7% (17 of 28) and 44.8% (13 of 29) of rectovaginal fistulas were closed at weeks 10 and 14, respectively. Among responders, 72.2% (13 of 18) of rectovaginal fistulas were no longer draining at week 14. The duration of rectovaginal fistula closure was longer in the infliximab 5-mg/kg maintenance group (median, 46 wk) than in the placebo group (33 wk). Conclusions: Infliximab is effective in short-term closure of rectovaginal fistulas and maintenance treatment was more effective than placebo in prolonging rectovaginal fistula closure. C1 [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Blank, Marion A.; Patel, Kam] Centocor Inc, Malvern, PA 19355 USA. [Van Deventer, Sander J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 7, Boston, MA 02114 USA. EM bsands@partners.org FU Centocor, Inc., Malvern, Pennsylvania; Centocor FX Supported by Centocor, Inc., Malvern, Pennsylvania. Dr. Sands has received honoraria, consulting fees, and research support from Centocor. Dr. Blank is a Centocor employee and Johnson & Johnson stockholder. Dr. van Deventer has served on the Speakers Bureau for Centocor. NR 20 TC 141 Z9 148 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2004 VL 2 IS 10 BP 912 EP 920 DI 10.1053/S1542-3565(04)00414-8 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KV UT WOS:000208072200011 PM 15476155 ER PT J AU Lipsky, BA Berendt, AR Deery, HG Embil, JM Joseph, WS Karchmer, AW LeFrock, JL Lew, DP Mader, JT Norden, C Tan, JS AF Lipsky, BA Berendt, AR Deery, HG Embil, JM Joseph, WS Karchmer, AW LeFrock, JL Lew, DP Mader, JT Norden, C Tan, JS TI Diagnosis and treatment of diabetic foot infections SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID COLONY-STIMULATING FACTOR; SOFT-TISSUE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; PERIPHERAL VASCULAR-DISEASE; ARTERIAL OCCLUSIVE DISEASE; LOWER-EXTREMITY INFECTIONS; CUTANEOUS OXYGEN-TENSION; TOE BLOOD-PRESSURE; OPEN-LABEL TRIAL; TERM-FOLLOW-UP C1 Univ Washington, Sch Med, Med Serv, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gen Med, Seattle, WA 98108 USA. Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford OX3 7LD, England. No Michigan Infect Dis, Petoskey, MI USA. Univ Manitoba, Dept Med, Infect Dis Sect, Winnipeg, MB, Canada. Vet Affairs Med Ctr, Dept Primary Care, Sect Podiatry, Coatesville, PA USA. Harvard Univ, Sch Med, Div Infect Dis, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dimens Dosing Syst, Sarasota, FL USA. Univ Geneva Hosp, Dept Med, Infect Dis Serv, Geneva, Switzerland. Univ Texas, Med Branch, Dept Internal Med, Inst Marine Biomed, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Orthopaed & Rehabil, Galveston, TX 77550 USA. New Jersey Sch Dent & Med, Dept Med, Camden, NJ USA. Cooper Hosp Univ Med Ctr, Camden, NJ USA. Summa Hlth Syst, Dept Internal Med, Akron, OH USA. NE Ohio Univ, Coll Med, Akron, OH USA. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, Med Serv, Vet Affairs Puget Sound Hlth Care Syst, S-111-GIMC,1600 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.Lipsky@med.va.gov RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 297 TC 445 Z9 469 U1 5 U2 40 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 OCT 1 PY 2004 VL 39 IS 7 BP 885 EP 910 DI 10.1086/424846 PG 26 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JE UT WOS:000227491600001 PM 15472838 ER PT J AU Rodriguez, M Fishman, JA AF Rodriguez, M Fishman, JA TI Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID BONE-MARROW-TRANSPLANTATION; CARINII-PNEUMONIA PROPHYLAXIS; DIHYDROPTEROATE SYNTHASE GENE; TRIMETHOPRIM-SULFAMETHOXAZOLE-INTOLERANT; DOSE COTRIMOXAZOLE PROPHYLAXIS; RECEIVING DAPSONE PROPHYLAXIS; PRIMARY BRAIN-TUMORS; 10 YEARS EXPERIENCE; IN-VITRO ACTIVITY; AEROSOLIZED PENTAMIDINE AB Pneumocystis infection in humans was originally described in 1942 The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving immunosuppressive therapies for connective tissue disorders and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for prophylaxis against Pneumocystis unless a clear contraindication is identified. Other options include pentamidine, dapsone, dapsone-pyrimethamine, and atovaquone. The risk for PCP varies based on individual immune defects, regional differences, and immunosuppressive regimens. Prophylactic strategies must be linked to an ongoing assessment of the patient's risk for disease. C1 Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 177 TC 110 Z9 115 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2004 VL 17 IS 4 BP 770 EP + DI 10.1128/CMR.17.4.770-782.2004 PG 14 WC Microbiology SC Microbiology GA 864ZE UT WOS:000224671100004 PM 15489347 ER PT J AU Vucic, S Dawson, K Sun, D Cros, D AF Vucic, S Dawson, K Sun, D Cros, D TI Pure motor mononeuropathy with distal conduction block: an unusual presentation of multifocal motor neuropathy with conduction blocks SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE multifocal motor neuropathy with conduction block; spinal accessory nerve; intravenous immunoglobulin; distal conduction block ID GUILLAIN-BARRE-SYNDROME; ROOT STIMULATION; DEMYELINATING NEUROPATHY; NEURON DISEASE; DIAGNOSIS; CRITERIA; MUSCLE; UNITS AB Objective: To report an hitherto undescribed presentation of Motor Neuropathy with Multifocal Conduction Block (MMNCB). Methods: Description of two patients presenting with complete paralysis of the 3 heads of the trapezius muscle (case one) and progressive weakness of finger extension (case 2). Results: Nerve conduction studies (NCS) established that the corresponding nerves were distally inexcitable. In the affected muscles, no voluntary activity was elicited in both patients with spontaneous activity noted in patient 2. Systematic NCSs documented an asymptomatic, partial conduction block (CB) in a median nerve forearm segment in both patients. Neurophysiological follow-up after a dramatic response to intravenous immunoglobulins demonstrated recovery of the initially unobtainable motor responses. Conclusions: This indicates that a complete, distal CB of the motor fibers destined to the trapezius muscle in patient 1, and to the extensor indicis proprius in patient 2, had caused the heralding deficits. Significance: These findings underscore the possibility of distal CB in this disorder and the need for extensive NCSs, including asymptomatic nerves, for an accurate diagnosis. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. EM dcros@partners.org NR 26 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2004 VL 115 IS 10 BP 2323 EP 2328 DI 10.1016/j.clinph.2004.05.003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 856KV UT WOS:000224045000014 PM 15351374 ER PT J AU Vucic, S Cairns, KD Black, KR Chong, PST Cros, D AF Vucic, S Cairns, KD Black, KR Chong, PST Cros, D TI Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE acute inflammatory demyelinating polyradiculoneuropathy; Guillain-Barre syndrome; neurophysiology ID GUILLAIN-BARRE-SYNDROME; CONDUCTION BLOCK; ELECTRODIAGNOSTIC ABNORMALITIES; NERVE-CONDUCTION; PLASMA-EXCHANGE; A-WAVES; POLYNEUROPATHY; CRITERIA; FEATURES AB Background: Patients with early acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may not meet the current neurophysiologic criteria. Objective: To document neurophysiologic findings in early AIDP. Methods: Clinical and neurophysiologic data from 38 AIDP patients, assessed within 10 days of symptom onset were reviewed. Results: In addition to absent H reflexes and abnormal F-wave responses in the acute stage of AIDP, abnormalities of blink reflexes, upper limb sensory responses abnormalities with spared sural responses, presence of distal CMAP dispersion, and A-waves were frequently observed. Established demyelinating neurophysiologic parameters were infrequently seen. Conclusions: Abnormalities of H reflexes and F responses were most frequently noted in early AIDP. Additionally, distal temporal dispersion, prolonged or absent blink reflexes, and A-waves were often present in the acute stage of AIDP when classic diagnostic criteria of AIDP were not satisfied. Significance: Neurophysiologic studies in early AIDP frequently reveal abnormalities that are not specific of primary demyelinating neuropathy. (C) 2004 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM dcros@partners.org NR 29 TC 40 Z9 46 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2004 VL 115 IS 10 BP 2329 EP 2335 DI 10.1016/j.clinph.2004.05.009 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 856KV UT WOS:000224045000015 PM 15351375 ER PT J AU Gray, ML Eckstein, F Peterfy, C Dahlberg, L Kim, YJ Sorensen, AG AF Gray, ML Eckstein, F Peterfy, C Dahlberg, L Kim, YJ Sorensen, AG TI Toward imaging biomarkers for osteoarthritis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Carl T Brighton Annual Workshop CY NOV 14, 2004 CL Tampa Bay, FL ID KNEE CARTILAGE VOLUME; SPIN-ECHO MR; EARLY RHEUMATOID-ARTHRITIS; GADOLINIUM-ENHANCED MRI; FIXED CHARGE-DENSITY; ARTICULAR-CARTILAGE; MAGNETIC-RESONANCE; IN-VIVO; GD-DTPA; QUANTITATIVE ASSESSMENT AB Many new therapeutic strategies have been and are being developed to correct, prevent, or slow the progression of osteoarthritis. Our ability to evaluate the efficacy of these techniques, or to determine the situations for which they might provide the most benefit, critically depends on diagnostic measures that can serve as proxies for the present or predicted state of the cartilage. Many of the magnetic resonance imaging techniques that have been emerging over the past decades appear promising in that they have shown technical validity in measuring the morphologic and molecular state of cartilage. With continued development and added insight from pilot clinical studies, these or related methods may soon be in customary use. These techniques are part of a paradigm shift where therapeutic strategies are developed hand-in-hand with diagnostic approaches-a shift that offers the promise of speeding development of effective therapies, and focusing their use in areas where they can be most successful. C1 Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. New England Baptist Bone & Joint Inst, Boston, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Univ Munich, Inst Anat, Munich, Germany. Synarc Corp, San Francisco, CA USA. Univ Hosp, Dept Orthoped, Malmo, Sweden. Childrens Hosp, Dept Orthoped, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gray, ML (reprint author), MIT Room E25-519, Cambridge, MA 02139 USA. EM mgray@mit.edu RI Eckstein, Felix/E-1585-2011 NR 74 TC 46 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2004 IS 427 SU S BP S175 EP S181 DI 10.1097/01.blo.0000144972.50849.d9 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 862XI UT WOS:000224524400029 PM 15480063 ER PT J AU Hamner, MB Robert, S Frueh, BC AF Hamner, MB Robert, S Frueh, BC TI Treatment-resistant posttraumatic stress disorder: Strategies for intervention SO CNS SPECTRUMS LA English DT Review ID TREATMENT-REFRACTORY DEPRESSION; PLACEBO-CONTROLLED STUDY/; COMBAT-RELATED PTSD; DOUBLE-BLIND; OPEN-LABEL; SERTRALINE TREATMENT; CONTROLLED-TRIAL; COMPENSATION-SEEKING; ADJUNCTIVE THERAPY; PSYCHOTIC FEATURES AB The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex Psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. TO date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment refractory PTSD. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, PTSD Clin Treatment Team, Charleston, SC 29401 USA. Ralph H Johnson VA Med Ctr, Psychiat Res Sect, Charleston, SC 29401 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM hamnermb@musc.edu NR 124 TC 45 Z9 47 U1 3 U2 7 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 OCT PY 2004 VL 9 IS 10 BP 740 EP 752 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VL UT WOS:000226891800010 PM 15448585 ER PT J AU Rice, CA AF Rice, CA TI Introduction to group therapy SO CONTEMPORARY PSYCHOLOGY-APA REVIEW OF BOOKS LA English DT Book Review C1 Widener Univ, Inst Grad Clin Psychol, Chester, PA 19013 USA. RP Rice, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 23 Briarwood Circle, Needham, MA 02494 USA. EM cecilrise@attbi.com NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD OCT PY 2004 VL 49 IS 5 BP 553 EP 555 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 863LW UT WOS:000224564300016 ER PT J AU Andreoli, CM Wiley, HE Durand, ML Watkins, LM AF Andreoli, CM Wiley, HE Durand, ML Watkins, LM TI Primary meningococcal conjunctivitis in an adult SO CORNEA LA English DT Article DE conjunctivitis; Neisseria meningitidis; meningitis AB Purpose: To describe a case of primary meningococcal conjunctivitis mimicking epidemic keratoconjunctivitis. Methods: Review of a case history and current literature. Results: A 28-year-old man presented with 5 days of a bilateral follicular conjunctivitis and subepithelial corneal infiltrates. Initial diagnosis of adenoviral conjunctivitis was made. Initial Gram stain of conjunctival exudates was negative. Cultures grew Neisseria meningitidis. Systemic antibiotics were instituted with adjunctive topical therapy. The conjunctivitis resolved with no evidence of systemic invasion. Conclusions: The clinical picture of Neisseria meningitidis conjunctivitis can overlap with other infectious organisms including adenovirus. Early diagnosis and systemic antibiotic therapy are critical to prevent bacteremic spread of infection. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Emergency Ophthalmol Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Infect Dis, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. RP Andreoli, CM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM christopher_andreoli@hms.harvard.edu NR 5 TC 5 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD OCT PY 2004 VL 23 IS 7 BP 738 EP 739 DI 10.1097/01.ico.0000126316.82648.56 PG 2 WC Ophthalmology SC Ophthalmology GA 859DA UT WOS:000224241300020 PM 15448506 ER PT J AU Taccone, P Hess, D Caironi, P Bigatello, LM AF Taccone, P Hess, D Caironi, P Bigatello, LM TI Continuous positive airway pressure delivered with a "helmet": Effects on carbon dioxide rebreathing SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 99th International Conference of the American-Thoracic-Society CY MAY 16-23, 2003 CL SEATTLE, WA SP Amer Thorac Soc DE noninvasive ventilation; carbon dioxide rebreathing; helmet; face mask; acute respiratory failure; continuous positive airway pressure ID HYPOXEMIC RESPIRATORY-FAILURE; FACE MASK; VENTILATION AB Objective. The "helmet" has been used as a novel interface to deliver noninvasive ventilation without applying direct pressure on the face. However, due to its large volume, the helmet may predispose to Co-2 rebreathing. We hypothesized that breathing with the helmet is similar to breathing in a semiclosed environment, and therefore the Pco(2) inside the helmet is primarily a function of the subject's Co-2 production and the flow of fresh gas through the helmet. Design: Human volunteer study. Setting: Laboratory in a university teaching hospital. Subjects: Eight healthy volunteers. Interventions: We delivered continuous positive airway pressure (CPAP) with the helmet under a variety of ventilatory conditions in a lung model and in volunteers. Measurements and Main Results: Gas flow and Co-2 concentration at the airway were measured continuously. End-tidal Pco(2), Co-2 production, and ventilatory variables were subsequently computed. We found that a) When CPAP was delivered with a ventilator, the inspired Co-2 of the volunteers was high (12.4 +/- 3.2 torr [1.7 +/- 0.4 kPa]); b) when CPAP was delivered with a continuous high flow system, inspired Co-2 of the volunteers was low (2.5 +/- 1.2 torr [0.3 +/- 0.2 kPa]); and c) the inspired Co-2 calculated mathematically for a semiclosed system model of Co-2 rebreathing was highly correlated with the values measured in a lung model (r(2) = .97, slope = 0.92, intercept = -1.17, p < .001) and in the volunteers (r(2) = .94, slope = 0.96, intercept = 0.90, p < .001). Conclusions: a) The helmet predisposes to Co-2 rebreathing and should not be used to deliver CPAP with a ventilator; b) continuous high flow minimizes Co-2 rebreathing during CPAP with the helmet; and c) minute ventilation and Pco(2) should be monitored during CPAP with the helmet. C1 Univ Milan, Osped Maggiore Milano, IRCCS, Ist Anestensi & Rianimaz, Milan, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02115 USA. RP Taccone, P (reprint author), Univ Milan, Osped Maggiore Milano, IRCCS, Ist Anestensi & Rianimaz, Milan, Italy. NR 14 TC 75 Z9 77 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2004 VL 32 IS 10 BP 2090 EP 2096 DI 10.1097/01.CCM.0000142577.63316.C0 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 865HH UT WOS:000224692800016 PM 15483419 ER PT J AU Majeski, EI Widener, CE Basile, J AF Majeski, EI Widener, CE Basile, J TI Hypertension and dementia: Does blood pressure control favorably affect cognition? SO CURRENT HYPERTENSION REPORTS LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; HEALTH INITIATIVE MEMORY; ELDERLY PROGRAM SHEP; ALZHEIMER-DISEASE; POSTMENOPAUSAL WOMEN; VASCULAR DEMENTIA; CONTROLLED-TRIAL; DIETARY-INTAKE; RISK; IMPAIRMENT AB Dementia and aging are not synonymous. Dementia is a progressive deterioration in cognitive and social and/or occupational functions that can eventually impair a patients ability to live independently. Alzheimer's disease is the most common form of dementia. Vascular dementis, responsible for up to 15% of all diagnosed cases, is the second most common form of dementia. Hypertension remains a significant risk factor for vascular dementia. The optimal level of blood pressure control for the prevention of dementia and whether one particular class of antihypertensive drug is more beneficial than another remains uncertain. C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Majeski, EI (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM Jan.Basile@med.va.gov NR 30 TC 5 Z9 5 U1 3 U2 5 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD OCT PY 2004 VL 6 IS 5 BP 357 EP 362 DI 10.1007/s11906-004-0054-0 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 991HJ UT WOS:000233802800006 PM 15341687 ER PT J AU Alper, CA Larsen, CE AF Alper, CA Larsen, CE TI Immunogenetics - Human immunogenetics - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Alper, CA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM alper@cbr.med.harvard.edu; larsen@cbr.med.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2004 VL 16 IS 5 BP 623 EP 625 DI 10.1016/j.coi.2004.08.003 PG 3 WC Immunology SC Immunology GA 854NS UT WOS:000223911200015 ER PT J AU Larsen, CE Alper, CA AF Larsen, CE Alper, CA TI The genetics of HLA-associated disease SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID DEPENDENT DIABETES-MELLITUS; MAJOR HISTOCOMPATIBILITY COMPLEX; CONSERVED EXTENDED HAPLOTYPE; SUSCEPTIBILITY GENES; IDENTICAL-TWINS; CELIAC-DISEASE; IGA DEFICIENCY; POPULATION; MHC; ALLELE AB Type 1 diabetes mellitus (T1D) remains the most intensively studied, and thus the best paradigm, of MHC-associated diseases. Accumulating evidence suggests that MHC susceptibility for T1D is recessive, with susceptibility alleles more common than protective alleles. Updated allele-level and nucleotide sequence analysis of MHC class II T1D susceptibility markers of conserved extended haplotypes underscore the uncertainty surrounding the actual T1D MHC susceptibility locus. Recent studies have established that disease concordance in dizygotic twins is the same as that in siblings generally, for both T1D and the MHC-associated autoimmune disease gluten-sensitive enteropathy, leaving little room for a differential environmental trigger. Epigenetic mechanisms are probably involved in many MHC-associated phenomena, including autoimmunity, and appear to be the best explanation for incomplete penetrance. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Larsen, CE (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM alper@cbr.med.harvard.edu FU NHLBI NIH HHS [HL-29583] NR 54 TC 62 Z9 65 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2004 VL 16 IS 5 BP 660 EP 667 DI 10.1016/j.coi.2004.07.014 PG 8 WC Immunology SC Immunology GA 854NS UT WOS:000223911200020 PM 15342014 ER PT J AU Sheen, J Kay, S AF Sheen, J Kay, S TI Cell signalling and gene regulation - Exploring new functions and actions of regulatory molecules - Editorial overview SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Scripps Res Inst, La Jolla, CA 92037 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 11, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu; stevek@scripps.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD OCT PY 2004 VL 7 IS 5 BP 487 EP 490 DI 10.1016/j.pbi.2004.07.017 PG 4 WC Plant Sciences SC Plant Sciences GA 856AK UT WOS:000224015800001 ER PT J AU Oakes, SA Korsmeyer, SJ AF Oakes, SA Korsmeyer, SJ TI Untangling the web: Mitochondrial fission and apoptosis SO DEVELOPMENTAL CELL LA English DT Editorial Material ID HFIS1 AB Mitochondria exist as an interconnected network that is constantly remodeled by balancing membrane fission and fusion events. A new study by Szabadkai et al. in the October 8(th) issue of Molecular Cell shows that dynamin-related protein 1 (Drp1)-induced scission hinders the ability of mitochondria to transport calcium across the cell and mediate apoptosis. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst,Dept Pathol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst,Dept Med, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Oakes, SA (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst,Dept Pathol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. NR 9 TC 9 Z9 10 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2004 VL 7 IS 4 BP 460 EP 462 DI 10.1016/j.devcel.2004.09.010 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 864ZG UT WOS:000224671300003 PM 15469833 ER PT J AU Krause, M Leslie, JD Stewart, M Lafuente, EM Valderrama, F Jagannathan, R Strasser, GA Rubinson, DA Liu, H Way, M Yaffe, MB Boussiotis, VA Gertier, FB AF Krause, M Leslie, JD Stewart, M Lafuente, EM Valderrama, F Jagannathan, R Strasser, GA Rubinson, DA Liu, H Way, M Yaffe, MB Boussiotis, VA Gertier, FB TI Lamellipodin, an EnaNASP ligand, is implicated in the regulation of lamellipodial dynamics SO DEVELOPMENTAL CELL LA English DT Article ID ACTIN-BASED MOTILITY; ENA/VASP PROTEINS; ARP2/3 COMPLEX; PHOSPHOINOSITIDE-BINDING; CHEMOATTRACTANT RECEPTOR; LISTERIA-MONOCYTOGENES; CYTOSKELETAL PROTEINS; FIBROBLAST MOTILITY; HOMOLOGY DOMAINS; MAMMALIAN-CELLS AB Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility. Lpd contains a PH domain that binds specifically to PI(3,4)P-2, an asymmetrically localized signal in chemotactic cells. Lpd's PH domain can localize to ruffles in PDGF-treated fibroblasts. Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane. Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content. These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Res UK, Cell Motil Grp, Lincolns Inn Fields Labs, London WC2A 3PX, England. RP Gertier, FB (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA. EM fgertler@mit.edu RI Valderrama, Ferran/E-8017-2011; Lafuente, Esther M/K-5684-2014; Krause, Matthias/D-9814-2013 OI Lafuente, Esther M/0000-0001-8466-1022; Krause, Matthias/0000-0002-3200-3199 FU NIGMS NIH HHS [GM68678] NR 50 TC 169 Z9 176 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2004 VL 7 IS 4 BP 571 EP 583 DI 10.1016/j.devcel.2004.07.024 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 864ZG UT WOS:000224671300015 PM 15469845 ER PT J AU Lafuente, EM van Puijenbroek, AAFL Krause, M Carman, CV Freeman, GJ Berezovskaya, A Constantine, E Springer, TA Gertier, FB Boussiotis, VA AF Lafuente, EM van Puijenbroek, AAFL Krause, M Carman, CV Freeman, GJ Berezovskaya, A Constantine, E Springer, TA Gertier, FB Boussiotis, VA TI RIAM, an EnaNASP and profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion SO DEVELOPMENTAL CELL LA English DT Article ID SMALL GTPASE RAP1; T-CELL; ACTIN CYTOSKELETON; ENA/VASP PROTEINS; LISTERIA-MONOCYTOGENES; INTEGRIN ACTIVATION; SUPPRESSOR ACTIVITY; MOTILITY; FAMILY; VASP AB The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics. Overexpression of RIAM induced cell spreading and lamellipodia formation, changes that require actin polymerization. In contrast, RIAM knockdown cells had reduced content of polymerized actin. RIAM overexpression also induced integrin activation and cell adhesion. RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu RI Lafuente, Esther M/K-5684-2014; Carman, Christopher/L-8108-2016; Krause, Matthias/D-9814-2013 OI Lafuente, Esther M/0000-0001-8466-1022; Carman, Christopher/0000-0001-7358-2548; Krause, Matthias/0000-0002-3200-3199 FU NIAID NIH HHS [AI 43552, AI 41584, AI 46584]; NIGMS NIH HHS [GM68676] NR 43 TC 243 Z9 259 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2004 VL 7 IS 4 BP 585 EP 595 DI 10.1016/j.devcel.2004.07.021 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 864ZG UT WOS:000224671300016 PM 15469846 ER PT J AU Levin, BE Routh, VH Kang, L Sanders, NM Dunn-Meynell, AA AF Levin, BE Routh, VH Kang, L Sanders, NM Dunn-Meynell, AA TI Perspectives in diabetes - Neuronal glucosensing what do we know after 50 years? SO DIABETES LA English DT Article ID SENSITIVE K+ CHANNELS; FOS-LIKE IMMUNOREACTIVITY; PANCREATIC BETA-CELLS; OBESE ZUCKER RATS; LOWER BRAIN-STEM; HYPOTHALAMIC NEURONS; FOOD-INTAKE; EXTRACELLULAR GLUCOSE; ARCUATE NUCLEUS; POTASSIUM CHANNELS AB Glucosensing neurons are specialized cells that use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Glucokinase (GK) appears to be the primary regulator of most neuronal glucosensing, but other regulators almost certainly exist. Glucose-excited neurons increase their activity when glucose levels rise, and most use GK and an ATP-sensitive K+ channel as the ultimate effector of glucose-induced signaling. Glucose-inhibited (GI) neurons increase their activity at low glucose levels. Although many use GK, it is unclear what the final pathway of GI neuronal glucosensing is. Glucosensing neurons are located in brain sites and respond to and integrate a variety of hormonal, metabolic, transmitter, and peptide signals involved in the regulation of energy homeostasis and other biological functions. Although it is still uncertain whether daily fluctuations in blood glucose play a specific regulatory role in these physiological functions, it is clear that large decreases in glucose availability stimulate food intake and counterregulatory responses that restore glucose levels to sustain cerebral function. Finally, glucosensing is altered in obesity and after recurrent bouts of hypoglycemia, and this altered sensing may contribute to the adverse outcomes of these conditions. Thus, although much is known, much remains to be learned about the physiological function of brain glucosensing neurons. C1 NJ Hlth Care Syst, Neurol Serv 127C, Dept Vet Affairs, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, Sch Med, Dept Neurol & Neurosci, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Sch Med, Dept Pharmacol & Physiol, Newark, NJ 07103 USA. VA Puget Sound Hlth Care Syst, Metab Endocrinol Serv, Seattle, WA USA. RP Levin, BE (reprint author), NJ Hlth Care Syst, Neurol Serv 127C, Dept Vet Affairs, 385 Tremont Ave, E Orange, NJ 07018 USA. EM levin@umdnj.edu NR 96 TC 262 Z9 267 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2004 VL 53 IS 10 BP 2521 EP 2528 DI 10.2337/diabetes.53.10.2521 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KU UT WOS:000224116100001 PM 15448079 ER PT J AU Qin, XB Goldfine, A Krumrei, N Grubissich, L Acosta, J Chorev, M Hays, AP Halperin, JA AF Qin, XB Goldfine, A Krumrei, N Grubissich, L Acosta, J Chorev, M Hays, AP Halperin, JA TI Glycation inactivation of the complement regulatory protein CD59 - A possible role in the pathogenesis of the vascular complications of human diabetes SO DIABETES LA English DT Article ID MEMBRANE ATTACK COMPLEX; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; FIBROBLAST-GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; KAPPA-B; ACTIVATION; C5B-9; MELLITUS; SURFACE AB Micro- and macrovascular diseases are major causes of morbidity and mortality in the diabetic population, but the cellular and molecular mechanisms that link hyperglycemia to these complications remain incompletely understood. We proposed that in human diabetes, inhibition by glycation of the complement regulatory protein CD59 increases deposition of the membrane attack complex (MAC) of complement, contributing to the higher vascular risk. We report here 1) the generation and characterization of an anti-glycated human CD59 (hCD59) specific antibody, 2) the detection with this antibody of glycated hCD59 colocalized with MAC in kidneys and nerves from diabetic but not from nondiabetic subjects, and 3) a significantly reduced activity of hCD59 in erythrocytes from diabetic subjects, a finding consistent with glycation inactivation of hCD59 in vivo. Because hCD59 acts as a specific inhibitor of MAC formation, these findings provide a molecular explanation for the increased MAC deposition reportedly found in the target organs of diabetic complications. We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes. C1 Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA USA. Joslin Diabet Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Columbia Univ, New York, NY USA. RP Halperin, JA (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM jose_halperin@hms.harvard.edu FU NCRR NIH HHS [M01 RR01032]; NIDDK NIH HHS [R01 DK52855, R01 DK62294] NR 50 TC 57 Z9 71 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 OCT PY 2004 VL 53 IS 10 BP 2653 EP 2661 DI 10.2337/diabetes.53.10.2653 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KU UT WOS:000224116100019 PM 15448097 ER PT J AU Grant, RW Cagliero, E Sullivan, CM Dubey, AK Estey, GA Weil, EM Gesmundo, J Nathan, DM Singer, DE Chueh, HC Meigs, JB AF Grant, RW Cagliero, E Sullivan, CM Dubey, AK Estey, GA Weil, EM Gesmundo, J Nathan, DM Singer, DE Chueh, HC Meigs, JB TI A controlled trial of population management - Diabetes mellitus: Putting evidence into practice (DM-PEP) SO DIABETES CARE LA English DT Article ID PRIMARY-CARE; GLYCEMIC CONTROL; CHRONIC ILLNESS; RISK-FACTORS; DISEASE; PATIENT; HEALTH; ADULTS; US; HYPERTENSION AB OBJECTIVE - Population-level strategies to organize and deliver care may improve diabetes management. We conducted a multiclinic controlled trial of population management in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - We created diabetic patient registries (n = 3,079) for four primary care clinics within a single academic health center. In the intervention clinic (n = 898) a nurse practitioner used novel clinical software (PopMan) to identify patients on a weekly basis with outlying values for visit and testing intervals and last measured levels of HbA(1c), LDL cholesterol, an blood pressure. For these patients, the nurse practitioner e-mailed a concise patient-specific summary of evidence-based management suggestions directly to primary care providers (PCPs). Population changes in risk factor testing, medication prescription, and risk factor levels from baseline (1 January 2000 to 31 August 2001) to follow-up (1 December 2001 to 31 July 2003) were compared with the three usual-care control clinics (n = 2,181). RESULTS - Patients had a mean age of 65 years, were mostly white (81%), and the majority were insured by Medicare/Medicaid (62%). From baseline to follow-up, the increase in proportion of patients tested for HbA(1c) (P = 0.004) and LDL cholesterol (P < 0.001) was greater in the intervention than control sites. improvements in diabetes-related medication prescription and levels of HbA(1c), LDL cholesterol, and blood pressure in the intervention clinic were balanced by similar improvements in the control sites. CONCLUSIONS - Population-level clinical registries combined with summarized recommendations to PCPs had a modest effect on management. The intervention was limited by good overall quality of care at baseline and temporal improvements in all control clinics. It is unknown whether this intervention would have had greater impact in clinical settings with lower overall quality. Further research into more effective Methods of translating population registry information into action is required. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Revere Hlth Care Ctr, Revere, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 NR 36 TC 37 Z9 37 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2299 EP 2305 DI 10.2337/diacare.27.10.2299 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700002 PM 15451891 ER PT J AU Hollander, PA Blonde, L Rowe, R Mehta, AE Milburn, JL Hershon, KS Chiasson, JL Levin, SR AF Hollander, PA Blonde, L Rowe, R Mehta, AE Milburn, JL Hershon, KS Chiasson, JL Levin, SR CA Exubera Phase III Study Grp TI Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes - Results of a 6-month, randomized, comparative trial SO DIABETES CARE LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2001 CL PHILADELPHIA, PA SP Amer Diabetes Assoc ID MICROVASCULAR COMPLICATIONS; BLOOD-GLUCOSE; MELLITUS; PROGRESSION; GLYCEMIA; NIDDM; RISK AB OBJECTIVE- Glycerine control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections. RESEARCH DESIGN AND METHODS - Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA(1C) from baseline to the end of study. RESULTS- HbA(1c) decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI-0.32 to 0.17). HbA(1c), <7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group. CONCLUSION- inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen. C1 Baylor Univ, Med Ctr, Endocrinol Ctr, Dallas, TX 75246 USA. Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. Dalhousie Univ, Dept Med, Div Endocrinol, Halifax, NS, Canada. Cleveland Clin Fdn, Cleveland, OH 44195 USA. N Texas Hlth Care Associates, Irving, TX USA. N Shore Diabet & Endocrine Associates, New Hyde Pk, NY USA. Univ Montreal, Res Ctr, Dept Med, Ctr Hosp, Montreal, PQ, Canada. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Hollander, PA (reprint author), Baylor Univ, Med Ctr, Endocrinol Ctr, 3600 Gaston Ave,Wadley Tower, Dallas, TX 75246 USA. NR 28 TC 152 Z9 157 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2356 EP 2362 DI 10.2337/diacare.27.10.2356 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700011 PM 15451900 ER PT J AU Shetty, GK Economides, PA Horton, ES Mantzoros, CS Veves, A AF Shetty, GK Economides, PA Horton, ES Mantzoros, CS Veves, A TI Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes SO DIABETES CARE LA English DT Article ID DENSITY-LIPOPROTEIN-CHOLESTEROL; NITRIC-OXIDE SYNTHASE; INSULIN-RESISTANCE; REDUCTASE INHIBITORS; PLASMA ADIPONECTIN; ADIPOSE-TISSUE; ENDOTHELIAL FUNCTION; PROTEIN ADIPONECTIN; OBESITY; ATORVASTATIN AB OBJECTIVE - Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study, to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels. RESEARCH DESIGN AND METHODS - Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-con trolled study. RESULTS - In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered. CONCLUSIONS - We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin's associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, 99 Brookline Ave,RN 325A, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu FU NCRR NIH HHS [RR-01032]; NIDDK NIH HHS [F32-DK-64550-01A1]; PHS HHS [R0-158785] NR 48 TC 281 Z9 292 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2450 EP 2457 DI 10.2337/diacare.27.10.2450 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700026 PM 15451915 ER PT J AU Rana, JS Mittleman, MA Sheikh, J Hu, FB Manson, JE Colditz, GA Speizer, FE Barr, RG Camargo, CA AF Rana, JS Mittleman, MA Sheikh, J Hu, FB Manson, JE Colditz, GA Speizer, FE Barr, RG Camargo, CA TI Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women SO DIABETES CARE LA English DT Article ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; OXIDATIVE STRESS; GENE-TRANSCRIPTION; LUNG-FUNCTION; TNF-ALPHA; MELLITUS; WEIGHT; COHORT AB OBJECTIVE - Inflammation plays a key role in chronic obstructive pulmonary disease (COPD) and asthma. Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD and asthma with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - The Nurses' Health Study is a prospective cohort study. From 1988-1996, 103,614 female nurses were asked biennially about a physician diagnosis of emphysema, chronic bronchitis, asthma, and diabetes. RESULTS - During 8 years of follow-up, we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2 diabetes was significantly higher for patients with COPD than those without (multivariate relative risk 1.8, 95% CI 1.1-2.8). By contrast, the risk of type 2 diabetes among asthmatic patients was not increased (1.0, 0.8-1.2). The asthma results remained non-significant even when we evaluated diabetes risk by duration of asthma exposure. CONCLUSIONS - Our findings suggest that COPD may be a risk factor for developing type 2 diabetes. Differences in the inflammation and cytokine profile between COPD and asthma might explain why COPD, but not asthma, is associated with increased risk of type 2 diabetes. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Allergy & Inflammat, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Dept Med,Med Sch, Boston, MA USA. Columbia Presbyterian Med Ctr, Dept Med, Div Gen Med, New York, NY USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM ccamargo@partners.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R01 CA87969]; NHLBI NIH HHS [R01 HL63841, T32 HL07374, T32 HL07427]; NIDDK NIH HHS [R01 DK58845] NR 47 TC 121 Z9 132 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2478 EP 2484 DI 10.2337/diacare.27.10.2478 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700030 PM 15451919 ER PT J AU Egede, LE Poston, ME AF Egede, LE Poston, ME TI Racial/ethnic differences in leisure-time physical activity levels among individuals with diabetes SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ADULTS C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, 135 Cannon St,Suite 403,POB 250837, Charleston, SC 29425 USA. EM egedel@musc.edu FU AHRQ HHS [5K08HS11418] NR 11 TC 15 Z9 15 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2493 EP 2494 DI 10.2337/diacare.27.10.2493 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700034 PM 15451923 ER PT J AU Fong, DS Aiello, LP Ferris, FL Klein, R AF Fong, DS Aiello, LP Ferris, FL Klein, R TI Diabetic retinopathy SO DIABETES CARE LA English DT Review ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; BLOOD-PRESSURE CONTROL; OPTICAL COHERENCE TOMOGRAPHY; POSTERIOR HYALOIDAL TRACTION; EPITHELIUM-DERIVED FACTOR; DIFFUSE MACULAR EDEMA; VITAMIN-E; MICROVASCULAR COMPLICATIONS; INTRAVITREAL TRIAMCINOLONE C1 So Calif Permanente Med Grp, Dept Res & Evaluat, Pasadena, CA 91101 USA. So Calif Permanente Med Grp, Dept Ophthalmol, Baldwin Pk, CA USA. So Calif Permanente Med Grp, Dept Res & Evaluat, Pasadena, CA USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. NEI, Dept Clin Res, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. RP Fong, DS (reprint author), So Calif Permanente Med Grp, Dept Res & Evaluat, 100 S Los Robles, Pasadena, CA 91101 USA. NR 131 TC 268 Z9 280 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2004 VL 27 IS 10 BP 2540 EP 2553 DI 10.2337/diacare.27.10.2540 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857KQ UT WOS:000224115700045 PM 15451934 ER PT J AU Lieber, CS AF Lieber, CS TI The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role SO DRUG METABOLISM REVIEWS LA English DT Review DE microsomal ethanol oxidizing system; CYP2E1; alcohol dehydrogenase; nonalcoholic steatohepatitis; nonalcoholic fatty liver disease ID FRAGMENT-LENGTH-POLYMORPHISM; BLOOD-ALCOHOL CONCENTRATIONS; RAT-LIVER MICROSOMES; HUMAN CYP2E1 GENE; CYTOCHROME-P450 2E1; LUNG-CANCER; NONALCOHOLIC STEATOHEPATITIS; ACETONE METABOLISM; HEPATIC MICROSOMES; FATTY LIVER AB Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance. This fact, as well as the discovery of the proliferation of the smooth endoplasmic reticulum (SER) after chronic alcohol consumption, suggested the existence of an additional pathway which was then described by Lieber and DeCarli, namely the microsomal ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this system was initially challenged but the effect of ethanol on liver microsomes was confirmed by Remmer and his group. After chronic ethanol consumption, the activity of the MEOS increases, with an associated rise in cytochrome P450, especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer mice. There is also cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic metabolites increases, which explains the enhanced susceptibility of alcoholics to the adverse effects of various xenobiotics, including industrial solvents. CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their toxic metabolites, and promotes carcinogenesis. In addition, catabolism of retinol is accelerated resulting in its depletion. Contrasting with the stimulating effects of chronic consumption, acute ethanol intake inhibits the metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a significant release of free radicals which, in turn, diminishes reduced glutathione (GSH) and other defense systems against oxidative stress which plays a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other perivenular P450s, also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role which comprises gluconeogenesis from ketones, oxidation of fatty acids, and detoxification of xenobiotics other than ethanol. Excess of these physiological substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up-regulation was also demonstrated in obese patients as well as in rat models of obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general population, making these conditions the most common liver diseases in the United States. Considering the pathogenic role that up-regulation of CYP2E1 also plays in alcoholic liver disease (vide supra), it is apparent that a major therapeutic challenge is now to find a way to control this toxic process. CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds are too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans (and its active component dilinoleoylphosphatidylcholine), were discovered to decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis. It is now being tested clinically. C1 Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Alcohol Res Ctr, Bronx, NY 10468 USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. NR 117 TC 113 Z9 123 U1 4 U2 24 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD OCT PY 2004 VL 36 IS 3-4 BP 511 EP 529 DI 10.1081/DMR-200033441 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 869CW UT WOS:000224962000011 PM 15554233 ER PT J AU Bouche, C Serdy, S Kahn, CR Goldfine, AB AF Bouche, C Serdy, S Kahn, CR Goldfine, AB TI The cellular fate of glucose and its relevance in type 2 diabetes SO ENDOCRINE REVIEWS LA English DT Review ID ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; PYRUVATE-DEHYDROGENASE KINASE; GLYCOGEN-SYNTHASE KINASE-3; HEXOKINASE-II GENE; CAUSES INSULIN-RESISTANCE; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE ACTIVITY; SELF-GLUCOSYLATING INITIATOR; GAMMA COACTIVATOR-1 PGC-1; TISSUE-SPECIFIC KNOCKOUT AB Type 2 diabetes is a complex disorder with diminished insulin secretion and insulin action contributing to the hyperglycemia and wide range of metabolic defects that underlie the disease. The contribution of glucose metabolic pathways per se in the pathogenesis of the disease remains unclear. The cellular fate of glucose begins with glucose transport and phosphorylation. Subsequent pathways of glucose utilization include aerobic and anaerobic glycolysis, glycogen formation, and conversion to other intermediates in the hexose phosphate or hexosamine biosynthesis pathways. Abnormalities in each pathway may occur in diabetic subjects; however, it is unclear whether perturbations in these may lead to diabetes or are a consequence of the multiple metabolic abnormalities found in the disease. This review is focused on the cellular fate of glucose and relevance to human type 2 diabetes. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [K23-DK02795] NR 313 TC 140 Z9 146 U1 2 U2 17 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2004 VL 25 IS 5 BP 807 EP 830 DI 10.1210/er.2003-0026 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 859PS UT WOS:000224281000004 PM 15466941 ER PT J AU Gelling, RW Overduin, J Morrison, CD Morton, GJ Frayo, RS Cummings, DE Schwartz, MW AF Gelling, RW Overduin, J Morrison, CD Morton, GJ Frayo, RS Cummings, DE Schwartz, MW TI Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feeding SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; NEUROPEPTIDE-Y; CIRCULATING GHRELIN; FOOD-INTAKE; ACYLATED PEPTIDE; GENE-EXPRESSION; INSULIN-TREATMENT; ENERGY-BALANCE; MESSENGER-RNA; RATS AB Plasma levels of the orexigenic hormone, ghrelin, decrease rapidly on nutrient ingestion and yet are paradoxically elevated in rats with hyperphagia induced by streptozotocin-induced diabetes (STZ-DM). In the current work, we investigated the mechanisms underlying the relationships among uncontrolled diabetes, food intake, and plasma ghrelin concentrations in an effort to clarify whether increased ghrelin signaling contributes to diabetic hyperphagia. Whereas food intake did not increase until d 3 after STZ administration, plasma ghrelin levels were increased by more than 2-fold ( P < 0.05) on d 1. As hyperphagia developed, however, plasma ghrelin levels declined steadily. Because this reduction of plasma ghrelin levels was reversed by matching food intake of STZ-DM rats to that of nondiabetic controls, our results demonstrated that the effect of uncontrolled diabetes to increase plasma ghrelin levels is partially offset by hyperphagic feeding. In addition, we found that although intragastric nutrient infusion rapidly and comparably decreased plasma ghrelin levels in both groups ( by 46 - 49%; P < 0.05), this effect was short lived in STZ-DM rats relative to nondiabetic controls ( 60 min vs. 120 min; P< 0.05). We further demonstrated that in rats with STZ-DM, food intake increased by 357% ( P < 0.05) in response to intracerebroventricular administration of ghrelin at a dose that was subthreshold for feeding effects in nondiabetic controls. Collectively, these findings demonstrate that uncontrolled diabetes increases both circulating ghrelin levels and behavioral sensitivity to ghrelin. Although plasma ghrelin levels fall in response to hyperphagic feeding, these findings support the hypothesis that increased ghrelin signaling contributes to the pathogenesis of diabetic hyperphagia. C1 Univ Washington, Harborview Med Ctr, Div Endocrinol, Dept Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Healthcare Syst, Dept Med, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Div Endocrinol, Dept Med, 325 9th Ave,Box 359657, Seattle, WA 98104 USA. EM mschwart@u.washington.edu RI Morrison, Christopher/A-6093-2010; Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK12829, DK52989, DK61516]; NINDS NIH HHS [NS 32273] NR 54 TC 49 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2004 VL 145 IS 10 BP 4575 EP 4582 DI 10.1210/en.2004-0605 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 854FB UT WOS:000223885600020 PM 15256489 ER PT J AU de Lemos, JA Blazing, MA Wiviott, SD Brady, WE White, HD Fox, KAA Palmisano, J Ramsey, KE Bilheimer, DW Lewis, EF Pfeffer, M Califf, RM Braunwald, E AF de Lemos, JA Blazing, MA Wiviott, SD Brady, WE White, HD Fox, KAA Palmisano, J Ramsey, KE Bilheimer, DW Lewis, EF Pfeffer, M Califf, RM Braunwald, E CA A to Z Investigators TI Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial SO EUROPEAN HEART JOURNAL LA English DT Article DE acute coronary syndromes; low molecular weight; heparin; antithrombin; GP IIb/IIIa inhibitors ID ACUTE CORONARY SYNDROMES; MOLECULAR-WEIGHT HEPARIN; GLYCOPROTEIN IIB/IIIA INHIBITION; WAVE MYOCARDIAL-INFARCTION; HIGH-RISK PATIENTS; EFFICACY; SAFETY; THERAPY; EVENTS AB Aims In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant gtycoprotein IIb/IIIa inhibitors. Methods and results The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban. Inclusion required either ST depression or cardiac biomarker elevation. White the selection of an early management strategy (invasive or conservative) was at the discretion of the local investigator, investigators were asked to designate their plans for an invasive or conservative strategy on the case record form. An early conservative strategy was specified for 1778 patients (45%); this subgroup forms the population for the present analyses. Among patients with a planned conservative strategy, baseline characteristics were similar between those randomised to UFH (n = 872) and those randomised to enoxaparin (n = 906). The primary endpoint of death, new MI, or documented refractory ischaemia within 7 days of randomisation occurred in 10.6% of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR 0.72; 95% Cl 0.53-0.99; p = 0.04). The combined rate of TIMI major, minor, or loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those treated with enoxaparin (p = ns). Conclusions When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. Duke Univ, Clin Res Inst, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, Boston, MA 02115 USA. Merck & Co Inc, Whitehouse Stn, NJ USA. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP de Lemos, JA (reprint author), Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, 5323 Harry Hines Blvd,Rm HA9 133, Dallas, TX 75390 USA. EM james.delemos@utsouthwestern.edu NR 17 TC 32 Z9 33 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2004 VL 25 IS 19 BP 1688 EP 1694 DI 10.1016/j/ehj.2004.06.028 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 862UB UT WOS:000224515500006 PM 15451146 ER PT J AU Kashani, A Giugliano, RP Antman, EM Morrow, DA Gibson, CM Murphy, SA Braunwald, E AF Kashani, A Giugliano, RP Antman, EM Morrow, DA Gibson, CM Murphy, SA Braunwald, E TI Severity of heart failure., treatments, and outcomes after fibrinolysis in patients with ST-elevation myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; acute myocardial infarction; STEMI; fibrinolysis; revascularisation; cardiogenic shock ID COMMUNITY-WIDE PERSPECTIVE; TIMI RISK SCORE; CARDIOGENIC-SHOCK; EARLY REVASCULARIZATION; NATIONAL-REGISTRY; THROMBOLYTIC THERAPY; SEGMENT ELEVATION; CLINICAL OUTCOMES; INTRAVENOUS NPA; TEMPORAL TRENDS AB Aims To define the clinical characteristics, co-morbidities, treatment, and clinical outcomes of patients with varying degrees of heart failure (HF) complicating ST-elevation myocardial infarction (STEMI), and to identify patients at high risk for HF following fibrinolysis. Methods and results 15,078 STEMI patients enrolled in a worldwide fibrinolytic trial (InTIME-II) were categorised into one of four hierarchical, mutually exclusive groups of HF: shock (n = 719, 5%); severe HF (n = 1082, 7%); mild HF (n = 1619, 11 %); no HF (n = 11, 658, 77%). In a multivariable model, anterior MI (OR 1.8, 95% Cl [1.6; 1.9]), age greater than or equal to65 (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance <60 mL/min (OR 1.8 [1.6; 2.1]) were the four most powerful correlates of HF. Although 30-day mortality was sixfold higher for patients with HF (18.9% vs. 3.1% p < 0.0001), these patients were less likely to undergo angiography (30% vs. 40%, p < 0.0001) and revascularisation (19% vs. 25%, p < 0.0001), than patients without HF. Likewise, angiotensin-inhibitors and beta-blockers were not optimally utilised in patients with HF following MI. Conclusions During the index admission following fibrinolysis 23% of patients had HF. Despite a higher risk profile, patients with more severe HF were treated less aggressively than patients without HF. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Rochester Gen Hosp, Dept Internal Med, Rochester, NY 14621 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 35 TC 18 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2004 VL 25 IS 19 BP 1702 EP 1710 DI 10.1016/j.ehj.2004.05.009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 862UB UT WOS:000224515500008 PM 15451148 ER PT J AU Ferlin, WG Mougneau, E Hugues, S Appel, H Jang, MH Cazareth, J Beaudoin, L Schricke, C Lehuen, A Wucherpfennig, KW Glaichenhaus, N AF Ferlin, WG Mougneau, E Hugues, S Appel, H Jang, MH Cazareth, J Beaudoin, L Schricke, C Lehuen, A Wucherpfennig, KW Glaichenhaus, N TI Self-peptides that bind with low affinity to the diabetes-associated I-A(g7) molecule readily induce T cell tolerance in non-obese diabetic mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE major histocompatibility complex; autoimmunity; peripheral tolerance; central tolerance ID CLASS-II MOLECULE; LEISHMANIA-MAJOR; ANTIGEN; MHC; EXPRESSION; NOD; SUSCEPTIBILITY; ACTIVATION; DISEASE; MOUSE AB Although non-obese diabetic (NOD) mice spontaneously develop T cell autoimmunity, it is not clear whether this phenomenon results from a defect in tolerance to self-Ag. Furthermore, as autoimmunity has been postulated to result from T cell responses directed toward self-peptides that bind with low affinity to NOD I-A(g7) MHC class 11 molecules, it is important to determine whether the expression of such peptides induces tolerance. We have constructed NOD transgenic (Tg) mice expressing the Leishmania antigen receptor for C kinase (LACK) Ag in either the thymus or pancreatic P cells. We identified LACK peptides that were the targets of T cells in LACK-immunized NOD mice while binding to I-A 97 with low affinity. While CD4(+) T cells from NOD mice secreted IFN-gamma, IL-4, IL-5 and IL-10 in response to LACK, those from LACK-expressing Tg mice secreted reduced levels of cytokines. Experiments using peptide/MHC multimers showed that LACK-expressing Tg mice exhibited self-reactive CD4(+) T cells with impaired proliferation capabilities. Hence, even self-peptides that bind to I-A (g7) with low affinity can induce tolerance in NOD mice. This result is important in light of the commonly held hypothesis that T cells reacting to peptides that bind to MHC with low affinity escape tolerance induction and cause autoimmunity. C1 Univ Nice Sophia Antipolis, INSERM E0344, F-06560 Valbonne, France. Hop Necker Enfants Malad, INSERM, U25, Paris, France. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Glaichenhaus, N (reprint author), Univ Nice Sophia Antipolis, INSERM E0344, 660 Route Lucioles, F-06560 Valbonne, France. EM glaichenhaus@ipmc.cnrs.fr NR 31 TC 6 Z9 6 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2004 VL 34 IS 10 BP 2656 EP 2663 DI 10.1002/eji.200425413 PG 8 WC Immunology SC Immunology GA 862UX UT WOS:000224517800004 PM 15368281 ER PT J AU Hu, J Mata, M Hao, SL Zhang, G Fink, DJ AF Hu, J Mata, M Hao, SL Zhang, G Fink, DJ TI Central sprouting of uninjured small fiber afferents in the adult rat spinal cord following spinal nerve ligation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE neural plasticity; neuropathic; pain; spinal nerve ligation; sprouting ID DORSAL-ROOT GANGLION; CHOLERAGENOID-HORSERADISH-PEROXIDASE; PRIMARY SENSORY NEURONS; GENE-RELATED PEPTIDE; SCIATIC-NERVE; NEUROPATHIC PAIN; PERIPHERAL-NERVE; TRANSGANGLIONIC TRANSPORT; SOMATOTOPIC ORGANIZATION; SUBSTANTIA-GELATINOSA AB Partial nerve injury results in chronic pain that is difficult to treat effectively. To investigate the anatomic basis of this phenomenon we used wheat germ agglutinin-horseradish peroxidase (WGA-HRP) to label the central projections of uninjured small fibers (Adelta and C) in a well-established model of neuropathic pain created by selective spinal nerve ligation in the adult. We found extensive sprouting of uninjured WGA-HRP-labeled afferents into the central termination field in lamina II of dorsal horn normally occupied by L5 afferents whose peripheral axons had been ligated distal to the dorsal root ganglion. The formation of new projections by uninjured fibers into a functionally but not anatomically deafferented field in the adult may play a role in the development of chronic pain. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. Ann Arbor VA Healthcare Syst, Ann Arbor, MI 48109 USA. RP Fink, DJ (reprint author), 1914 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM djfink@umich.edu NR 53 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2004 VL 20 IS 7 BP 1705 EP 1712 DI 10.1111/j.1460-9568.2004.03652.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 855TJ UT WOS:000223996900002 PM 15379991 ER PT J AU Sala, M Perez, J Soloff, P di Nemi, SU Caverzasi, E Soares, JC Brambilla, P AF Sala, M Perez, J Soloff, P di Nemi, SU Caverzasi, E Soares, JC Brambilla, P TI Stress and hippocampal abnormalities in psychiatric disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE posttraumatic stress disorder; borderline personality disorder; depression; MRI; MRS; PET ID BORDERLINE PERSONALITY-DISORDER; CHILDHOOD SEXUAL-ABUSE; CA3 PYRAMIDAL NEURONS; PROTEIN-KINASE-A; ELEMENT-BINDING PROTEIN; LONG-TERM-MEMORY; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PROLONGED GLUCOCORTICOID EXPOSURE; MAGNETIC-RESONANCE SPECTROSCOPY; PITUITARY-ADRENOCORTICAL AXIS AB The hippocampus plays a main role in regulating stress response in humans, but is itself highly sensitive to neurotoxic effects of repeated stressful episodes. Hippocampal atrophy related to experimental stress has been reported in laboratory studies in animals. Several controlled brain imaging studies have also shown hippocampal abnormalities in psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and borderline personality disorder (BPD). This paper reviews the physiological role of the hippocampus in stress circuitry and the effects of stress on cognitive functions mediated by the hippocampus. We also review brain imaging studies investigating hippocampus in PTSD, MDD, and BPD. This literature suggests that individuals with PTSD, MDD, and BPD may suffer hippocampal atrophy as a result of stressors associated with these disorders. Prospective, longitudinal studies will be needed in high-risk offspring and first-episode subjects to explore the relationship between stress and hippocampal atrophy in these neuropsychiatric illnesses. (C) 2004 Elsevier B.V. and ECNP. All rights reserved. C1 Univ Pavia, Policlin San Matteo, IRCCS, Dept Psychiat,Sch Med, I-27100 Pavia, Italy. IRCCS S Giovanni Dio, Biol Psychiat Unit, I-25125 Brescia, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Brambilla, P (reprint author), Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. EM brambillapf@tiscali.it RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH048463] NR 160 TC 88 Z9 98 U1 6 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 IS 5 BP 393 EP 405 DI 10.1016/j.euroneuro.2003.12.005 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 856BJ UT WOS:000224018300008 PM 15336301 ER PT J AU Allen, AJ Kurlan, RM Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, DW Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ AF Allen, AJ Kurlan, RM Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, DW Sallee, FR Milton, DR Mintz, MI Ricardi, RK Erenberg, G Layton, LL Feldman, PD Kelsey, DK Spencer, TJ TI Atomoxetine treatment in children with attention-deficit/hyperactivity disorder and comorbid tic disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14627 USA. Dallas Pediat Neurol Associates, Dallas, TX USA. Monarch Res Associates, Norfolk, VA USA. Premiere Res Inst, W Palm Beach, FL USA. Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA. Bancroft Neurohlth, Cherry Hill, NJ USA. Riley Child & Adolescent Psychiat Clin, Indianapolis, IN USA. Arizona Family Resource Counseling Ctr, Phoenix, AZ USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S373 EP S373 DI 10.1016/S0924-977X(04)80543-1 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400545 ER PT J AU Biederman, J Mick, E Faraone, SV AF Biederman, J Mick, E Faraone, SV TI 10 year follow-up study of males with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S370 EP S370 DI 10.1016/S0924-977X(04)80536-4 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400538 ER PT J AU Biederman, J Swanson, JM Boellner, SW Lopez, E AF Biederman, J Swanson, JM Boellner, SW Lopez, E TI Modafinil as therapy for ADHD in children: A 4-week, double-blind, placebo-controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol ID DISORDER C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. Neurol & Clin Study Ctr, Little Rock, AR USA. Childrens Dev Ctr, Dept Neurodev Pediat, Maitland, FL USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S364 EP S364 DI 10.1016/S0924-977X(04)80522-4 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400524 ER PT J AU Biederman, J Mick, E AF Biederman, J Mick, E TI Treatment of preschoolers with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S212 EP S212 DI 10.1016/S0924-977X(04)80178-0 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400179 ER PT J AU Biederman, J Mick, E AF Biederman, J Mick, E TI Comparative open-label trial of atypical neuroleptics in children and adolescents with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S211 EP S212 DI 10.1016/S0924-977X(04)80177-9 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400178 ER PT J AU Biederman, J AF Biederman, J TI Is pediatric mania a developmental subtype of bipolar disorder? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol ID ADOLESCENTS; CHILDHOOD; CHILDREN; ILLNESS; ONSET; SYMPTOMS; RELAPSE C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S137 EP S137 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400042 ER PT J AU Buitelaarl, JK Michelson, D Danckaerts, M Gillberg, C Spencer, T Zuddas, A Faries, D Zhang, S Biederman, J AF Buitelaarl, JK Michelson, D Danckaerts, M Gillberg, C Spencer, T Zuddas, A Faries, D Zhang, S Biederman, J TI Continued atomoxetine in pediatric patients with attention-deficit hyperactivity disorder after 1 year of treatment SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Univ Med Ctr St Radboud, Dept Psychiat, Nijmegen, Netherlands. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Katholieke Univ Leuven, Louvain, Belgium. Barnneuropsykiat Kliniken, Gothenburg, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Neuropsichiatria Infantile, Cagliari, Italy. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S372 EP S372 DI 10.1016/S0924-977X(04)80541-8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400543 ER PT J AU Fava, M Schutte, AJ Willigenburg, APP AF Fava, M Schutte, AJ Willigenburg, APP TI Efficacy of mirtazapine vs. SSRIs in anxiety symptoms associated with major depression: A pooled data analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Depress Res Program, Boston, MA 02114 USA. Organon Int Inc, Med Serv, Roseland, NJ USA. NV Organon, Med Serv, Oss, Netherlands. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S187 EP S188 DI 10.1016/S0924-977X(04)80123-8 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400124 ER PT J AU Grunze, H Carson, W Sachs, G Sanchez, R Marcus, R Kujawa, M Archibald, D Iwamoto, T AF Grunze, H Carson, W Sachs, G Sanchez, R Marcus, R Kujawa, M Archibald, D Iwamoto, T TI Aripiprazole treatment for acute mania in patients with bipolar I disorder: A placebo-controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Univ Munich, Munich, Germany. Otsuka Amer Pharmaceut Inc, Princeton, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Otsuka Pharmaceut Co Ltd, Tokyo, Japan. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S264 EP S264 DI 10.1016/S0924-977X(04)80292-X PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400294 ER PT J AU Khan, A Montgomery, SA Simon, N Farfel, G Tobias, K Zornberg, GL AF Khan, A Montgomery, SA Simon, N Farfel, G Tobias, K Zornberg, GL TI Pregabalin in the treatment of core depressive symptoms in generalized anxiety disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 NW Clin Res Ctr, Bellevue, WA USA. Imperial Coll Sch Med, Dept Pharmacol, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, Global Pharmaceut, New York, NY USA. Pfizer Inc, Global Res & Dev, Ann Arbor, MI USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S319 EP S319 DI 10.1016/S0924-977X(04)80416-4 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400418 ER PT J AU Mick, E Biederman, J Faraone, SV AF Mick, E Biederman, J Faraone, SV TI 5 Year follow-up study of females with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S370 EP S371 DI 10.1016/S0924-977X(04)80537-6 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400539 ER PT J AU Mick, E Biederman, J AF Mick, E Biederman, J TI Treatment of psychotic symptoms in children and adolescents with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S270 EP S270 DI 10.1016/S0924-977X(04)80307-9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400309 ER PT J AU Mick, E Biederman, J AF Mick, E Biederman, J TI Effectiveness of risperidone for the treatment of ADHD in children and adolescents with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S212 EP S213 DI 10.1016/S0924-977X(04)80179-2 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400180 ER PT J AU Parikh, RM Sonawalla, SB Fava, M Chakraborthy, N Mehra, G Dracass, S AF Parikh, RM Sonawalla, SB Fava, M Chakraborthy, N Mehra, G Dracass, S TI Depression and suicidal ideation among college students in Bombay: A study of 1357 individuals SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Jaslok Hosp & Res Ctr, Bombay, Maharashtra, India. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S231 EP S231 DI 10.1016/S0924-977X(04)80217-7 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400219 ER PT J AU Pollack, MH Kasper, S Cohn, CK Farfel, G Zornberg, GL AF Pollack, MH Kasper, S Cohn, CK Farfel, G Zornberg, GL TI Efficacy of pregabalin in clinically relevant subtypes of generalized anxiety disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Vienna, Dept Gen Psychiat, Vienna, Austria. Fein Jennings Clin Inc, Houston, TX USA. Pfizer Inc, New York, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S320 EP S320 DI 10.1016/S0924-977X(04)80418-8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400420 ER PT J AU Sonawalla, SB Beaumont, E Mahal, Y Iosifescu, D Mischoulon, D Alpert, JE Fava, M AF Sonawalla, SB Beaumont, E Mahal, Y Iosifescu, D Mischoulon, D Alpert, JE Fava, M TI Depressive symptoms and suicidal ideation among college students: A study of 752 students in the Boston area SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S230 EP S231 DI 10.1016/S0924-977X(04)80216-5 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400218 ER PT J AU Spencer, T Biederman, J Mick, E Faraone, SV AF Spencer, T Biederman, J Mick, E Faraone, SV TI Efficacy in a 6 month trial of methylphenidate in adults with attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S369 EP S369 DI 10.1016/S0924-977X(04)80533-9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400535 ER PT J AU Swindle, RW Mallinckrodt, CH Rosenbaum, JE Lu, Y Watkin, JG Gandhi, P Detke, MJ AF Swindle, RW Mallinckrodt, CH Rosenbaum, JE Lu, Y Watkin, JG Gandhi, P Detke, MJ TI Efficacy of duloxetine treatment: Analysis of pooled data from six placebos and SSRI-controlled clinical trials SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S190 EP S190 DI 10.1016/S0924-977X(04)80129-9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400130 ER PT J AU Thase, ME DeBattista, C Fava, M AF Thase, ME DeBattista, C Fava, M TI Modafinil as antidepressant augmentation therapy in major depressive disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 17th Congress of the European-College-of-Neuropsychopharmacology CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2004 VL 14 SU 3 BP S210 EP S211 DI 10.1016/S0924-977X(04)80175-5 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 875YX UT WOS:000225460400176 ER PT J AU Huang, WB Carlsen, B Wulur, I Rudkin, G Ishida, K Wu, B Yamaguchi, DT Miller, TA AF Huang, WB Carlsen, B Wulur, I Rudkin, G Ishida, K Wu, B Yamaguchi, DT Miller, TA TI BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE bone marrow stromal cell; BMP; PLGA; two-dimensional; three-dimensional; bone formation; osteogenic differentiation ID MORPHOGENETIC PROTEIN-2 INCREASES; MESENCHYMAL STEM-CELLS; OSTEOBLASTIC CELLS; REGENERATION; VIVO; ANGIOGENESIS; BIOMATERIALS; EXPRESSION; COLLAGEN; CARRIER AB Osteogenic differentiation of bone marrow stromal cells (BMSC) in a three-dimensional (3-D) scaffold has not been well studied. In this work, we studied expression of bone-related genes during differentiation of rabbit BMSCs in response to bone morphogenetic protein (BMP)-2 in both 2-D and 3-D culture systems. When BMSCs were cultured on films (2-D) of biodegradable poly(lactide-co-glycolide) (PLGA), increases in mRNA expression of type I collagen (Col 1) and vascular endothelial growth factor (VEGF) became evident after I week. However, expression of both genes was only mildly stimulated by BMP-2. Expression of the osteopontin gene was highly stimulated by BMP-2 treatment. Expression of chordin, a BMP antagonist, increased significantly after 7 days. The increase was abrogated by BMP-2 treatment. BMP-2 was also able to stimulate mineralization of cultured BMSCs. After cells were switched to 3-D PLGA scaffolds for 24 h, expression of osteopontin and VEGF were markedly increased while expression of type I collagen and chordin remained unchanged. Expression of Col I did not increase with time in a 3-D culture as it did when cells were cultured on a 2-D film. We further explored the possibility of engineering bone tissue in vitro by seeding BMSCs into PLGA scaffolds. Cellular differentiation and bone formation in the scaffolds were analyzed histologically at 2 weeks and 2 months. Secretion of ECM by cells was evident at both 2-week and 2-month scaffolds, and was enhanced by rhBMP-2. Striking differences in 2-month scaffolds were observed between BMP-treated and untreated cells. A woven bone-like structure appeared in the scaffolds treated with BMP-2. The structure was verified to be bone-related by: (1) the presence of organized collagen fibrils; (2) the presence of mineral; and (3) morphological features of trabecular bone. Although collagen was abundant in the untreated 2-month scaffolds, it was disorganized. The untreated scaffolds also lacked mineral deposits, which were present in 2-D cultured cells even in the absence of BMP-2. Our results indicate that the requirement of osteo-inductive agents, such as BMP-2, is essential for bone tissue engineering. (C) 2004 Published by Elsevier Inc. C1 VA Greater LA Healthcare Syst, Plast Surg Lab, Plast Surg Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Surg, Div Plast Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biomed Engn, Los Angeles, CA 90095 USA. RP Miller, TA (reprint author), VA Greater LA Healthcare Syst, Plast Surg Lab, Plast Surg Sect, Room 221,Bldg 114,11301 Wilts Blvd, Los Angeles, CA 90073 USA. EM millerlab@hotmail.com NR 39 TC 78 Z9 94 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 1 PY 2004 VL 299 IS 2 BP 325 EP 334 DI 10.1016/j.yexcr.2004.04.051 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 855AW UT WOS:000223946300007 PM 15350532 ER PT J AU Hamrah, P Chen, L Cursiefen, C Zhang, Q Joyce, NC Dana, MR AF Hamrah, P Chen, L Cursiefen, C Zhang, Q Joyce, NC Dana, MR TI Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) on monocytic bone marrow-derived cells in the conjunctiva SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE VEGFR-3; conjunctiva; monocytes; lymphangiogenesis ID CD34(+) HEMATOPOIETIC PROGENITORS; CORD-BLOOD DIFFERENTIATE; ANGIOGENESIS IN-VIVO; FACTOR-C; LYMPHATIC ENDOTHELIUM; PERMEABILITY FACTOR; CORNEAL NEOVASCULARIZATION; TUMOR LYMPHANGIOGENESIS; MACROPHAGE RECRUITMENT; TYROSINE KINASES AB Vascular endothelial growth factor-3 (VEGFR-3), also known as Fms-like tyrosine kinase receptor 4 (FLT-4), was thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on vascular endothelium. It plays a critical role in the development of lymphatics and cancer metastasis. Very recently, however, VEGFR-3 expression has been identified on dendritic cells (DCs) in the inflamed cornea, and related to the trafficking of these cells to lymphoid organs. The current study was performed to evaluate the expression of VEGFR-3 in the conjunctiva. The conjunctiva and limbus of normal and inflamed murine eyes were excised and stained for VEGFR-3. Immunofluorescense double staining for CD11b, CD11c, CD31, CD45, GR-1, CD3, CD80, LYVE-I and class II major histocompatibility complex (MHC) antigen expression, using confocal microscopy, was performed to further phenotype the VEGFR-3(+) cells. VEGFR-3 and LYVE-I expression was observed on lymphatic, but not blood vessel, endothelium. In addition, we also detected expression of VEGFR-3 on non-endothelial CD45(+) bone marrow-derived cells in the conjunctiva of normal and, in an increased number, in inflamed eyes. These cells were uniformly CD11b(+), CD3(-), and Gr-1(-),suggesting a monocytic origin, similar to the VEGFR-3(+) cells in the cornea. Nearly half of the VEGFR-3(+) cells were also positive for MHC class II expression, and none were positive for CD80 (B7-1), indicating their relative immature status. In contrast to the recently described VEGFR3(+) corneal cells, however, VEGFR-3(+) conjunctival cells did not express the DC marker CD11c. We conclude that in addition to its known role in lymphangiogenesis, VEGFR-3 is also expressed by a conjunctival monocyte/macrophage lineage, implicating a potential relationship between lymphangiogenesis and leukocyte trafficking in the ocular surface. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, 20 Staniford St, Boston, MA 02114 USA. EM pedram.hamrah@louisville.edu; dana@vision.eri.harvard.edu FU NEI NIH HHS [EY-12963] NR 56 TC 34 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2004 VL 79 IS 4 BP 553 EP 561 DI 10.1016/j.exer.2004.06.028 PG 9 WC Ophthalmology SC Ophthalmology GA 860YF UT WOS:000224379800011 PM 15381039 ER PT J AU Lieberman, D Fennerty, MB Morris, CD Holub, J Eisen, G Sonnenberg, A AF Lieberman, D Fennerty, MB Morris, CD Holub, J Eisen, G Sonnenberg, A TI Endoscopic evaluation of patients with dyspepsia: Results from the national endoscopic data repository SO GASTROENTEROLOGY LA English DT Article ID BARRETTS-ESOPHAGUS; GASTROESOPHAGEAL REFLUX; UNCOMPLICATED DYSPEPSIA; WORKING PARTY; MANAGEMENT; MALIGNANCY; DIAGNOSIS; THERAPY AB Background & Aims: Endoscopy is commonly performed to evaluate symptoms of dyspepsia. The aim of this study was to characterize patients who receive endoscopy for dyspepsia and measure predictors of primary endoscopic outcomes, utilizing a large national endoscopic database. Methods: The Clinical Outcomes Research Initiative (CORI) receives endoscopy reports from a network of 74 sites in the United States. Sixty-one percent of reports come from private practice settings. Patients with reflux dyspepsia and nonreflux dyspepsia were identified from January 2000 to June 2002. Patients with dysphagia and known Barrett's esophagus were excluded. Primary endoscopic outcomes included esophageal inflammation and stricture, gastric ulcer, duodenal ulcer, suspected Barrett's esophagus (greater than or equal to2cm), and suspected esophageal and gastric malignancy. The presence or absence of alarm symptoms (vomiting, weight loss, and evidence of GI blood loss) was determined. Adjusted relative risk (RR) for predicting serious outcomes was calculated in a multivariate model. Results: We received 117,497 endoscopic reports, representing 99,558 unique patients. Dyspepsia, with and without reflux symptoms, accounted for 43% of upper endoscopies. Among dyspeptic patients, 36.5% were younger than 50 years of age without alarm symptoms. Esophageal or gastric malignancy in patients with dyspepsia was associated with increasing age, male sex, Asian race, Native American race, and symptoms of weight loss and vomiting. Suspected Barrett's esophagus (greater than or equal to2cm) was associated with reflux symptoms, male sex, age, and white race. Ulcers were associated with evidence of bleeding, vomiting, male sex, black race, and Hispanic ethnicity. Conclusions: These practice-based data reveal important practice behaviors and outcomes. C1 Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA. EM lieberma@ohsu.edu FU NCI NIH HHS [U01 CA 89389-01]; NIDDK NIH HHS [R33-DK61778-01] NR 20 TC 65 Z9 67 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2004 VL 127 IS 4 BP 1067 EP 1075 DI 10.1053/j.gastro.2004.07.060 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 864AG UT WOS:000224604400012 PM 15480985 ER PT J AU Hirokawa, M Takeuchi, T Chu, S Akiba, Y Wu, V Guth, PH Engel, E Montrose, MH Kaunitz, JD AF Hirokawa, M Takeuchi, T Chu, S Akiba, Y Wu, V Guth, PH Engel, E Montrose, MH Kaunitz, JD TI Cystic fibrosis gene mutation reduces epithelial cell acidification and injury in acid-perfused mouse duodenum SO GASTROENTEROLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; APICAL CL-/HCO3-EXCHANGER; PEPTIC-ULCER DISEASE; BICARBONATE SECRETION; INTRACELLULAR PH; ALKALINE SECRETION; GASTROINTESTINAL-TRACT; MUCOSAL PERMEABILITY; HYDROCHLORIC-ACID; INDUCED INCREASE AB Background & Aims: Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) is associated with diminished duodenal HCO3- secretion, despite a reported lack of clinical duodenal ulceration in affected subjects. We hypothesized that duodenal epithelial cells expressing a mutant CFTR have enhanced resistance to acid-induced injury. To test this hypothesis, we measured duodenal epithelial cell intracellular pH (pH(i)), injury, and acid back-diffusion in response to a luminal acid challenge in transgenic mice. Methods: A murine colony was established for the CFTR DeltaF508 (DeltaF) mutation. Epithelial cell pH(i) was measured by microscopy with a trapped, fluorescent pH-sensitive dye in living C57BL/6 and DeltaF/ DeltaF, +/DeltaF, and +/+ mice. In vivo confocal microscopy confirmed the localization of the dye in the cytoplasm of the epithelial cells. Epithelial injury was measured fluorometrically using propidium iodide. Duodenal epithelial bicarbonate secretion and proton permeability were measured by back-titration. Bicarbonate secretion and acid back-diffusion were measured in a perfused duodenal loop. Results: Basal and post-acid exposure bicarbonate secretion were reduced in DeltaF/DeltaF mice, although acid back-diffusion was similar to controls. Epithelial pHi of CFTR DeltaF/DeltaF mice during luminal acid exposure was significantly higher than pH(i) in +/DeltaF, +/+, or C57BL/6 mice. Acid-related epithelial injury was markedly less in DeltaF/DeltaF mice in comparison with the other groups. Conclusions: Increased cellular buffering power of the epithelial cells of DeltaF/DeltaF mice likely protects against acidification and injury during acid exposure. We speculate that this protective mechanism partially underlies the perceived relative lack of peptic ulceration in patients affected by cystic fibrosis. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Dept Digest Dis, Sch Med,CURE, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90024 USA. Indiana Univ, Sch Med, Dept Cellular & Intergrat Physiol, Indianapolis, IN 46204 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [DK54221, R01 DK054940, DK54940] NR 74 TC 23 Z9 25 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2004 VL 127 IS 4 BP 1162 EP 1173 DI 10.1053/j.gastro.2004.06.057 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 864AG UT WOS:000224604400021 PM 15480994 ER PT J AU MacIntosh, DG Love, J Abraham, NS AF MacIntosh, DG Love, J Abraham, NS TI Endoscopic sphincterotomy by using pure-cut electrosurgical current and the risk of post-ERCP pancreatitis: a prospective randomized trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/104th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-22, 2003 CL ORLANDO, FL SP Amer Gastroenterol Assoc ID COMPLICATIONS; MULTICENTER AB Background: It has been suggested that the use of pure-cut electrosurgical current for endoscopic sphincterotomy may reduce the risk of post-ERCP pancreatitis. The aim of this study was to determine whether pure-cut current reduces the risk of pancreatitis compared with blend current. Methods: Patients were randomly assigned to undergo sphincterotomy over a non-conductive guidewire with 30 W/sec pure-cut current or 30 W/sec blend-2 current by a blinded endoscopist. Serum amylase and lipase levels were determined 1 day before and within 24 hours after ERCP. Post-ERCP pancreatitis was the primary outcome of interest. Secondary outcomes were as follows: severity of immediate bleeding, as graded by a 3-point scale from 1 (no bleeding) to 3 (injection or balloon tamponade therapy required to stop bleeding) and evidence of delayed bleeding 24 hours after ERCP. Analyses were performed in intention-to-treat fashion. Results: A total of 246 patients were randomized (116 pure-cut current, 130 blend current). There were no differences in baseline characteristics between the groups. The overall frequency of post-ERCP pancreatitis was 6.9%, with no significant difference in frequency between treatment arms (pure cut, 7.8% vs. blend, 6.1%; p = 0.62). The difference in rates of pancreatitis between the two groups was 1.7%: 95% CI[-4.8%, 8.2%]. Six patients (2.4%) had delayed bleeding after ERCP, of which two required transfusion. There was a significant increase in minor bleeding episodes (grade 2) in the pure-cut group (p < 0.0001). Delayed episodes of bleeding were equal (n = 3) in each arm. Conclusions: The type of current used when performing endoscopic sphincterotomy does not appear to alter the risk of post-ERCP pancreatitis. The selection of electrosurgical current for biliary endoscopic sphincterotomy should be based on endoscopist preference. C1 Dalhousie Univ, Div Gastroenterol, Halifax, NS, Canada. Vet Affairs Med Ctr, Hlth Serv Res, Houston, TX 77030 USA. Vet Affairs Med Ctr, Dept Hlth Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 12 TC 23 Z9 24 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2004 VL 60 IS 4 BP 551 EP 556 AR PII S0016-5107(04)01917-0 DI 10.1016/S0016-5107(04)01917-0 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 864LO UT WOS:000224635200009 PM 15472677 ER PT J AU MacLean, HE Kronenberg, HM AF MacLean, HE Kronenberg, HM TI Expression of Stra13 during mouse endochondral bone development SO GENE EXPRESSION PATTERNS LA English DT Article DE Stra13; DEC1; bHLH; chondrocyte; cartilage; endochondral bone; hypoxia; VEGF; HlFl-alpha ID GROWTH ARREST; DIFFERENTIATION; PROTEIN; CHONDROCYTES; CARTILAGE; HYPOXIA; DEC1; TRANSCRIPTION AB We have examined the expression of the basic helix-loop-helix factor Stra13 (DEC1/Sharp2) during endochondral bone development in the mouse. Stra13 expression was examined by in situ hybridization in the tibia from E14.5-E18.5, and at post-natal day 24. At E14.5, expression of Stra13 mRNA was very low, with expression limited to scattered hypertrophic chondrocytes. At E15.5 Stra13 mRNA was present in post-mitotic hypertrophic chondrocytes, co-localizing with collagen X expression. At E16.5-E18.5, Stra13 was expressed in both the proliferating chondrocytes and in the late hypertrophic chondrocytes. At E15.5-E18.5, Stra13 expression was also observed in the primary spongiosa. Stra13 expression was also maintained in the 24-day post-natal tibia, with expression detectable only in the late hypertrophic chondrocytes. Because Stra13 has been shown to be induced by hypoxia, and the growth plate is hypoxic during embryonic development, we compared the expression pattern of Stra13 and the HIF1-alpha target gene VEGF. VEGF is expressed predominantly in the late hypertrophic chondrocytes, with lower expression in the proliferating chondrocytes. Thus, there was a large degree of overlap in the expression patterns of Stra13 and VEGF in chondrocytes during embryonic development. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, WEL501,50 Blossom St, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU NIDDK NIH HHS [DK-56246] NR 14 TC 6 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD OCT PY 2004 VL 4 IS 6 BP 633 EP 636 DI 10.1016/j.modgep.2004.04.011 PG 4 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 865CP UT WOS:000224680400003 PM 15465485 ER PT J AU Hock, H Meade, E Medeiros, S Schindler, JW Valk, PJM Fujiwara, Y Orkin, SH AF Hock, H Meade, E Medeiros, S Schindler, JW Valk, PJM Fujiwara, Y Orkin, SH TI Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival SO GENES & DEVELOPMENT LA English DT Article DE Ets; hematopoietic stem cell; megakarvocyte; Cre/loxP; Tel/Etv6 ID MICE LACKING; BONE-MARROW; IN-VIVO; GENE; LEUKEMIA; DEFECT; BMI-1; PROLIFERATION; MAINTENANCE; PROTEIN AB Hematopoietic stem cells (HSCs) sustain blood formation throughout life. Pathways regulating maintenance of adult HSCs are largely unknown. Here we report that the Ets-related transcription factor Tel/Etv6, the product of a locus frequently involved in translocations in leukemia, is a selective regulator of HSC survival. Following inactivation of Tel/Etv6, HSCs are lost in the adult bone marrow but their progeny are unaffected and transiently sustain blood formation. Accordingly, absence of Tel/Etv6 after lineage commitment is ostensibly without consequence except for unexpected impairment of maturation of megakaryocytes. Thus, we establish Tel/Etv6 as a selective and essential regulator of postembryonic HSCs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU NCI NIH HHS [K08 CA096701, 1 K08 CA096701-01] NR 31 TC 134 Z9 137 U1 1 U2 4 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 OCT 1 PY 2004 VL 18 IS 19 BP 2336 EP 2341 DI 10.1101/gad.1239604 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 858MT UT WOS:000224196600002 PM 15371326 ER PT J AU Brasch, MA Hartley, JL Vidal, M AF Brasch, MA Hartley, JL Vidal, M TI ORFeome cloning and systems biology: Standardized mass production of the parts from the parts-list SO GENOME RESEARCH LA English DT Editorial Material ID GREEN FLUORESCENT PROTEIN; SACCHAROMYCES-CEREVISIAE GENOME; SITE-SPECIFIC RECOMBINATION; DOUBLE-STRANDED-RNA; CAENORHABDITIS-ELEGANS; C-ELEGANS; ESCHERICHIA-COLI; INTERACTION MAP; FUNCTIONAL-ORGANIZATION; DROSOPHILA-MELANOGASTER C1 Harvard Univ, Sch Med, 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. Atto Biosci, Rockville, MD 20850 USA. NCI, SAIC, Frederick, MD 21702 USA. RP Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu NR 85 TC 49 Z9 54 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2001 EP 2009 DI 10.1101/gr.2769804 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000001 PM 15489318 ER PT J AU Hill, DE Brasch, MA del Campo, AA Doucette-Stamm, L Garrels, JI Glaven, J Hartley, JL Hudson, JR Moore, T Vidal, M AF Hill, DE Brasch, MA del Campo, AA Doucette-Stamm, L Garrels, JI Glaven, J Hartley, JL Hudson, JR Moore, T Vidal, M TI Academia-industry collaboration: An integral element for building "omic" resources SO GENOME RESEARCH LA English DT Editorial Material ID HUMAN-GENOME-PROJECT; DOUBLE-STRANDED-RNA; CAENORHABDITIS-ELEGANS; GENETIC INTERFERENCE; SACCHAROMYCES-CEREVISIAE; BETA-GLOBIN; C-ELEGANS; DNA; EXPRESSION; MICROARRAY C1 Harvard Univ, Sch Med, 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. Atto Biosci, Rockville, MD 20850 USA. Dana Farber Canc Inst, Off Res & Technol Ventures, Boston, MA 02115 USA. Agencourt BIosci Corp, Beverly, MA 01915 USA. NCI, SAIC, Frederick, MD 21702 USA. CityScapes, Huntsville, AL 35801 USA. Open Biosyst, Huntsville, AL 35806 USA. RP Hill, DE (reprint author), Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM david_hill@dfci.harvard.edu RI Hill, David/B-6617-2011 NR 57 TC 0 Z9 0 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2010 EP 2014 DI 10.1101/gr.2771404 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000002 PM 15489319 ER PT J AU Lamesch, P Milstein, S Hao, T Rosenberg, J Li, N Sequerra, R Bosak, S Doucette-Stamm, L Vandenhaute, J Hill, DE Vidal, M AF Lamesch, P Milstein, S Hao, T Rosenberg, J Li, N Sequerra, R Bosak, S Doucette-Stamm, L Vandenhaute, J Hill, DE Vidal, M TI C-elegans ORFeome version 3.1: Increasing the coverage of 2064 ORFeome resources with improved gene predictions SO GENOME RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; GENOME; CLONING AB The first version of the Caenorhabditis elegans ORFeome cloning project, based on release WS9 of Wormbase (August 1999), provided experimental verifications for similar to55% of predicted protein-encoding open reading frames (ORFs). The remaining 45% of predicted ORFs could not be cloned, possibly as a result of mispredicted gene boundaries. Since the release of WS9, gene predictions have improved continuously. To test the accuracy of evolving predictions, we attempted to PCR-amplify from a highly representative worm cDNA library and Gateway-clone similar to4200 ORFs missed earlier and for which new predictions are available in WS100 (May 2003). In this set we successfully cloned 63% of ORFs with supporting experimental data ("touched" ORFs), and 42% of ORFs with no supporting experimental evidence ("untouched" ORFs). Approximately 2000 full-length ORFs were cloned in-frame, 13% of which were corrected in their exon/intron structure relative to WS100 predictions. In total, similar to12,500 C. elegans ORFs are now available as Gateway Entry clones for various reverse proteomics (ORFeome v3.1). This work illustrates why the cloning of a complete C. elegans ORFeome, and likely the ORFeomes of other multicellular organisms, needs to be an iterative process that requires multiple rounds of experimental validation together with gradually improving gene predictions. C1 Harvard Univ, Sch Med, 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. Fac Univ Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Belgium. Agencourt Biosci Corp, Beverly, MA 01915 USA. RP Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Hill, David/B-6617-2011 FU NCI NIH HHS [7 R33 CA81658-02]; NHGRI NIH HHS [5R01HG01715-02, R01 HG001715] NR 18 TC 67 Z9 73 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2064 EP 2069 DI 10.1101/gr.2496804 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000010 PM 15489327 ER PT J AU Hope, IA Stevens, J Garner, A Hayes, J Cheo, DL Brasch, MA Vidal, M AF Hope, IA Stevens, J Garner, A Hayes, J Cheo, DL Brasch, MA Vidal, M TI Feasibility of genome-scale construction of promoter :: reporter gene fusions for expression in Caenorhabditis elegans using a MultiSite Gateway recombination system SO GENOME RESEARCH LA English DT Article ID C-ELEGANS; DNA AB The understanding of gene function increasingly requires the characterization of DNA segments containing promoters and their associated regulatory sequences. We describe a novel approach for linking multiple DNA segments, here applied to the generation of promoter:: reporter fusions. Promoters from Caenorhabditis elegans genes were cloned using the MultiSite Gateway cloning technology. The capacity for using this system for efficient construction of chimeric genes was explored by constructing promoter:: reporter gene fusions with a gfp reporter. The promoters were found to provide appropriate expression of GFP upon introduction into C. elegans, demonstrating that the short Gateway recombination site between the promoter and the reporter did not interfere with transcription or translation. The recombinational cloning involved in the Gateway system, which permits the highly efficient and precise transfer of DNA segments between plasmid vectors, makes this technology ideal for genomics research programs. C1 Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. Invitrogen Corp, Carlsbad, CA 92008 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. EM i.a.hope@leeds.ac.uk FU NCI NIH HHS [R21 CA097516] NR 16 TC 28 Z9 31 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2070 EP 2075 DI 10.1101/gr.2463804 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000011 PM 15489328 ER PT J AU Deplancke, B Dupuy, D Vidal, M Walhout, AJM AF Deplancke, B Dupuy, D Vidal, M Walhout, AJM TI A gateway-compatible yeast one-hybrid system SO GENOME RESEARCH LA English DT Article ID C-ELEGANS; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; HOMEODOMAIN PROTEIN; MUSCLE DEVELOPMENT; TARGET GENES; GENOME; DNA; DATABASE AB Since the advent of microarrays, vast amounts of gene expression data have been generated. However, these, microarray data fail to reveal the transcription regulatory mechanisms that underlie differential gene expression, because the identity of the responsible transcription factors (TFs) often cannot be directly inferred from such data sets. Regulatory TFs activate or repress transcription of their target genes by binding to cis-regulatory elements that are frequently located in a gene's promoter. To understand the mechanisms underlying differential gene expressior, it is necessary to identify physical interactions between regulatory TFs and their target genes. We developed 3 Gateway-compatible yeast one-hybrid (Y1H) system that enables the rapid, large-scale identification of protein-DNA interactions using both small (i.e., DNA elements of interest) and large (i.e., gene promoters) DNA fragments. We used four well-characterized Caenorhabditis elegans promoters as DNA baits to test the functionality of this Y1H system. We could detect similar to40% of previously reported TF-promoter interactions. By performing screens using two complementary libraries, we found novel potentially interacting TFs for each promoter. We recapitulated several of the Y1H-based protein-DNA interactions using liciferase reporter assays in mammalian cells. Taken together, the Gateway-compatible Y1H system will allow the high-throughput identification of protein-DNA interactions and may be a valuable tool to decipher transcription regulatory networks. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, 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, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. EM marian.walhout@umassmed.edu RI Deplancke, Bart/B-3250-2008; Dupuy, Denis/M-7299-2014; OI Deplancke, Bart/0000-0001-9935-843X; Walhout, Marian/0000-0001-5587-3608; Dupuy, Denis/0000-0002-4781-5595 FU NCI NIH HHS [4 R33 CA097516-02, R33 CA097516] NR 55 TC 114 Z9 119 U1 1 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2093 EP 2101 DI 10.1101/gr.2445504 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000014 PM 15489331 ER PT J AU Luan, CH Qiu, SH Finley, JB Carson, M Gray, RJ Huang, WY Johnson, D Tsao, J Reboul, J Vaglio, P Hill, DE Vidal, M Delucas, LJ Luo, M AF Luan, CH Qiu, SH Finley, JB Carson, M Gray, RJ Huang, WY Johnson, D Tsao, J Reboul, J Vaglio, P Hill, DE Vidal, M Delucas, LJ Luo, M TI High-throughput expression of C-elegans proteins SO GENOME RESEARCH LA English DT Article ID STRUCTURAL GENOMICS; CAENORHABDITIS-ELEGANS; PROTEOMICS; PIPELINE; CLONING AB Proteome-scale studies of protein three-dimensional structures should provide valuable information for both investigating basic biology and developing therapeutics. Critical for these endeavors is the expression of recombinant proteins. We selected Caenorhabditis elegans as our model organism in a structural proteomics initiative because of the high quality of its genome sequence and the availability of its ORFeome, protein-encoding open reading frames (ORFs), in a flexible recombinational cloning format. We developed a robotic pipeline for recombinant protein expression, applying the Gateway cloning/expression technology and utilizing a stepwise automation strategy on an integrated robotic platform. Using the pipeline, we have carried out heterologous protein expression experiments on 10,167 ORFs of C. elegans. With one expression vector and one Escherichia coli strain, protein expression was observed for 4854 ORFs, and 1536 were soluble. Bioinformatics analysis of the data indicates that protein hydrophobicity is a key determining factor for an ORF to yield a soluble expression product. This protein expression effort has investigated the largest number of genes in any organism to date. The pipeline described here is applicable to high-throughput expression of recombinant proteins for other species, both prokaryotic and eukaryotic, provided that ORFeome resources become available. C1 Univ Alabama Birmingham, Ctr Biophys Sci & Engn, SE Collaboratory Struct Genom, Birmingham, AL 35294 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. RP Univ Alabama Birmingham, Ctr Biophys Sci & Engn, SE Collaboratory Struct Genom, Birmingham, AL 35294 USA. EM Iuanch@uab.edu; mingluo@uab.edu RI Hill, David/B-6617-2011; Reboul, Jerome/P-9103-2016 OI Reboul, Jerome/0000-0002-5513-4546 FU NIGMS NIH HHS [1P50-GM62407, P50 GM062407] NR 29 TC 73 Z9 80 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2102 EP 2110 DI 10.1101/gr.2520504 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000015 PM 15489332 ER PT J AU Rual, JF Hirozane-Kishikawa, T Hao, T Bertin, N Li, SM Dricot, A Li, N Rosenberg, J Lamesch, P Vidalain, PO Clingingsmith, TR Hartley, JL Esposito, D Cheo, D Moore, T Simmons, B Sequerra, R Bosak, S Doucette-Stamm, L Le Peuch, C Vandenhaute, J Cusick, ME Albala, JS Hill, DE Vidal, M AF Rual, JF Hirozane-Kishikawa, T Hao, T Bertin, N Li, SM Dricot, A Li, N Rosenberg, J Lamesch, P Vidalain, PO Clingingsmith, TR Hartley, JL Esposito, D Cheo, D Moore, T Simmons, B Sequerra, R Bosak, S Doucette-Stamm, L Le Peuch, C Vandenhaute, J Cusick, ME Albala, JS Hill, DE Vidal, M TI Human ORFeome version 1.1: A platform for reverse proteomics SO GENOME RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; CAENORHABDITIS-ELEGANS; PROTEIN COMPLEXES; SYSTEMS BIOLOGY; GENOME SEQUENCE; GENES; PROJECTS; DATABASE; GATEWAY; CLONING AB The advent of systems biology necessitates the cloning of nearly entire sets of protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional studies of the corresponding proteomes. Here, we describe the generation of a first version of the human ORFeome using a newly improved Gateway recombinational cloning approach. Using the Mammalian Gene Collection (MGC) resource as a starting point, we report the successful cloning of 8076 human ORFs, representing at least 7263 human genes, as mini-pools of PCR-amplified products. These were assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After assessing the overall quality of this version, we describe the use of hORFeome v1.1 for heterologous protein expression in two different expression systems at proteome scale. The hORFeome v1.1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome. C1 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. Fac Univ Notre Dame Paix, B-5000 Namur, Belgium. CNRS, FRE 2593, Ctr Rech Biochim Macromol, F-34293 Montpellier 5, France. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. Atto Biosci, Rockville, MD 20850 USA. Open Biosyst Inc, Huntsville, AL 35806 USA. Agencourt Biosci Corp, Beverly, MA 01905 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM david_hill@dfci.harvard.edu; marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Hill, David/B-6617-2011 OI Bertin, Nicolas/0000-0002-9835-9606; FU NCI NIH HHS [U01 CA105423, U01 CA105423-01] NR 39 TC 135 Z9 142 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2128 EP 2135 DI 10.1101/gr.2973604 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000018 PM 15489335 ER PT J AU Rual, JF Ceron, J Koreth, J Hao, T Nicot, AS Hirozane-Kishikawa, T Vandenhaute, J Orkin, SH Hill, DE van den Heuvel, S Vidal, M AF Rual, JF Ceron, J Koreth, J Hao, T Nicot, AS Hirozane-Kishikawa, T Vandenhaute, J Orkin, SH Hill, DE van den Heuvel, S Vidal, M TI Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library SO GENOME RESEARCH LA English DT Article ID GENOME-WIDE RNAI; DOUBLE-STRANDED-RNA; C-ELEGANS; GENETIC INTERFERENCE; CHROMOSOME-I; PROJECTS; DNA; CONSTRUCTION; PHENOTYPES; RESOURCE AB The recently completed Caenorhabditis elegans genome sequence allows application of high-throughput (HT) approaches for phenotypic analyses using RNA interference (RNAi). As large phenotypic data sets become available, "phenoclustering" strategies can be used to begin understanding the complex molecular networks involved in development and other biological processes. The Current HT-RNAi resources represent a great asset for phenotypic profiling but are limited by lack of flexibility. For instance, existing resources do not take advantage of the latest improvements in RNAi technology, such as inducible hairpin RNAi. Here we show that a C. elegans ORFeome resource, generated with the Gateway cloning system, can be used as a starting point to generate alternative HT-RNAi resources with enhanced flexibility. The versatility inherent to the Gateway system suggests that additional HT-RNAi libraries can now be readily generated to perform gene knockdowns under various conditions, increasing the possibilities for phenome mapping in C, elegans. C1 Harvard Univ, Sch Med, Gen Hosp Canc Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Fac Univ Notre Dame Paix, B-5000 Namur, Belgium. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Gen Hosp Canc Ctr, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu; marc_vidal@dfci.harvard.edu RI van den Heuvel, Sander/B-8892-2011; Hill, David/B-6617-2011; OI Rual, Jean-Francois/0000-0003-4465-8819 FU NCI NIH HHS [7 R33 CA81658-02, CA95281, P01 CA095281] NR 41 TC 399 Z9 406 U1 1 U2 17 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2162 EP 2168 DI 10.1101/gr.2505604 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000022 PM 15489339 ER PT J AU Dupuy, D Li, QR Deplancke, B Boxem, M Hao, T Lamesch, P Sequerra, R Bosak, S Doucette-Stamm, L Hope, IA Hill, DE Walhout, AJM Vidal, M AF Dupuy, D Li, QR Deplancke, B Boxem, M Hao, T Lamesch, P Sequerra, R Bosak, S Doucette-Stamm, L Hope, IA Hill, DE Walhout, AJM Vidal, M TI A first version of the Caenorhabditis elegans promoterome SO GENOME RESEARCH LA English DT Article ID FUNCTIONAL GENOMIC ANALYSIS; C-ELEGANS; GENE-EXPRESSION; GLOBAL ANALYSIS; RNAI ANALYSIS; PROTEIN; BIOLOGY; MAP; TRANSFORMATION; LOCALIZATION AB An important aspect of the development of systems biology approaches in metazoans is the characterization of expression patterns of nearly all genes predicted from genome sequences. Such "localizome" maps should provide information on where (in what cells or tissues) and when (at what stage of development or under what conditions) genes are expressed. They should also indicate in what cellular compartments the corresponding proteins are localized. Caenorhabditis elegans is particularly suited for the development of a localizome neap since all its 959 adults: somatic cells can be visualized by microscopy, and its cell lineage has been completely described. Here we address one of the challenges of C. elegans localizome mapping projects: that of obtaining a genome-wide resource of C, elegans promoters needed to generate transgenic animals expressing localization markers such as the green fluorescent protein (GFP). To ensure high flexibility for future uses, we utilized the newly developed Multisite Gateway system. We generated and validated "version 1.1" of the Promoterome: a resource of similar to6000 C elegans promoters. These promoters can be transferred easily into various Gateway Destination vectors to drive expression of markers such as GFP, alone (promoter::GFP constructs), or in fusion with protein-encoding open reading frames available in ORFeome resources (promoter:: ORF::GFP). C1 Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. Agencourt Biosci Corp, Beverly, MA 01915 USA. RP Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Deplancke, Bart/B-3250-2008; Boxem, Mike/B-8857-2011; Hill, David/B-6617-2011; Dupuy, Denis/M-7299-2014; OI Boxem, Mike/0000-0003-3966-4173; Deplancke, Bart/0000-0001-9935-843X; Walhout, Marian/0000-0001-5587-3608; Dupuy, Denis/0000-0002-4781-5595 FU NCI NIH HHS [4 R33 CA097516-02, R33 CA097516] NR 47 TC 101 Z9 104 U1 2 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2169 EP 2175 DI 10.1101/gr.2497604 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000023 PM 15489340 ER PT J AU Dricot, A Rual, JF Lamesch, P Bertin, N Dupuy, D Hao, T Lambert, C Hallez, R Delroisse, JM Vandenhaute, J Lopez-Goni, I Moriyon, I Garcia-Lobo, JM Sangari, FJ MacMillan, AP Cutler, SJ Whatmore, AM Bozak, S Sequerra, R Doucette-Stamm, L Vidal, M Hill, DE Letesson, JJ De Bolle, X AF Dricot, A Rual, JF Lamesch, P Bertin, N Dupuy, D Hao, T Lambert, C Hallez, R Delroisse, JM Vandenhaute, J Lopez-Goni, I Moriyon, I Garcia-Lobo, JM Sangari, FJ MacMillan, AP Cutler, SJ Whatmore, AM Bozak, S Sequerra, R Doucette-Stamm, L Vidal, M Hill, DE Letesson, JJ De Bolle, X TI Generation of the Brucella melitensis ORFeome version 1.1 SO GENOME RESEARCH LA English DT Article ID OPEN READING FRAMES; INTRACELLULAR TRAFFICKING; PROTEIN EXPRESSION; BIOLOGICAL WARFARE; PLANT-PATHOGENS; HELA-CELLS; NASTY BUG; VIRULENCE; CLONING; SUIS AB The bacteria of the Brucella genus are responsible for a worldwide zoonosis called brucellosis. They belong to the alpha-proteobacteria group, as many other bacteria that live in close association with a eukaryotic host. Importantly, the Brucellae are mainly intracellular pathogens, and the molecular mechanisms of their virulence are still poorly understood. Using the complete genome sequence of Brucella melitensis, we generated a database of protein-coding open reading frames (ORFs) and constructed an ORFeome library of 3()91 Gateway Entry clones, each containing,3 defined ORF. This first version of the Brucella ORFeome (v1.1) provides the coding sequences in a user-friendly format amenable to high-throughput functional genomic and proteomic experiments, as the ORFs are conveniently transferable from the Entry clones to various Expression vectors by recombinational cloning. The cloning of the Brucella ORFeome v1.1 should help to provide a better understanding of the molecular mechanisms of virulence, including the identification of bacterial protein-protein interactions, but also interactions between bacterial effectors and their host's targets. C1 Univ Namur, Res Unit Mol Biol, B-5000 Namur, Belgium. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Navarra, Dept Microbiol, Pamplona 31008, Spain. Univ Cantabria, Dept Biol Mol, Santander 39011, Spain. WHO, FAO, Collaborating Ctr Reference & Res Brucellosis, Dept Statutory & Exot Bacterial Dis, Weybridge KT15 3NB, Surrey, England. Agencourt Biosci Corp, Beverly, MA 01915 USA. RP De Bolle, X (reprint author), Univ Namur, Res Unit Mol Biol, B-5000 Namur, Belgium. EM xavier.debolle@fundp.ac.be RI Bertin, Nicolas/C-3025-2008; Whatmore, Adrian/C-7744-2011; Hill, David/B-6617-2011; Garcia Lobo, Juan/K-2727-2014; Dupuy, Denis/M-7299-2014; Moriyon, Ignacio/N-4764-2016; OI Bertin, Nicolas/0000-0002-9835-9606; Garcia Lobo, Juan/0000-0002-9187-0671; Moriyon, Ignacio/0000-0002-4288-0195; Lopez-Goni, Ignacio/0000-0002-3873-8743; Hallez, Regis/0000-0003-1175-8565 NR 40 TC 58 Z9 60 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2004 VL 14 IS 10B BP 2201 EP 2206 DI 10.1101/gr.2456204 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 862TM UT WOS:000224514000026 PM 15489343 ER PT J AU Hao, K Li, C Rosenow, C Wong, WH AF Hao, K Li, C Rosenow, C Wong, WH TI Estimation of genotype error rate using samples with pedigree information - an application on the GeneChip Mapping 10K array SO GENOMICS LA English DT Article DE genotyping error; Mendelian inheritance; GeneChip Mapping 10K array; single nucleotide polymorphism ID SINGLE NUCLEOTIDE POLYMORPHISMS; TRANSMISSION/DISEQUILIBRIUM TEST; GENETIC ASSOCIATION; POWER AB Currently, most analytical methods assume all observed genotypes are correct; however, it is clear that errors may reduce statistical power or bias inference in genetic studies. We propose procedures for estimating error rate in genetic analysis and apply them to study the GeneChip Mapping 10K array, which is a technology that has recently become available and allows researchers to survey over 10,000 SNPs in a single assay. We employed a strategy to estimate the genotype error rate in pedigree data. First, the "dose -response" reference curve between error rate and the observable error number were derived by simulation, conditional on given pedigree structures and genotypes. Second, the error rate was estimated by calibrating the number of observed errors in real data to the reference curve. We evaluated the performance of this method by simulation study and applied it to a data set of 30 pedigrees genotyped using the GeneChip Mapping 10K array. This method performed favorably in all scenarios we surveyed. The dose-response reference curve was monotone and almost linear with a large slope. The method was able to estimate accurately the error rate under various pedigree structures and error models and under heterogeneous error rates. Using this method, we found that the average genotyping error rate of the GeneChip Mapping I OK array was about 0.1%. Our method provides a quick and unbiased solution to address the genotype error rate in pedigree data. It behaves well in a wide range of settings and can be easily applied in other genetic projects. The robust estimation of genotyping error rate allows us to estimate power and sample size and conduct unbiased genetic tests. The GeneChip Mapping I OK array has a low overall error rate, which is consistent with the results obtained from alternative genotyping assays. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. Genom Collaborat, Santa Clara, CA USA. Harvard Univ, Dept Stat, Sch Med, Cambridge, MA USA. RP Wong, WH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM wwong@hsph.harvard.edu FU NHGRI NIH HHS [1R01HG02341] NR 23 TC 26 Z9 26 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 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2004 VL 84 IS 4 BP 623 EP 630 DI 10.1016/j.ygeno.2004.05.003 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 857BU UT WOS:000224091200001 PM 15475239 ER PT J AU Mader, S Reed, J Schutzer, W AF Mader, S Reed, J Schutzer, W TI Interaction between G protein receptor kinase-2 and caveolin decline with age in Fischer 344 vascular smooth muscle SO GERONTOLOGIST LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 9 EP 9 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800027 ER PT J AU Rafi, A Makinodan, T Uyemura, K Castle, S AF Rafi, A Makinodan, T Uyemura, K Castle, S TI Modulation of the immune response by histamine in adults versus elders SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 10 EP 11 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800032 ER PT J AU Huang, X White, A Wang, X AF Huang, X White, A Wang, X TI Homocysteine and Alzheimer's amyloid pathology SO GERONTOLOGIST LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Univ Melbourne, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 26 EP 26 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800084 ER PT J AU Shores, M Platas, A Legner, V Kivlahan, D Li, E Matsumoto, A Sadak, T AF Shores, M Platas, A Legner, V Kivlahan, D Li, E Matsumoto, A Sadak, T TI The effect of testosterone on depressive symptoms and function in hypogonadal men with subsyndromal depression SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 33 EP 33 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800106 ER PT J AU Webber, A Martin, J Alessi, C Josephson, K Harker, J AF Webber, A Martin, J Alessi, C Josephson, K Harker, J TI Nighttime noise in the post-acute rehabilitation nursing home setting SO GERONTOLOGIST LA English DT Meeting Abstract C1 Sepulveda GRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 38 EP 38 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800118 ER PT J AU Boyd, C Fortinsky, R Landefeld, C Palmer, R Counsell, S Burant, C Covinsky, K AF Boyd, C Fortinsky, R Landefeld, C Palmer, R Counsell, S Burant, C Covinsky, K TI Functional recovery in activities of daily living (ADLS) among older adults whose ADL function declined during hospitalization for acute illness SO GERONTOLOGIST LA English DT Meeting Abstract C1 Johns Hopkins Univ, Ctr Aging & Hlth, Div Geriatr Med & Gerontol, Baltimore, MD USA. Ctr Aging, Farmington, CT USA. San Francisco VAMC, Div Geriatr, San Francisco, CA USA. Cleveland Clin Fdn, Dept Gen Internal Med, Cleveland, OH USA. Univ Connecticut, Ctr Hlth, Div Geriatr, Ctr Aging, Storrs, CT 06269 USA. Case Western Reserve Univ, Dept Sociol & Bioeth, Cleveland, OH USA. Case Western Reserve Univ, Sch Nursing, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 40 EP 41 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800124 ER PT J AU Webber, A Harker, J Martin, J Alessi, C Josephson, K AF Webber, A Harker, J Martin, J Alessi, C Josephson, K TI Social isolation and rehabilitation outcomes in older people receiving postacute rehabilitation in the nursing home setting SO GERONTOLOGIST LA English DT Meeting Abstract C1 Sepulveda GRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800126 ER PT J AU Ostwald, S Robinson-Whelen, S Swank, P AF Ostwald, S Robinson-Whelen, S Swank, P TI Minority stroke survivors and spousal caregivers: Are poorer outcomes due to ethnicity, SES or age? SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Houston, TX USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 81 EP 81 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800236 ER PT J AU Burant, C Graham, G Ibrahim, S Kwoh, C Siminoff, L AF Burant, C Graham, G Ibrahim, S Kwoh, C Siminoff, L TI Predictors of depression and subjective health in a male VA population treated for osteoarthritis: A structural equation model SO GERONTOLOGIST LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RI Siminoff, Laura /H-6277-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 99 EP 99 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800289 ER PT J AU Moye, J Karlawish, J Wood, S Kim, S Marson, D AF Moye, J Karlawish, J Wood, S Kim, S Marson, D TI Capacity to consent to treatment: Cognitive predictors of capacity in older adults with dementia SO GERONTOLOGIST LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Colorado, Colorado Springs, CO 80933 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Alabama, UAB Stn, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 102 EP 103 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800298 ER PT J AU Karel, M Moye, J Azar, A Bank, A AF Karel, M Moye, J Azar, A Bank, A TI Assessing values for advance care planning in older adults with and without dementia SO GERONTOLOGIST LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brockton, MA USA. VA Boston Healthcare Syst, Brockton, MA USA. Univ Louisville, Louisville, KY 40292 USA. Miami Univ, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 136 EP 136 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800385 ER PT J AU Kimbell, A AF Kimbell, A TI A psychometric study of items predicting decisions on allegations of elder abuse, neglect, and exploitation SO GERONTOLOGIST LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 158 EP 158 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458800452 ER PT J AU Wray, L Fonda, S AF Wray, L Fonda, S TI The utility of the HRS for measuring health and function: The first decade of evidence SO GERONTOLOGIST LA English DT Meeting Abstract C1 Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 239 EP 239 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458801001 ER PT J AU Radcliff, T Duncan, R Dobalian, A AF Radcliff, T Duncan, R Dobalian, A TI Seasonal migration of elders and its impact on hospital financial performance SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Colorado, Denver, CO USA. Denver VAMC, Denver, CO USA. Univ Florida, Gainesville, FL USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 249 EP 249 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458801032 ER PT J AU Jarvik, L Matsuyama, S Rasgon, N Jimenez, E La Rue, A Holt, L Larson, S Steh, B Schaeffer, J Harrison, T Yaralian, P AF Jarvik, L Matsuyama, S Rasgon, N Jimenez, E La Rue, A Holt, L Larson, S Steh, B Schaeffer, J Harrison, T Yaralian, P TI Alzheimer offspring 20-years later - No significant cognitive decline? SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Stanford Sch Med, Palo Alto, CA USA. Huebner & Associates, Richland Ctr, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 259 EP 260 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458801061 ER PT J AU Hightower, A Larson, E Borson, S Asthana, S Boyko, E AF Hightower, A Larson, E Borson, S Asthana, S Boyko, E TI Medication management test performance in cognitively intact community-dwelling elders SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, HSR&D, Ctr Excellence, Seattle, WA USA. Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 308 EP 309 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458801208 ER PT J AU Kramer, B Harker, J Wang, M Finke, B AF Kramer, B Harker, J Wang, M Finke, B TI Dual use of VA and Indian Health Service: A pilot study SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Geriatr Res Educ Clin Ctr, Sepulveda, CA USA. Va Greater Los Angeles Healthcare Syst GRECC, Sepulveda, CA USA. Va Greater Los Angeles Healthcare Syst HSR&D, Sepulveda, CA USA. Indian Hlth Serv, Northampton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 449 EP 449 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802031 ER PT J AU Sherman, A Howe, J Villanti, A Sheehan, C Toner, J Fulmer, T AF Sherman, A Howe, J Villanti, A Sheehan, C Toner, J Fulmer, T TI Emergency preparedness: Geriatric mental health concerns SO GERONTOLOGIST LA English DT Meeting Abstract C1 Consortium New York Geriatr Educ Ctr, New York, NY USA. Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. Columbia Univ, Relig & Earth Inst, Ctr Study Sci, New York, NY USA. Bronx Vet Adm Med Ctr, New York, NY USA. Columbia Univ, Stroud Ctr, New York, NY USA. NYU, Div Nursing, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 501 EP 501 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802191 ER PT J AU Chau, C Zeleznik, J Martino-Starvaggi, F AF Chau, C Zeleznik, J Martino-Starvaggi, F TI Are preprinted hospice orders appropriate for geriatric patients? SO GERONTOLOGIST LA English DT Meeting Abstract C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 503 EP 503 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802196 ER PT J AU Rodrigez, K Young, A Appelt, C AF Rodrigez, K Young, A Appelt, C TI Elderly veterans' decision-making processes regarding life-sustaining treatment SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 524 EP 524 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802256 ER PT J AU Jerskey, B Simpson, J Lyons, M Kirkhart, E Nir, T Tsuang, M AF Jerskey, B Simpson, J Lyons, M Kirkhart, E Nir, T Tsuang, M TI The relationship of combat-related resentment to current well-being in Vietnam veterans SO GERONTOLOGIST LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Brockton, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RI Lyons, Michael/B-6119-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 568 EP 568 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802377 ER PT J AU Nir, T Simpson, J Tsuang, M Jerskey, B Lyons, M AF Nir, T Simpson, J Tsuang, M Jerskey, B Lyons, M TI Perceived injury during military service and quality of life in middle age SO GERONTOLOGIST LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Brockton, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Boston Univ, Boston, MA 02215 USA. RI Lyons, Michael/B-6119-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2004 VL 44 SI 1 BP 568 EP 568 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 875YJ UT WOS:000225458802376 ER PT J AU McCollum, AD Burrell, SC Haddad, RI Norris, CM Tishler, RB Case, MA Posner, MR Van den Abbeele, AD AF McCollum, AD Burrell, SC Haddad, RI Norris, CM Tishler, RB Case, MA Posner, MR Van den Abbeele, AD TI Positron emission tomography with F-18-fluorodeoxyglucose to predict pathologic response after induction chemotherapy and definitive chemoradiotherapy in head and neck cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE head and neck cancer; positron emission tomography; organ-preservation; chemoradiotherapy; residual disease ID SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; RECURRENT HEAD; TUMOR; RADIOTHERAPY; PET; RESECTION; SALVAGE; SURGERY; TRIAL AB Background. Conventional imaging is limited in identifying persistent disease after organ-preserving therapy for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). We studied the accuracy of positron emission tomography (PET) with F-18-fluoro-2-deoxy-D-glucose (FDG-PET) in restaging disease in patients with SCCHN after they had undergone induction chemotherapy (ICT) followed by chemoradiotherapy (CRT). Methods. Forty patients with advanced SCCHN were treated with ICT followed by CRT. FDG-PET imaging was performed to assess for residual cancer at the primary site and in nodal metastases. Two nuclear medicine physicians interpreted PET scans in random sequence. Test characteristics were calculated with pathologic analysis or clinical recurrence as the standard. Results. After induction chemotherapy, PET imaging had a sensitivity of 100% and specificity of 65% for detecting persistent disease at the primary tumor site. After ICT and CRT were completed, the sensitivity and specificity of PET imaging were 67% and 53%, respectively, for detecting occult disease in cervical lymph nodes. Conclusions. FDG-PET imaging showed some correlation with pathologic response after ICT and CRT in patients with advanced SCCHN. The use of FDG-PET warrants further investigation in this setting. (C) 2004 Wiley Periodicals, Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Nucl Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Otolaryngol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP McCollum, AD (reprint author), Baylor Charles A Sammons Canc Ctr, 3535 Worth St,Suite 240, Dallas, TX 75246 USA. EM mccollum@usoncology.com NR 31 TC 56 Z9 56 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2004 VL 26 IS 10 BP 890 EP 896 DI 10.1002/hed.20080 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 858EO UT WOS:000224173400008 PM 15390197 ER PT J AU Vilaichone, RK Mahachai, V Tumwasorn, S Wu, JY Graham, DY Yamaoka, Y AF Vilaichone, RK Mahachai, V Tumwasorn, S Wu, JY Graham, DY Yamaoka, Y TI Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: A cultural cross roads SO HELICOBACTER LA English DT Article DE cagA; genotype; Helicobacter pylori; Thailand; vacA ID CAGA; GENOTYPES; VACA; ASSOCIATION; POPULATIONS; DISEASES; REGION; CANCER AB Background. Thailand is at the cultural cross roads between East and South Asia. It has been suggested that this is also the region where the predominant Helicobacter pylori (H. pylori) genotype changes from East Asian to South Asian. Methods. We compared the molecular epidemiology and outcome of H. pylori infections among different ethnic groups in Thailand (Thai, Thai-Chinese and Chinese). H. pylori isolates were genotyped by polymerase chain reaction based on cagA, cag right end junction and vacA genotypes. Results. Ninety-eight isolates from 38 ethnic Thai, 20 ethnic Chinese and 40 Thai-Chinese were categorized into East Asian (45%), South/Central Asian (26%), Western (1%) or mixed type (29%). The East Asian genotype was the most common among Chinese (85%) and Thai-Chinese (55%) (p < .01 compared to ethnic Thai). The ethnicity of the mother among mixed Thai-Chinese marriages predicted the genotype of the child's H. pylori (e.g. when the mother was Chinese, 84% had East Asian type vs. 29% when the mother was Thai) (p < .001). Gastric cancer was common among ethnic Chinese with East Asian genotype (e.g. all Chinese with gastric cancer or peptic ulcer disease had East Asian genotype, whereas only 40% of Chinese with gastritis had this genotype). Conclusions. Immigration, intermarriage and the variety of H. pylori genotypes in Thailand suggest that Thailand is an ideal site for epidemiological studies attempting to relate H. pylori genotypes and host factors to outcome. Our data also support the hypothesis that the primary caretaker of the children is most likely the source of the infection. C1 Michael E Debakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Thammasat Univ Hosp, Dept Med, Gastroenterol Unit, Pathum Thani, Thailand. Baylor Coll Med, Houston, TX 77030 USA. Chulalongkorn Univ Hosp, Dept Med, Gastroenterol Unit, Bangkok, Thailand. Chulalongkorn Univ Hosp, Dept Microbiol, Bangkok, Thailand. RP Yamaoka, Y (reprint author), Michael E Debakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [DK56,338] NR 17 TC 56 Z9 58 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2004 VL 9 IS 5 BP 453 EP 459 DI 10.1111/j.1083-4389.2004.00260.x PG 7 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 852UE UT WOS:000223781200011 PM 15361085 ER PT J AU Dadras, SS Detmar, M AF Dadras, SS Detmar, M TI Angiogenesis and lymphanglogenesis of skin cancers SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID LYMPH-NODE METASTASIS; GROWTH-FACTOR-C; TUMOR LYMPHANGIOGENESIS; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; PROGNOSTIC VALUE; FACTOR EXPRESSION; VESSEL DENSITY; THIN MELANOMAS; VEGF-C AB Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread by way of lymphatic vessels to regional lymph nodes; lymph node metastasis is a major determinant for the staging and clinical management of melanoma. The importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread is unclear, however. Recent experimental and clinical evidence strongly suggest that active lymphangiogenesis is induced by many tumor types, including cutaneous melanoma, and that it plays an important role in lymphatic tumor dissemination. The extent of tumor-associated lymphangiogenesis can serve as a powerful prognostic tool for the evaluation of primary cutaneous melanomas. A better molecular understanding of the lymphatic system may provide new insights into the biology of tumor metastasis and may provide novel prognostic and therapeutic tools in metastatic disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Detmar, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA86410, CA91861, CA69184] NR 56 TC 24 Z9 28 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2004 VL 18 IS 5 BP 1059 EP + DI 10.1016/j.hoc.2004.06.009 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 866ZA UT WOS:000224810700008 PM 15474335 ER PT J AU Golden-Mason, L Rosen, H O'Farrelly, C AF Golden-Mason, L Rosen, H O'Farrelly, C TI Early changes in CD56+lymphoid populations predict outcome post liver transplantation (LT) for hepatitis C viral infection SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 St Vincents Univ Hosp, Dublin, Ireland. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 163A EP 163A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100006 ER PT J AU Rosen, H Hinrichs, DJ Leistikow, R Callender, G Nishimura, M Lewinsohn, D AF Rosen, H Hinrichs, DJ Leistikow, R Callender, G Nishimura, M Lewinsohn, D TI Selection of HCV-specific CD8+T cells by donor HLA alleles following liver transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, Portland, OR USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 164A EP 164A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100007 ER PT J AU Schiano, TD Gutierrez, JA Walewski, JL Fiel, MI Cheng, B Nelson, C Bodenheimer, H Thung, SN Chung, R Schwartz, ME Branch, AD AF Schiano, TD Gutierrez, JA Walewski, JL Fiel, MI Cheng, B Nelson, C Bodenheimer, H Thung, SN Chung, R Schwartz, ME Branch, AD TI HCV RNA, core antigen, ALT values, and histology after liver transplantation: Two year follow-up of CDLT versus LDLT. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Mt Sinai Sch Med, New York, NY USA. Beth Isreal, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 164A EP 164A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100008 ER PT J AU Kramer, JR Julapalli, V El-Serag, HB DeBakey, ME AF Kramer, JR Julapalli, V El-Serag, HB DeBakey, ME TI Adherence to guidelines for referral to liver transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Michael E deBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 165A EP 165A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100010 ER PT J AU Rosen, HR Weston, SJ Im, K Belle, SH AF Rosen, HR Weston, SJ Im, K Belle, SH CA Virahep-C Grp TI Ethnicity and the cellular immune response in patients with chronic hepatitis C genotype 1 infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 178A EP 178A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100038 ER PT J AU Lin, WY Choe, WH Hiasa, Y Kamegaya, Y Blackard, JT Clair, JBS Schmidt, EV Chung, RT AF Lin, WY Choe, WH Hiasa, Y Kamegaya, Y Blackard, JT Clair, JBS Schmidt, EV Chung, RT TI HCV subverts interferon signaling by inducing selective degradation of STAT1 SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 199A EP 199A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100086 ER PT J AU Flory, KR Sherman, KE Chung, RT Nelson, JA AF Flory, KR Sherman, KE Chung, RT Nelson, JA TI Improved assessment of HCV replicative potential using a binary replication system. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Cincinnati, Cincinnati, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 256A EP 256A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100209 ER PT J AU Wang, CC McBride, L Weston, SJ Steele, M Scott, E Krantz, E Wald, A Thiede, H Rosen, HR AF Wang, CC McBride, L Weston, SJ Steele, M Scott, E Krantz, E Wald, A Thiede, H Rosen, HR TI Frequent iatrogenic and sexual acquisition of acute hepatitis C in a multi-center study. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Washington, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Tennessee, Memphis, TN USA. Publ Hlth Seattle & King Cty, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 270A EP 270A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100243 ER PT J AU Kalkeri, G Almquist, S Bhan, A Reid, L Chung, RT Kwong, AD AF Kalkeri, G Almquist, S Bhan, A Reid, L Chung, RT Kwong, AD TI Expression of HCV protease in the liver of mice results in liver injury which can be inhibited by VX-950, a vertex HCV protease inhibitor SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Vertex Pharmaceut Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 281A EP 281A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100268 ER PT J AU Brau, N Xiao, PY Trikha, A Sulkowski, MS Rigsby, MO Wright, TL Dieterich, DT Aytaman, A Denenburg, I Paronetto, F Brown, ST Bini, EJ AF Brau, N Xiao, PY Trikha, A Sulkowski, MS Rigsby, MO Wright, TL Dieterich, DT Aytaman, A Denenburg, I Paronetto, F Brown, ST Bini, EJ TI Hepatocellular carcinoma in HIV-infected patients and influence of HIV viral load on survival. A multicenter study. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Bronx Vet Adm Med Ctr, New York, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NYU, Downtown Hosp, New York, NY USA. Johns Hopkins Univ, Baltimore, MD USA. VA Connecticut HCS, New Haven, CT USA. Yale Univ, New Haven, CT USA. San Francisco VA Med Ctr, San Francisco, CA USA. UCSF, San Francisco, CA USA. VA New York Harbor HCS, Brooklyn, NY USA. SUNY Downstate Hlth Sci Ctr, Brooklyn, NY USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 308A EP 309A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100337 ER PT J AU Lok, AS Everhart, JE Chung, RT Padmanabhan, L Shiffman, ML Everson, GT Lindsay, KL Bonkovsky, HL di Bisceglie, AM Lee, WM Ghany, MG Morishima, C AF Lok, AS Everhart, JE Chung, RT Padmanabhan, L Shiffman, ML Everson, GT Lindsay, KL Bonkovsky, HL di Bisceglie, AM Lee, WM Ghany, MG Morishima, C CA Halt-C Trial Investigators TI Prevalence of insulin resistance (IR) and impact on treatment in chronic hepatitis C (CHC). SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Colorado, Denver, CO 80202 USA. Univ So Calif, Los Angeles, CA USA. Univ Connecticut, Farmington, CT USA. St Louis Univ, St Louis, MO 63103 USA. Univ Texas SW, Dallas, TX USA. Univ Calif Irvine, Irvine, CA USA. Univ Washington, Seattle, WA 98195 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 314A EP 315A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100352 ER PT J AU Anand, BS Currie, SL Bini, EJ Ho, SB Dieperink, E Shen, H Wright, TL AF Anand, BS Currie, SL Bini, EJ Ho, SB Dieperink, E Shen, H Wright, TL CA VA-HCV-001 Study Grp TI Recent alcohol use but not prior alcohol use influences hepatitis C antiviral treatment adherence and outcomes: Results of a national multicenter study. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Houston VAMC, Houston, TX USA. San Francisco VAMC, San Francisco, CA USA. VA NY Harbor Healthcare Syst, New York, NY USA. Minneapolis VAMC, Minneapolis, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 316A EP 317A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100357 ER PT J AU Rousseau, CM Ioannou, GN Todd-Stenberg, JA Sloan, KL Dominitz, JA AF Rousseau, CM Ioannou, GN Todd-Stenberg, JA Sloan, KL Dominitz, JA TI The association of race and treatment for hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 339A EP 339A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100405 ER PT J AU Reddy, KR Govindarajan, S Hadziyannis, SJ Marcellin, P Bernstein, D Dienstag, J Bodenheimer, H Rakela, J Messinger, D Ackrill, A AF Reddy, KR Govindarajan, S Hadziyannis, SJ Marcellin, P Bernstein, D Dienstag, J Bodenheimer, H Rakela, J Messinger, D Ackrill, A TI Hepatic steatosis in chronic hepatitis C: Baseline host and viral characteristics, influence on and response to therapy with peginterferon alfa-2a (40 KD) and ribavirin. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Rancho Los Amigos Med Ctr, Downey, CA USA. Henry Dunant Hosp, Athens, Greece. Hop Beaujon, Clichy, France. N Shore Univ Hosp, Manhasset, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Mayo Clin Hosp, Phoenix, AZ USA. IST GmbH, Mannheim, Germany. Roche, Welwyn Garden City, Herts, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 392A EP 392A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100528 ER PT J AU Delgado-Borrego, A Kamegaya, Y Jordan, SH Hiasa, Y Altman, R Chung, RT AF Delgado-Borrego, A Kamegaya, Y Jordan, SH Hiasa, Y Altman, R Chung, RT TI HCV synergizes with body weight in the promotion of insulin resistance in a transgenic mouse model SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 405A EP 405A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100556 ER PT J AU Blackard, JT Smeaton, L Hiasa, Y Horiike, N Onji, M Rodriguez, I Mayer, KH Chung, RT AF Blackard, JT Smeaton, L Hiasa, Y Horiike, N Onji, M Rodriguez, I Mayer, KH Chung, RT TI Detection of hepatitis C virus (HCV) in serum and peripheral blood compartments of HIV-/HCV+ and HIV+/HCV+ women SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ehime Univ, Sch Med, Matsuyama, Ehime 790, Japan. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 409A EP 409A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100565 ER PT J AU Huckans, MS Blackwell, AD Harms, TA Indest, DW Hauser, P AF Huckans, MS Blackwell, AD Harms, TA Indest, DW Hauser, P TI Hepatitis C and human immunodeficiency virus: Co-infection rates and co-testing patterns among veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, Portland, OR USA. RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 412A EP 413A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100573 ER PT J AU Iken, K Bekele, H Koziel, MJ AF Iken, K Bekele, H Koziel, MJ TI Expression of hepatitis C virus (HCV) proteins in hepatocytes increase apoptosis of activated CD4+ and CD8+ T cells. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 BIDMC, Boston, MA USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 439A EP 439A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100636 ER PT J AU Hiasa, Y Blackard, J Tokumoto, Y Horiike, N Michitaka, K Kamegaya, Y Schmidt, EV Chung, RT Onji, M AF Hiasa, Y Blackard, J Tokumoto, Y Horiike, N Michitaka, K Kamegaya, Y Schmidt, EV Chung, RT Onji, M TI Interferon and ribavirin each stimulate hepatocyte interleukin-8 gene expression in a cell-based HCV replication model. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Ehime Univ, Sch Med, Matsuyama, Ehime 790, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 444A EP 444A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100647 ER PT J AU Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, JT Lin, WY Choe, WH Schmidt, EV Chung, RT AF Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, JT Lin, WY Choe, WH Schmidt, EV Chung, RT TI HCV envelope glycoproteins suppress apoptosis in a transgenic mouse model of HCC: Mechanistic confirmation from hepatocyte-derived cell lines. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis 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 JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100649 ER PT J AU Timm, J Lauer, G Kavanagh, D Kim, A Ouchi, K Reyor, L Lucas, M Gandhi, R Klenerman, P Walker, B Allen, T AF Timm, J Lauer, G Kavanagh, D Kim, A Ouchi, K Reyor, L Lucas, M Gandhi, R Klenerman, P Walker, B Allen, T TI CTL epitope escape and reversion in acute HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Oxford, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 449A EP 449A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100660 ER PT J AU Shinoda, M Tilles, A Wakabayashi, G Takayanagi, A Berthiaume, F Shimazu, M Shimizu, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML AF Shinoda, M Tilles, A Wakabayashi, G Takayanagi, A Berthiaume, F Shimazu, M Shimizu, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML TI Treatment of fulminant hepatic failure in rats with interleukin-1 receptor antagonist producing porcine hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Keio Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 504A EP 504A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100782 ER PT J AU McGuire, BM Bonkovsky, HL Carithers, RL Chung, RT Goldstein, LI Lake, JR Lok, AS Potter, CJ Rand, E Voigt, MD Bloomer, JR AF McGuire, BM Bonkovsky, HL Carithers, RL Chung, RT Goldstein, LI Lake, JR Lok, AS Potter, CJ Rand, E Voigt, MD Bloomer, JR TI Liver transplantation for erythropoietic protoporphyria. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Alabama, Birmingham, AL USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Ohio State Univ, Columbus, OH 43210 USA. Columbus Childrens Hosp, Columbus, OH USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Iowa, Iowa City, IA USA. RI Lok, Anna /B-8292-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 551A EP 551A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100896 ER PT J AU Stanger, B Melton, D AF Stanger, B Melton, D TI Regulation of bile duct development by Notch signals. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 615A EP 615A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102101051 ER PT J AU Parola, M Aleffi, S Petrai, I Aragno, M Mastrocola, R Novo, E Zamara, E Delogu, W Defranco, R Pinzani, M Rollins, BJ Marra, F AF Parola, M Aleffi, S Petrai, I Aragno, M Mastrocola, R Novo, E Zamara, E Delogu, W Defranco, R Pinzani, M Rollins, BJ Marra, F TI Reduced liver injury is associated with diminished oxidative stress in monocyte chemoattractant protein-1 (MCP-1) - Deficient mice SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Turin, Turin, Italy. Univ Florence, Florence, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 704A EP 705A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102101244 ER PT J AU Ahmad, J Cacciarelli, T AF Ahmad, J Cacciarelli, T TI Disparity in the MELD scores of liver transplant recipients in the US according to the size of transplant center. SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 718A EP 718A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102101275 ER PT J AU Afdhal, N Godofsky, E Dienstag, J Rustgi, V Schick, L McEniry, D Zhou, XJ Chao, G Fang, C Fielman, B Myers, M Brown, N AF Afdhal, N Godofsky, E Dienstag, J Rustgi, V Schick, L McEniry, D Zhou, XJ Chao, G Fang, C Fielman, B Myers, M Brown, N TI Final phase I/II trial results for NM283, a new polymerase inhibitor for hepatitis C: Antiviral efficacy and tolerance in patients with HCV-1 infection, including previous interferon failures SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Bach & Godofsky, Bradenton, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Metropolitan Res, Fairfax, VA USA. Univ Massachusetts, Ctr Hlth, Worcester, MA 01605 USA. NW Med Specialties PLLC, Tacoma, WA USA. Idenix Pharmaceut, Cambridge, MA USA. NR 0 TC 19 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 726A EP 726A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102101292 ER PT J AU Piasecki, BA Lewis, JD Reddy, KR Bellamy, SL Porter, SB Weinrieb, RM Stieritz, DD Chang, KM AF Piasecki, BA Lewis, JD Reddy, KR Bellamy, SL Porter, SB Weinrieb, RM Stieritz, DD Chang, KM TI Influence of alcohol use, race, and viral coinfections on spontaneous HCV clearance in a US veteran population SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; CELLULAR IMMUNE-RESPONSE; LIVER-DISEASE; NATURAL-HISTORY; INTERFERON THERAPY; AFRICAN-AMERICANS; UNITED-STATES; B-VIRUS; INFECTION; PREVALENCE AB Hepatitis C virus (HCV) is spontaneously cleared in 15% to 45% of individuals during primary infection. To define the role of alcohol, race, and HBV or HIV coinfections in natural HCV clearance, we examined these parameters in 203 spontaneously HCV-recovered subjects (HCV Ab(+)/RNA(-) subjects without prior antiviral therapy) and 293 chronically HCV-infected patients (HCV Ab(+)/RNA(+)). Subjects were identified from 1,454 HCV antibody-seropositive US veterans tested for HCV RNA between January 2000 and July 2002 at the Philadelphia Veterans Affairs Medical Center. In univariate analysis, alcohol use disorder (odds ratio [OR] 0.52; 95% CI, 0.31-0.85; P=.006) and black race (OR 0.65; 95% CI, 0.44-0.96; P=.024) were both associated with decreased likelihood of spontaneous HCV clearance. In multivariate analyses adjusting for race, HIV infection, age, and alcohol use disorder, alcohol remained strongly associated with reduced HCV clearance (OR 0.49; 95% CI, 0.30-0.8 1; P=.005). In contrast, the association between black race and viral clearance was no longer statistically significant (adjusted OR 0.72; 95% CI, 0.48-1.09; P=.125). HIV coinfection was negatively associated with HCV clearance (OR 0.37; 95% CI, 0.16-0.83; P=.016), while HBV coinfection was positively associated with HCV clearance (unadjusted OR 5.0; 95% CI, 1.26-28.6; P=.008). In conclusion, the likelihood of spontaneous clearance of HCV may be influenced by alcohol and viral coinfections. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Piasecki, BA (reprint author), Radnor Gastroenterol Clin, Penn Med, 250 King Prussia Rd, Radnor, PA 19087 USA. EM Barbara_piasecki@yahoo.com FU NIAAA NIH HHS [AA12849]; NIAID NIH HHS [AI47519]; NIDDK NIH HHS [T32 DK007740] NR 45 TC 49 Z9 52 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 BP 892 EP 899 DI 10.1002/hep.20384 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857AX UT WOS:000224088800016 PM 15382122 ER PT J AU King, GL Loeken, MR AF King, GL Loeken, MR TI Hyperglycemia-induced oxidative stress in diabetic complications SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Review DE oxidative stress; free radicals; diabetic complications ID PROTEIN-KINASE-C; NEURAL-TUBE DEFECTS; INDUCED INSULIN-RESISTANCE; RAT EMBRYO CULTURE; RETINAL BLOOD-FLOW; 3 MAJOR PATHWAYS; VITAMIN-E; GENE-EXPRESSION; HIGH GLUCOSE; LIPOIC ACID AB Reactive oxygen species are increased by hyperglycemia. Hyperglycemia, which occurs during diabetes (both type 1 and type 2) and, to a lesser extent, during insulin resistance, causes oxidative stress. Free fatty acids, which may be elevated during inadequate glycemic control, may also be contributory. In this review, we will discuss the role of oxidative stress in diabetic complications. Oxidative stress may be important in diabetes, not just because of its role in the development of complications, but because persistent hyperglycemia, secondary to insulin resistance, may induce oxidative stress and contribute to beta cell destruction in type 2 diabetes. The focus of this review will be on the role of oxidative stress in the etiology of diabetic complications. C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NEI NIH HHS [EY5110]; NIDDK NIH HHS [DK53105, DK58300] NR 71 TC 200 Z9 210 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD OCT PY 2004 VL 122 IS 4 BP 333 EP 338 DI 10.1007/s00418-004-0678-9 PG 6 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 866DG UT WOS:000224753400006 PM 15257460 ER PT J AU Doherty, CP West, WC Dilley, LC Shattuck-Hufnagel, S Caplan, D AF Doherty, CP West, WC Dilley, LC Shattuck-Hufnagel, S Caplan, D TI Question/statement judgments: An fMRI study of intonation processing SO HUMAN BRAIN MAPPING LA English DT Article DE intonation; fMRI; question; linguistic prosody ID HUMAN AUDITORY-CORTEX; MEDIAL TEMPORAL-LOBE; POSITRON-EMISSION-TOMOGRAPHY; LEFT PREFRONTAL CORTEX; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; EVENT-RELATED FMRI; RIGHT-HEMISPHERE; EMOTIONAL PROSODY; CORTICAL SURFACE AB We examined changes in fMRI BOLD signal associated with question/statement judgments in an event-related paradigm to investigate the neural basis of processing one aspect of intonation. Subjects made judgments about digitized recordings of three types of utterances: questions with rising intonation (RQ; e.g., "She was talking to her father?"), statements with a falling intonation (FS; e.g., "She was talking to her father."), and questions with a falling intonation and a word order change (FQ; e.g., "Was she talking to her father?"). Functional echo planar imaging (EPI) scans were collected from 11 normal subjects. There was increased BOLD activity in bilateral inferior frontal and temporal regions for RQ over either FQ or FS stimuli. The study provides data relevant to the location of regions responsive to intonationally marked illocutionary differences between questions and statements. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA USA. Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA USA. MIT, Speech Commun Grp, Cambridge, MA USA. RP Doherty, CP (reprint author), Royal Coll Surgeons Ireland, Beaumont Hosp, Dublin 9, Ireland. EM cpdoherty@partners.org FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [DC02146] NR 88 TC 28 Z9 28 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2004 VL 23 IS 2 BP 85 EP 98 DI 10.1002/hbm.20042 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 859IL UT WOS:000224256500002 PM 15340931 ER PT J AU Ma, XW Bacci, S Mlynarski, W Gottardo, L Soccio, T Menzaghi, C Iori, E Lager, RA Shroff, AR Gervino, EV Nesto, RW Johnstone, MT Abumrad, NA Avogaro, A Trischitta, V Doria, A AF Ma, XW Bacci, S Mlynarski, W Gottardo, L Soccio, T Menzaghi, C Iori, E Lager, RA Shroff, AR Gervino, EV Nesto, RW Johnstone, MT Abumrad, NA Avogaro, A Trischitta, V Doria, A TI A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians SO HUMAN MOLECULAR GENETICS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; INSULIN-RESISTANCE; GENETIC ASSOCIATION; HYPERTENSIVE-RATS; DEFICIENCY; RECEPTOR; DISEASE; DIFFERENTIATION; METABOLISM; IDENTIFICATION AB CD36 is a class B scavenger receptor recognizing a variety of ligands including long-chain fatty acids and modified LDL. We investigated whether genetic variability at this locus is a determinant of free fatty acid (FFA) plasma levels and risk of coronary artery disease (CAD) in Caucasians. Typing of 21 polymorphic markers, evenly spanning the CD36 gene, revealed two linkage disequilibrium (LD) blocks that could be tagged by five polymorphisms (-33137A>G, -31118G>A, 25444G>A, 27645del>ins and 30294G>C). In 585 non-diabetic individuals of Caucasian origin, the 30294G>C polymorphism was significantly associated with FFA levels (P=0.02)-an effect that was especially visible among men (P=0.009). A similar association was observed in this gender at -33137 (P=0.008) and -31118 (P=0.028). When the five tag polymorphisms were considered together, men carrying the AGGIG haplotype had 31% higher FFA (P=0.0002) and 20% higher triglycerides (P=0.025) than non-carriers. The same haplotype was associated with increased risk of CAD in 197 type 2 diabetic individuals from the US (OR=2.3, 95% CI 1.2-4.2). A similar tendency was observed in a group of 321 type 2 diabetic individuals from Italy (OR=1.4, 0.9-2.3), resulting in an overall relative risk of 1.6 (1.1-2.3, P=0.015) in the two populations considered together. By targeted resequencing, we identified a common variant in the CD36 promoter that is in strong LD with the AGGIG haplotype and could be partly responsible for these findings. In conclusion, this comprehensive study of CD36 variability indicates that the common polymorphisms at this locus modulate lipid metabolism and cardiovascular risk in Caucasians. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Sci Inst Casa Sollievo Sofferenza San Giovanni Ro, Endocrine Unit, San Giovanni Rotondo, Italy. Univ Padua, Dept Clin & Expt Med, Padua, Italy. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Lahey Clin Fdn, Heart & Vasc Ctr, Burlington, MA USA. SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY 11794 USA. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Ctr,1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Trischitta, Vincenzo/K-1487-2016; OI Trischitta, Vincenzo/0000-0003-1174-127X; Menzaghi, Claudia/0000-0002-7438-8955 FU NHLBI NIH HHS [HL71981, HL73168]; NIDDK NIH HHS [DK36836, DK60837] NR 42 TC 91 Z9 99 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2004 VL 13 IS 19 BP 2197 EP 2205 DI 10.1093/hmg/ddh233 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 854ZC UT WOS:000223941500004 PM 15282206 ER PT J AU Sugita, M Sugita, H Kaneki, M AF Sugita, M Sugita, H Kaneki, M TI Increased insulin receptor substrate 1 serine phosphorylation and stress-activated protein kinase/c-Jun N-terminal kinase activation associated with vascular insulin resistance in spontaneously hypertensive rats SO HYPERTENSION LA English DT Article DE insulin resistance; rats, spontaneously hypertensive; aorta; phosphorylation; kinase; signal transduction ID INTIMA-MEDIA THICKNESS; HOMEOSTASIS MODEL ASSESSMENT; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; WISTAR-KYOTO RATS; SKELETAL-MUSCLE; ANGIOTENSIN-II; RISK-FACTOR; IN-VIVO; CARDIOVASCULAR-DISEASE AB Insulin resistance is associated with cardiovascular disease. Impaired insulin receptor substrate (IRS)-mediated signal transduction is a major contributor to insulin resistance. Recently, IRS-1 phosphorylation at serine 307 by stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) has been highlighted as a molecular event that causes insulin resistance. We investigated IRS-1-mediated insulin signaling, IRS-1 phosphorylation at serine 307, and SAPK/JNK activation status in the aorta of spontaneously hypertensive rats (SHR) by immunoprecipitation and immunoblotting. Insulin-stimulated tyrosine phosphorylation of insulin receptor and IRS-1 in SHR was decreased to 55% (P < 0.01) and 40% (P < 0.01) of the levels in Wistar-Kyoto rats (WKY), respectively. Insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activation in SHR was reduced to 28% of the level in WKY (P < 0.0001). Immunoblot analysis revealed that phosphorylated IRS-1 at serine 307 in SHR was increased to 261% (P < 0.001) of the level in WKY. Phosphorylated ( activated) SAPK/JNK in SHR was increased to 223% of the level in WKY (P < 0.01). Serine-phosphorylated IRS-1 that was immunoprecipitated from the aorta of SHR was capable of inhibiting in vitro tyrosine phosphorylation by recombinant insulin receptor compared with WKY-derived IRS-1. These findings demonstrate that insulin resistance in the aorta of SHR was associated with elevated IRS-1 phosphorylation at serine 307 and increased SAPK/JNK activation. The present study suggests that increased SAPK/JNK activation may play an important role in the pathogenesis of vascular insulin resistance via inhibitory serine phosphorylation of IRS-1. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Room 6604, Charlestown, MA 02129 USA. EM mkaneki@partners.org FU NIDDK NIH HHS [R01DK058127] NR 51 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2004 VL 44 IS 4 BP 484 EP 489 DI 10.1161/01.HYP.0000140778.53811.20 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856PB UT WOS:000224056000023 PM 15302844 ER PT J AU Dominguez, H Storgaard, H Rask-Madsen, C Hermann, T Ihlemann, N Baunbjerg-Nielsen, D Kober, L Spohr, C Vaag, A AF Dominguez, H Storgaard, H Rask-Madsen, C Hermann, T Ihlemann, N Baunbjerg-Nielsen, D Kober, L Spohr, C Vaag, A TI Vascular and metabolic effect of neutralization of tumor necrosis factor alpha with etanercept in obese persons with type 2 diabetes SO HYPERTENSION LA English DT Meeting Abstract CT 9th Annual Meeting of the European Council for Cardiovascular Research CY OCT 01-03, 2004 CL Nice, FRANCE C1 Bispebjerg Univ Hosp, Cardiol Dept Y, Res Unit, Copenhagen, Denmark. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Rigshosp Univ Hosp, Dept Cardiol, Copenhagen, Denmark. OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2004 VL 44 IS 4 BP 571 EP 571 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856PB UT WOS:000224056000392 ER PT J AU Mora, JR von Andrian, UH AF Mora, JR von Andrian, UH TI Retinoic acid: An educational "vitamin elixir" for gut-seeking T cells SO IMMUNITY LA English DT Editorial Material ID DENDRITIC CELLS; TISSUE; EXPRESSION; MIGRATION AB T cell priming by dendritic cells (DC) from gut-associated lymphoid tissues gives rise to effector cells with pronounced gut tropism. The mechanism for DC-dependent imprinting of gut specificity has remained unknown. New findings point to retinoic acid, which is uniquely produced by intestinal DC, but not by DC from other lymphoid organs (Iwata et al., 2004; this issue of Immunity). C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mora, JR (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 NR 10 TC 33 Z9 35 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2004 VL 21 IS 4 BP 458 EP 460 DI 10.1016/j.immuni.2004.10.002 PG 3 WC Immunology SC Immunology GA 866AD UT WOS:000224744400002 PM 15485623 ER PT J AU Kotton, CN Hohmann, EL AF Kotton, CN Hohmann, EL TI Enteric pathogens as vaccine vectors for foreign antigen delivery SO INFECTION AND IMMUNITY LA English DT Review ID ATTENUATED SALMONELLA-TYPHIMURIUM; ENTEROTOXIGENIC ESCHERICHIA-COLI; HEAT-LABILE ENTEROTOXIN; VIRUS-LIKE PARTICLES; T-CELL RESPONSES; LISTERIA-MONOCYTOGENES VACCINE; HELICOBACTER-PYLORI UREASE; SYSTEMIC IMMUNE-RESPONSES; SHIGELLA-SONNEI VACCINE; CHOLERA HYBRID VACCINE C1 Massachusetts Gen Hosp, Div Infect Dis GRJ504, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis GRJ504, 55 Fruit St, Boston, MA 02114 USA. EM ckotton@partners.org FU NIAID NIH HHS [K08 AI001701]; PHS HHS [R01 51206] NR 144 TC 75 Z9 78 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2004 VL 72 IS 10 BP 5535 EP 5547 DI 10.1128/IAI.72.10.5535-5547.2004 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 857QS UT WOS:000224134000001 PM 15385450 ER PT J AU Garshick, E Laden, F Hart, JE Moy, ML AF Garshick, E Laden, F Hart, JE Moy, ML TI Respiratory symptoms and intensity of occupational dust exposure SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE occupational dust exposure; respiratory symptoms; US veterans ID GENERAL-POPULATION; ZUTPHEN AB Objectives: Occupational exposure to dusts may result in chronic respiratory symptoms. Methods: To investigate the utility of obtaining a history of occupational exposure to dust in US veterans, a respiratory health survey was conducted between 1988 and 1992 in a community-based cohort of US veterans in southeastern Massachusetts that were eligible for Veterans' Affairs (VA) healthcare benefits but were not regular users. A mail questionnaire was used to obtain a history of cough, phlegm, and wheeze, work in a dusty job, and duration, type, and intensity of dust exposure. Information on cigarette use and other possible confounders was obtained. Results: In 2,617 white men, after the data had been adjusted for cigarette smoking, age, distance to the nearest major roadway, and chronic respiratory disease, the relative odds of chronic cough, chronic phlegm, and persistent wheeze attributable to occupational dust exposure was increased twofold. Risk also increased, based on exposure intensity. For heavy dust exposure the OR was 1.98 (95% CI 1.39-2.81) for chronic cough, 2.82 (95% Cl 2.03-3.93) for chronic phlegm, and 2.70 (95% Cl 1.95-3.75) for persistent wheeze. Conclusions: After active cigarette smoking and other possible confounders had been considered, it was found that dust exposure was related to respiratory symptoms in US veterans and that the greatest risk was attributable to heavy intensity exposure. C1 VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM eric.garshick@med.va.gov FU NCI NIH HHS [R01 CA090792, R01 CA90792] NR 21 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-0131 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD OCT PY 2004 VL 77 IS 7 BP 515 EP 520 DI 10.1007/s00420-004-0534-1 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 879BG UT WOS:000225690800008 PM 15368060 ER PT J AU Royall, DR Espino, DV Polk, MJ Palmer, RF Markides, KS AF Royall, DR Espino, DV Polk, MJ Palmer, RF Markides, KS TI Prevalence and patterns of executive impairment in community dwelling Mexican Americans: results from the Hispanic EPESE Study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE aging; assessment; cognition; disability; dementia; executive functions; Hispanics ID MINI-MENTAL-STATE; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTING ILLNESSES; FUNCTIONAL STATUS; FREEDOM HOUSE; POPULATION; FEATURES; RETIREES; RATES AB Introduction Little is known about the prevalence of impaired executive control function (ECF) in community dwelling elderly or minority populations. We have determined the prevalence of cognitive impairment and impaired ECF in a community dwelling Mexican American elderly population, and their associations with functional status. Subjects Subjects were 1165 Mexican Americans age 65 and over who were administered CLOX as part of the third wave of the Hispanic Established Population for Epidemiological Study (HEPESE) conducted from 1998 to 1999. Methods ECF was measured by an executive clock-drawing task (CDT) (i.e. CLOX1). Non-executive cognitive function was assessed by the Mini-Mental State Examination (MMSE) and a non-executive CDT (CLOX2). CLOX scores were combined to estimate the prevalence of global CLOX failure (i.e. 'Type 1' cognitive impairment) vs isolated CLOX1 failure (i.e. Type 2 cognitive impairment). Results 59.3% of subjects failed CLOX1. 31.1% failed both CLOX1 and CLOX2 (Type 1 cognitive impairment). 33.3% failed CLOX1 only (Type 2 cognitive impairment). 35.6% passed both measures [no cognitive impairment (NCI)]. Many subjects with CLOX1 impairment at Wave 3 had normal MMSE scores. This was more likely to occur in the context of Type 2 cognitive impairment. Both CLOX defined cognitive impairment groups were associated with functional impairment. Conclusions A large percentage of community dwelling Mexican American elderly suffer cognitive impairment that can be demonstrated through a CDT. Isolated executive impairments appear to be most common. The ability of a CDT to demonstrate ECF impairments potentially offers a rapid, culturally unbiased and cost-effective means of assessing this domain. In contrast, the MMSE is relatively insensitive to ECF assessed by CLOX1. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div, GRECC, DRR, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX 78284 USA. Univ Texas, Med Branch, Dept Prevent Med, Galveston, TX 77550 USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Floyd Curl Dr, San Antonio, TX 78284 USA. EM royall@uthscsa.edu FU NIA NIH HHS [AG10939] NR 47 TC 20 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2004 VL 19 IS 10 BP 926 EP 934 DI 10.1002/gps.1185 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 863EQ UT WOS:000224544100002 PM 15449370 ER PT J AU Leszcz, M Sherman, A Mosier, J Burlingame, GM Cleary, T Ulman, KH Simonton, S Latif, U Strauss, B Hazelton, L AF Leszcz, M Sherman, A Mosier, J Burlingame, GM Cleary, T Ulman, KH Simonton, S Latif, U Strauss, B Hazelton, L TI Group interventions for patients with cancer and HIV disease: Part IV. Clinical and policy recommendations SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-PSYCHOTHERAPY; BREAST-CANCER; PREVENTION INTERVENTIONS; PSYCHOLOGICAL THERAPY; SERVICE PROVIDERS; SELF-MANAGEMENT; SUPPORT GROUPS; PROGRAM; OUTPATIENTS; ADJUSTMENT AB Group interventions have assumed a growing role in primary prevention and supportive care for cancer and HIV disease. Earlier sections of this Special Report examined empirical findings for these interventions and provided recommendations for future research. The current section offers brief recommendations for service providers, policy makers, and stakeholders. C1 Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada. Univ Toronto, Grp Psychotherapy, Toronto, ON M5S 1A8, Canada. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Univ Arkansas Med Sci, Program Dev Behav Med, Little Rock, AR 72205 USA. Klinikum Friedrich Schiller Univ, Inst Med Psychol, Jena, Germany. Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 3J5, Canada. RP Leszcz, M (reprint author), Mt Sinai Hosp, Dept Psychiat, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM mleszcz@mtsinai.on.ca RI Burlingame, Gary/L-2449-2014; Leszcz, Molyn/N-9043-2016 NR 48 TC 6 Z9 6 U1 2 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2004 VL 54 IS 4 BP 539 EP 556 DI 10.1521/ijgp.54.4.539.42769 PG 18 WC Psychology, Clinical SC Psychology GA 858SW UT WOS:000224213100007 PM 15388405 ER PT J AU McCluggage, WG Oliva, E Connolly, LE McBride, HA Young, RH AF McCluggage, WG Oliva, E Connolly, LE McBride, HA Young, RH TI An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; hypercalcemic small cell carcinoma; immunohistochemistry; epithelial membrane antigen; WT1 ID CORD-STROMAL TUMORS; EPITHELIAL MEMBRANE ANTIGEN; SMOOTH-MUSCLE TUMORS; NEUROECTODERMAL TUMOR; ENDOMETRIAL STROMA; DIAGNOSTIC-VALUE; CALRETININ; INHIBIN; EXPRESSION; MARKER AB Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a rare neoplasm with an aggressive behavior, broad differential diagnosis, and unknown histogenesis. To add to knowledge concerning the possible aid of immunohistochemistry in resolving problems in differential diagnosis and to further explore whether that modality points to any specific histogenesis, we undertook an immunohistochemical study of this neoplasm. Fifteen OSCCHTs (including four of the "large cell" variant) were stained with a range of antibodies, some of which have not been investigated previously in this neoplasm. Cases were stained with AE1/3, EMA, BerEP4, CK5/6, calretinin, WT1, chromogranin, CD56, synaptophysin, CD99, NB84, desmin, S100, CD10, alpha inhibin, TTFI, and p53. Staining was classified as 0 (negative), 1+ (<5% cells positive), 2+ (5% to 25% cells positive), 3+ (26% to 50% cells positive), or 4+ (>50% cells positive). All cases were positive with p53 (two 1+, five 3+, eight 4+), 14 of 15 cases were positive with WT1 (one 1+, thirteen 4+), 14 of 15 with CD10 (three 1+, four 2+, two 3+, five 4+), 13 of 15 with EMA (three 1+, three 2+, two 3+, five 4+), 11 of 15 with calretinin (nine 1+, one 3+, one 4+), 9 of 15 with AE1/3 (eight 1+, one 2+), 4 of 15 with CD56 (one 1+, two 2+, one 4+), 3 of 15 with BerEP4 (two 2+, one 4+), 2 of 15 with synaptophysin (two 1+), and 1 of 15 with S100 (4+). All cases were negative with CK5/6, chromogranin, CD99, NB84, desmin, alpha inhibin, and TTFI. The only noticeable difference in the immunophenotype between typical OSCCHT and the large cell variant was that there was 4 +EMA positivity in three of four cases of large cell variant compared with two of 11 cases of typical OSCCHT. OSCCHT is characteristically positive with AE1/3, EMA, CD10, calretinin, WT1, and p53. Combined EMA and WT1 positivity, the latter usually intense and diffuse, may be of diagnostic value, inasmuch as only a few of the neoplasms in the differential diagnosis are positive with both antibodies. Negative staining with CD99, desmin, NB84, alpha-inhibin, and TTFI may aid in the cases in which primitive neuroectodermal tumor, rhabdomyosarcoma, intraabdominal desmoplastic small round cell tumor, neuroblastoma, a sex cord-stromal tumor, and metastatic pulmonary small cell carcinoma are in the differential. Calretinin positivity precludes its use in the differential with granulosa cell tumors. The results of this investigation do not settle the issue of histogenesis, which remains enigmatic. The typical age distribution, follicle formation, and calretinin positivity are consistent with a sex cord origin. On the other hand, WT1 and EMA positivity and negative staining with alpha-inhibin would be unusual in a sex cord-stromal neoplasm and can be used as an argument for a surface epithelial origin. Germ cell and neuroendocrine origins seem highly unlikely. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@bll.n-i.nhs.uk NR 43 TC 73 Z9 80 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2004 VL 23 IS 4 BP 330 EP 336 DI 10.1097/01.pgp.0000139644.38835.9.d PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 857GF UT WOS:000224103700004 PM 15381902 ER PT J AU Carter, EA Burks, D Fischman, AJ White, M Tompkins, RG AF Carter, EA Burks, D Fischman, AJ White, M Tompkins, RG TI Insulin resistance in thermally-injured rats is associated with post-receptor alterations in skeletal muscle, liver and adipose tissue SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE insulin resistance; skeletal muscle; liver; adipose tissue ID PLECKSTRIN HOMOLOGY DOMAINS; TUMOR-NECROSIS-FACTOR; BURN INJURY; GLUCOSE-METABOLISM; CARBOHYDRATE-METABOLISM; PROTEIN CATABOLISM; GUINEA-PIGS; RECEPTOR; INFUSION; KINETICS AB Several of the possible molecular mechanisms that contribute to the insulin resistance associated with burn injury were examined in a rat model of thermal injury. Rats were subjected to full thickness scald injury (25% total body surface area, 10 sec burn) and resuscitated with saline. After 1, 2 and 3 weeks, urinary C-peptide excretion was measured in burned and sham-treated control animals. At 3 weeks after injury, glucose production by the liver and utilization by skeletal muscle was measured under insulin clamp conditions, insulin receptor binding was measured in skeletal muscle, liver and adipose tissue membranes and IRS-1 expression was measured by Western blot methods. Urinary C-peptide excretion was significantly elevated at 1, 2 and 3 weeks after injury. At 3 weeks after injury, several key metabolic processes were blunted, including the ability of insulin infusion to stimulate glucose uptake by skeletal muscle, the potency of insulin infusion for inhibiting hepatic glucose production, and the ability of a bolus injection of insulin to simulate phosphorylation of IRS-1 in liver, skeletal muscle or adipose tissue. In contrast, there were no apparent alterations in the binding of insulin to membranes from liver, skeletal muscle or adipose tissue. These findings support the concept that the burn injury stimulates insulin production 3 weeks after burn injury, and produces insulin resistance in skeletal muscle, adipose tissue and liver by processes that are associated with post-receptor alterations in the absence of changes in insulin receptor binding. C1 Shriners Hosp Children, Burns Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiobiochem, Boston, MA 02114 USA. Harvard Univ, Sch Med, Joslin Diabet Fdn, Boston, MA USA. RP Carter, EA (reprint author), Shriners Hosp Children, Burns Unit, 16 Blossom St, Boston, MA 02114 USA. EM carter.edward@mgh.harvard.edu FU NIGMS NIH HHS [2P50 GM 21700-27A1] NR 57 TC 23 Z9 26 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD OCT PY 2004 VL 14 IS 4 BP 653 EP 658 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 857GI UT WOS:000224104000025 PM 15375597 ER PT J AU Weisbart, RH Wakelin, R Chan, G Miller, CW Koeffler, PH AF Weisbart, RH Wakelin, R Chan, G Miller, CW Koeffler, PH TI Construction and expression of a bispecific single-chain antibody that penetrates mutant p53 colon cancer cells and binds p53 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE antibodies; cell trafficking; cytotoxicity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MONOCLONAL-ANTIBODY; DNA ANTIBODIES; LIVING CELLS; RESTORATION; PROTEIN; TRANSFECTION; FRAGMENTS; PEPTIDES; DELIVERY AB A bispecific, single-chain antibody Fv fragment (BsscFv) was constructed from a single-chain Fv fragment of mAb 3E10 that penetrates living cells and localizes in the nucleus, and a single-chain Fv fragment of a non-penetrating antibody, mAb PAb421 that binds the C-terminal of p53. PAb421 binding restores wild-type functions of some p53 mutants, including those of SW480 human colon cancer cells. The BsscFv penetrated SW480 cells and was cytotoxic, suggesting an ability to restore activity to mutant p53. COS-7 cells (monkey kidney cells with wild-type p53) served as a control since they are unresponsive to PAb421 due to the presence of SV40 large T antigen that inhibits binding of PAb421 to p53. Bs-scFv penetrated COS-7 cells but was not cytotoxic, thereby eliminating non-specific toxicity of Bs-scFv unrelated to binding p53. A single mutation in CDR1 of PAb421 VH eliminated binding of the Bs-scFv to p53 and abrogated cytotoxicity for SW480 cells without altering cellular penetration, further supporting the requirement of PAb421 binding to p53 for cytotoxicity. Our study demonstrates the use of an antibody that penetrates living cells in the design of a bispecific single chain antibody to target and restore the function of an intracellular protein. C1 Vet Affairs Greater Los Angeles Hlth Care Syst 11, Dept Med, Div Rheumatol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Cedars Sinai Res Inst Ctr, Los Angeles, CA 90048 USA. RP Weisbart, RH (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst 11, Dept Med, Div Rheumatol, 1611 Plummer St, Sepulveda, CA 91343 USA. EM rweisbar@ucla.edu NR 22 TC 15 Z9 15 U1 1 U2 4 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2004 VL 25 IS 4 BP 1113 EP 1118 PG 6 WC Oncology SC Oncology GA 856VP UT WOS:000224073700037 PM 15375563 ER PT J AU Backman, L Sandblom, J Gavazzeni, J Nyberg, L Fransson, P Wright, CI Ingvar, M Fischer, H AF Backman, L Sandblom, J Gavazzeni, J Nyberg, L Fransson, P Wright, CI Ingvar, M Fischer, H TI Age differences in brain activation during emotional processing: Converging evidence from perception and memory SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 Karolinska Inst, S-10401 Stockholm, Sweden. Karolinska Hosp, S-10401 Stockholm, Sweden. Umea Univ, S-90187 Umea, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD OCT-DEC PY 2004 VL 39 IS 5-6 SU S BP 229 EP 229 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 884WS UT WOS:000226118002085 ER PT J AU Shih, HA Jiang, SB Aljarrah, KM Doppke, KP Choi, NC AF Shih, HA Jiang, SB Aljarrah, KM Doppke, KP Choi, NC TI Internal target volume determined with expansion margins beyond composite gross tumor volume in three-dimensional conformal radiotherapy for lung cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE lung cancer; tumor movement associated with respiration; internal target volume; gross tumor volume; composite tumor volume; 3D-CRT; CT scan; geographic miss ID INSPIRATION BREATH-HOLD; THERAPY ONCOLOGY GROUP; PHASE-I/II TRIAL; RADIATION-THERAPY; DOSE-ESCALATION; CARCINOMA; MOVEMENT; MOTION; PROBABILITY; SURVIVAL AB Purpose: Gross tumor volume (GTV) of lung cancer defined by fast helical CT scan represents an image of moving tumor captured at a point in active respiratory movement. However, the method for defining internal margins beyond GTV to account for its expected physiologic movement and all variations in size and shape during the administration of radiation has not been established. The goal of this study was to determine the internal margins with expansion margins beyond individual GTVs defined with (1) fast scan at shallow free breathing, (2) breath-hold scans at the end of tidal volume inspiration and expiration, and (3) 4-s slow scan to approximate the composite GTV of all scans. Methods and Materials: A series of sequential CT scans were acquired with (1) a fast helical scan at shallow free breathing and (2) breath-hold scans at the end of tidal volume expiration and inspiration for the first 6 patients, and (3) a 4-s slow scan at quiet free breathing, which was added for the latter 7 patients. We fused breath-hold scans and the 4-s slow scan to the fast scan at shallow free breathing to generate the composite GTV. Margins necessary to encompass the composite GTV beyond individual GTVs defined by either fast scan at quiet free breathing, breath-hold scans, or the 4-s slow scan at quiet free breathing were defined as expansion or internal margins and termed the internal target volumes. The centroid of the tumor volume was also used as another reference for tumor movement. Results: Thirteen patients with 14 tumors were enrolled into the study. Substantial tumor movement was noted by either the extent of internal margins beyond each GTV or the movement of the centroid. Internal margins varied significantly according to the method of CT scanning for determination of GTV. Even for tumors in the same lobe of the lung, a wide range of internal margins and significant variation in the centroid movement in all directions (x, y, and z) were observed. The GTV of a single fast helical scan at free breathing (n = 14) required the largest internal margin (mean, 3.5 mm; maximum, 18 mm; standard deviation [SD], 4.2 mm) to match the composite GTV, compared with those of the 4-s slow scan (mean 2.7 mm, maximum 14 mm, SD 3.5 mm) or combined breath-hold scans (mean 1.1 mm, maximum 9 mm, SD 1.9 mm). Internal margins (expansion margins) required to approximate the composite GTV in 95% of cases were 13 mm, 10 mm, and 5 mm for the GTVs of a single fast scan, 4-s slow scan, and breath-hold scans at the end of tidal volume inspiration and expiration, respectively. Conclusions: The internal margins required to account for the internal tumor motion in three-dimensional conformal radiotherapy are substantial. For the use of symmetric and population-based margins to account for internal tumor motion, GTV defined with breath-bold scans at the end of tidal volume inspiration and expiration has a narrower range of internal margins in all directions than that of either a single fast scan or 4-s slow scan. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Choi, NC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM nchoi@partners.org FU NIBIB NIH HHS [EB00290] NR 32 TC 44 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2004 VL 60 IS 2 BP 613 EP 622 DI 10.1016/j.ijrobp.2004.05.031 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 855IJ UT WOS:000223966500035 PM 15380599 ER PT J AU Cubilla, AL Velazquez, EF Young, RH AF Cubilla, AL Velazquez, EF Young, RH TI Epithelial lesions associated with invasive penile squamous cell carcinoma: A pathologic study of 288 cases SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE penis; squamous hyperplasia; precancerous lesions; squamous intraepithelial lesion; penile intraepithelial neoplasia ID VULVAR INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS DNA; CLINICAL PRESENTATION; PREMALIGNANT LESIONS; BOWENS DISEASE; NECK-CANCER; INSITU; ERYTHROPLASIA; HYPERPLASIAS; PREVALENCE AB A heterogeneous spectrum of epithelial alterations and atypical lesions affect the squamous epithelium of penile mucosal anatomical compartments. Analogous to other genital sites, the terminology utilized to define the lesions is variable. The few pathologic studies of penile precancerous lesions are mostly related to carcinoma in situ and human papilloma Virus (HPV), and the information on low-grade atypical lesions is limited. The objective of this study was to comprehensively describe the morphologic features of all epithelial alterations, benign and atypical, low grade and high grade, associated with invasive squamous cell carcinoma of the penis and to investigate their relation with each other and with subtypes of invasive carcinoma. We also propose herein a simple and reproducible nomenclature for penile precancerous abnormalities until more biological, molecular, or epidemiologic information on the lesions is available. Two hundred and eighty-eight penectomy and circumcision specimens with invasive squamous cell carcinoma were pathologically evaluated. Carcinomas were classified as usual, verrucous, papillary not otherwise specified, warty (condylomatous), basaloid, and mixed. Associated lesions were classified as squamous hyperplasia and squamous intraepithelial lesions of low and high grade (LGSIL and HGSIL). In LGSIL, atypia was confined to the lower third, and in HGSIL, atypical cells affected at least two thirds of the squamous epithelium. Subtypes of SIL were squamous, warty, basaloid, warty-basaloid, and papillary. Squamous hyperplasia, the most common lesion, was found in 83% of the cases, followed by LGSIL (59%) and HGSIL (44%). In 62% of the cases more than 1 associated lesion was present per specimen. A sequence from squamous hyperplasia to low-grade to high-grade SIL was seen frequently. Squamous hyperplasia was more commonly associated with usual squamous, papillary, and verrucous than with warty and basaloid invasive carcinomas. LGSIL was associated with all types of squamous cell carcinoma but was rarely present adjacent to basaloid or verrucous tumors. HGSIL was present in two thirds of invasive warty, basaloid, and mixed warty-basaloid tumors, in about half of usual squamous cell carcinomas, and was absent in papillary and verrucous carcinomas. Correlation of special types of invasive carcinomas with subtypes of SIL revealed morphologic correspondence of invasive tumor and the associated intraepithelial lesion. Squamous LGSIL was preferentially associated with verrucons, papillary, an usual squamous cell carcinomas; warty LGSIL, with invasive warty and mixed warty-basaloid carcinomas. High-grade SIL of the squamous type was frequently found in squamous cell carcinoma of usual type but was rarely present with warty or basaloid carcinomas. Basaloid HGSIL was associated with basaloid carcinoma, and HGSIL of warty type, with either warty or mixed warty-basaloid carcinomas. The high frequency of squamous hyperplasia and LGSIL and preferential association with usual, verrucous, and papillary carcinomas plus the subtle morphologic differences of the 2 lesions suggest that, despite its benign appearance, squamous hyperplasia is a precursor of the aforementioned carcinomas. The association and histologic similarities between high-grade SIL of the basaloid, warty, or mixed forms with their invasive counterparts indicate these lesions are their likely precursors. C1 NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. Univ Nacl Asuncion, Fac Ciencias Med, Inst Patol & Invest, Asuncion, Paraguay. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Velazquez, EF (reprint author), NYU, Med Ctr, Dept Pathol, 560 1st Ave,TISCH 461, New York, NY 10016 USA. NR 42 TC 38 Z9 40 U1 2 U2 3 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2004 VL 12 IS 4 BP 351 EP 364 DI 10.1177/106689690401200408 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA 869QI UT WOS:000224998700008 PM 15494861 ER PT J AU Clark, RA Epperson, TK Valente, AJ AF Clark, RA Epperson, TK Valente, AJ TI Mechanisms of activation of NADPH oxidases SO JAPANESE JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th International Peroxidase Meeting CY OCT 27-30, 2004 CL Kyoto, JAPAN AB The members of the NOX family of enzymes are expressed in a variety of tissues and serve a number of functions. There is a high level of conservation of primary protein sequence, as well as functional features, although specialized responses are beginning to emerge. In this context, our data demonstrate that the NOX1 cytoplasmic domains interact efficiently with the cytoplasmic subunits of the phagocyte NADPH oxidase and identify the second cytoplasmic loop of NOX electron transporters as a crucial domain for enzyme function. Studies of cytosolic co-factors showed that the C-terminal cytoplasmic domain of NOX1 was absolutely required for activation with NOXO1 and NOXA1 and that this activity required interaction of the putative NADPH-binding region of this domain with NOXA1. Finally, we have provided the first example of how alternative splicing of a NOX co-factor may be involved in the regulation of NADPH oxidase function. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78284 USA. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78284 USA. EM clarkra@uthscsa.edu NR 4 TC 11 Z9 11 U1 0 U2 0 PU NATL INST INFECTIOUS DISEASES PI TOKYO PA JPN J INFECT DIS ED OFF NATL INST INFECTIOUS DISEASES TOYAMA 1-23-1, SHINJUKU-KU, TOKYO, 162-8640, JAPAN SN 1344-6304 EI 1884-2836 J9 JPN J INFECT DIS JI Jpn. J. Infect. Dis. PD OCT PY 2004 VL 57 IS 5 BP S22 EP S23 PG 2 WC Infectious Diseases SC Infectious Diseases GA 867WE UT WOS:000224872600027 PM 15507761 ER PT J AU Parameswaran, V Schumacher, HR AF Parameswaran, V Schumacher, HR TI An Ayurvedic-Derived Osteoarthritis treatment - What can this teach us? SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Editorial Material ID ANTIINFLAMMATORY AGENT; RHEUMATOID-ARTHRITIS; DIFERULOYL METHANE; BOSWELLIA SERRATA; CURCUMIN; ACIDS; MEDICINE; EXTRACT; SYSTEM C1 Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Parameswaran, V (reprint author), Univ Penn, Sch Med, Div Rheumatol, 533 Maloney Bldg, Philadelphia, PA 19104 USA. EM pvid@yahoo.com NR 25 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2004 VL 10 IS 5 BP 231 EP 233 DI 10.1097/01.rhu.0000136090.53441.0b PG 3 WC Rheumatology SC Rheumatology GA 860TY UT WOS:000224367400001 PM 17043518 ER PT J AU Cohen, AN Hammen, C Henry, RM Daley, SE AF Cohen, AN Hammen, C Henry, RM Daley, SE TI Effects of stress and social support on recurrence in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; social support; life events; recurrence ID LIFE EVENTS AB Background: Limited research has examined the impact of social support on the course of bipolar disorder, although results suggest a probable link. This study examines prospectively the effects of stressful events and social support on episode recurrence in bipolar I disorder. Methods: Fifty-two outpatients with bipolar I disorder recruited from an urban community were followed every 3 months for up to 1 year. At the initial interview, individuals reported separately on perceived social support from a best friend, parent, and romantic partner, combined to form a total network support score. Ongoing prospective assessments of stressful life events, symptomatology, and medication compliance were completed over I year. Logistic regressions were utilized to predict episode recurrence. Results: As predicted, both higher levels of stress and lower levels of social support from the total network independently predicted depressive recurrence over a 1-year follow-up, after controlling for clinical history and compliance. Social support did not moderate the impact of stress. Limitations: Only a 1-year follow-up was obtained, and sample sizes may have been insufficient to detect prediction of manic episodes. Direction of causality between support and recurrence is hypothesized but cannot be definitively determined. Conclusions: Higher levels of stress and perceptions of less available and poorer quality close relationships are associated with recurrence. Interventions that target these psychosocial vulnerabilities may help alter the course of bipolar 1 disorder. Research with larger samples should further examine the possible polarity-specific effects of social risk factors. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. W Los Angeles Va Healthcare Ctr, Los Angeles, CA USA. Mental Illness Educ & Clin Ctr, Los Angeles, CA USA. RP Hammen, C (reprint author), Univ Calif Los Angeles, Dept Psychol, 405 Hilgard Ave, Los Angeles, CA 90095 USA. EM hammen@psych.ucla.edu FU NIMH NIH HHS [MH-14584] NR 12 TC 63 Z9 64 U1 3 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT 1 PY 2004 VL 82 IS 1 BP 143 EP 147 DI 10.1016/j.jad.2003.10.008 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 864YY UT WOS:000224670500019 PM 15465589 ER PT J AU Biederman, J Faraone, SV Wozniak, J Mick, E Kwon, A Aleardi, M AF Biederman, J Faraone, SV Wozniak, J Mick, E Kwon, A Aleardi, M TI Further evidence of unique developmental phenotypic correlates of pediatric bipolar disorder: findings from a large sample of clinically referred preadolescent children assessed over the last 7 years SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Bipolar Disorder CY MAR 21, 2003 CL Washington, DC SP NIMH DE bipolar disorder; mania; ADHD; comorbidity; children ID MANIC-DEPRESSIVE ILLNESS; DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE FOLLOW-UP; PREPUBERTAL CHILDREN; JUVENILE MANIA; THERAPEUTIC CONSIDERATIONS; ANXIETY DISORDERS; MAJOR DEPRESSION; CONDUCT DISORDER; COMMUNITY SAMPLE AB Background: A comparison of the prevalence, clinical correlates, and patterns of comorbidity among children with bipolar disorder (BPD) assessed in the early 1990s (1st cohort) with those evaluated over the last 7 years (2nd cohort). Method: Subjects in both cohorts were children aged : 12 years referred to a child psychiatry service and evaluated with identical assessment methods. Children with a DSM-III-R BPD diagnosis (1st cohort, n=43; 2nd cohort, n=129) were identified. For comparison purposes, we used aftention-deficit/hyperactivity disorder (ADHD) children without BPD referred to the same clinic during the same time period (1st cohort, n=164; 2nd cohort, n=450). Results: Analogous to 1st cohort findings, 2nd cohort results showed that (1) mania was identified in 17% of subjects; (2) the clinical picture was predominantly irritable and mixed, and the course was chronic; (3) BPD children frequently met criteria for major depression, ADHD, psychosis, and anxiety disorders; and (4) BPD children had high rates of psychiatric hospitalization and had evidence of severely impaired psychosocial functioning. Conclusion: These findings confirm that pediatric BPD is a severe clinical disorder afflicting a sizable number of referred preadolescent children. Its unique phenotypic features and patterns of comorbidity support the hypothesis that clinically referred pediatric bipolar disorder represents a very severe developmental subtype of bipolar disorder. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Study Pediat Psychopathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stanley Ctr Treatment Pediat Bipolar Disorder, Boston, MA 02114 USA. Massachusetts Gen Hosp, Prechter Ctr Genet Pediat Bipolar Disorder, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02114 USA. RP Biederman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Dept Psychiat, WACC 725,Warren 705,15 Parkman St, Boston, MA 02114 USA. EM biederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 65 TC 61 Z9 64 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2004 VL 82 SU 1 BP S45 EP S58 DI 10.1016/j.jad.2004.05.021 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 884WO UT WOS:000226117600006 PM 15571789 ER PT J AU Biederman, J Mick, E Faraone, SV Van Patten, S Burback, M Wozniak, J AF Biederman, J Mick, E Faraone, SV Van Patten, S Burback, M Wozniak, J TI A prospective follow-up study of pediatric bipolar disorder in boys with attention-deficit/hyperactivity disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Bipolar Disorder CY MAR 21, 2003 CL Washington, DC SP NIMH DE boys; bipolar disorder; pediatric; attention-deficit hyperactivity disorder ID DEFICIT HYPERACTIVITY DISORDER; PREPUBERTAL CHILDREN; ONSET; CHILDHOOD; SYMPTOMS; MANIA; ADHD; ADOLESCENTS; MISTAKEN; PROBANDS AB Objective: To examine patterns of persistence and remission in pediatric bipolar disorder attending to syndromatic, symptomatic, functional and affective definitions of remission of bipolar symptomatology in a longitudinal sample of ADHD children with comorbid bipolar disorder. Methods: ADHD boys (128) were followed over 1- and 4-year follow-up assessments with structured diagnostic interviews to assess the persistence of psychiatric comorbidity. The course and duration of bipolar disorder was estimated by calculating the time from age at onset and the age at remission reported at either the 1- or 4-year follow-up assessments. Results: Twenty-two (17%, Prevalent Cases) subjects met criteria for bipolar disorder at the baseline assessment. The average age of these subjects was 10.5+/-3.0 (range: 6 to 17 years) at baseline and 14.4+/-3.1 years of age at follow-up. The rate of remission was heavily dependent on the definition used. The rate of functional remission was the lowest and the rate of syndromatic remission was the highest. Regardless of the definition used, however, the disorder was chronic and lasted many years. Limitations: These data should be considered preliminary due to the sample size and the absence of mood symptom rating scales. Conclusions: That less than 20% of subjects attained functional remission or euthymia over the entire time period evaluated provides further evidence that pediatric bipolar disorder is a chronic mood disorder with a poor prognosis. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Study Pediat Psychopathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stanley Med Res Inst, Ctr Pediat Bipolar Disorder Res, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725,15 Parkman St,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD036317]; NIMH NIH HHS [K08MH001503, K01MH065523] NR 33 TC 40 Z9 40 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2004 VL 82 SU 1 BP S17 EP S23 DI 10.1016/j.jad.2004.05.012 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 884WO UT WOS:000226117600003 PM 15571786 ER PT J AU Biederman, J James, R AF Biederman, J James, R TI Furthering the scientific foundation of pediatric bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Warren 705,15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2004 VL 82 SU 1 BP S1 EP S3 DI 10.1016/j.jad.2004.05.011 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 884WO UT WOS:000226117600001 PM 15571783 ER PT J AU Faraone, SV Su, J Tsuang, MT AF Faraone, SV Su, J Tsuang, MT TI A genome-wide scan of symptom dimensions in bipolar disorder pedigrees of adult probands SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Bipolar Disorder CY MAR 21, 2003 CL Washington, DC SP NIMH DE symptom dimensions; bipolar disorder; linkage analysis ID LINKAGE ANALYSIS; MANIA; GENETICS; ILLNESS; SCHIZOPHRENIA; PHENOMENOLOGY; SIGNS; TWIN AB Although twin and adoption show bipolar disorder (BP) has a strong genetic component, few chromosomal regions have been consistently implicated by molecular genetic studies. To address this issue, we sought to determine if quantitative dimensions of bipolar disorder symptoms would be useful for detecting genes that underlie the susceptibility to bipolar disorder. Subjects were 520 individuals diagnosed with bipolar I, bipolar II or schizoaffective disorder, bipolar type who had participated in the NIMH genetics initiative for bipolar disorder. We constructed symptom scores from 29 psychiatric symptoms recorded in the Diagnostic Interview for Genetic Studies (DIGS). Principal components factor analysis followed by a varimax rotation was used to extract symptom dimensions. Factor scores were calculated for all genotyped individuals in the sample, regardless of affection status. Heritable factors were used in a variance-components linkage analysis, which utilized the exact likelihoods of allele-sharing identical-by-descent for each pair of relatives within each pedigree. The principal components factor analysis resulted in five independent dimensions: depressed state, psychosis, sleep disturbances, psychomotor acceleration, and irritability. Two factors were significantly heritable: depression (h(2)=0.53, p<0.001) and irritable vs. euphoric mania (h(2)=0.35, p=0.03). These were subsequently used in a linkage analysis that resulted in LOD scores of <2.0, which are not statistically significant. The five constructs developed through factor analysis appear to be consistent with previous factor analyses. Notably, only the dimensions associated with the type of mood disturbance showed high heritability, which suggests that careful measurements of depression, euphoria and irritability may be particularly useful in clarifying the genetic etiology of bipolar disorder in future studies. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Pediat Psychopathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Faraone, SV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, WRN 705,55 Fruit St, Boston, MA 02114 USA. EM sfaraone@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R01MH43518, R01MH57934, R01MH59624, R01MH60485, R13MH59126] NR 37 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2004 VL 82 SU 1 BP S71 EP S78 DI 10.1016/j.jad.2004.05.015 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 884WO UT WOS:000226117600008 PM 15571792 ER PT J AU Wozniak, J Spencer, T Biederman, J Kwon, A Monuteaux, M Rettew, J Lail, K AF Wozniak, J Spencer, T Biederman, J Kwon, A Monuteaux, M Rettew, J Lail, K TI The clinical characteristics of unipolar vs. bipolar major depression in ADHD youth SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Bipolar Disorder CY MAR 21, 2003 CL Washington, DC SP NIMH ID DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE FOLLOW-UP; RISK-FACTORS; EARLY-ONSET; FAMILY; ADOLESCENTS; PREDICTORS; CHILDREN; ANTIDEPRESSANTS; AUGMENTATION AB Objective: To investigate the characteristics of unipolar vs. bipolar depression in youth using a sample of children referred for a study on attention deficit hyperactivity disorder (ADHD). Methods: We compared children with unipolar depression (N=109) to those with bipolar depression (N=43) using boys and girls (N=280) referred for a study on ADHD. Comparisons were made in characteristics of depression, comorbidity and family history. All diagnoses were made using the KSADS-E. Results: In comparison to children with unipolar depression, children with bipolar depression were more likely to have met criteria for depression due to both "sad" and "mad" mood states as stated in the KSADS-E, have severe depression with suicidality, anhedonia and hopelessness. Children with bipolar depression were more likely to have comorbid conduct disorder, severe oppositional defiant disorder, agoraphobia, obsessive compulsive disorder and alcohol abuse, compared to children with unipolar depression. Bipolar depressed children had lower GAF scores and higher rates of hospitalization. Bipolar depression is associated with higher levels of psychiatric disorders in first-degree relatives. Conclusions: In youth, bipolar depression is distinct from unipolar depression in quality and severity of symptoms, comorbidity and family history. This presentation can aid clinicians in identifying children and adolescents with bipolar disorder. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, ACC 725, Boston, MA 02114 USA. EM jwozniak@partners.org NR 36 TC 35 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2004 VL 82 SU 1 BP S59 EP S69 DI 10.1016/j.jad.2004.05.013 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 884WO UT WOS:000226117600007 PM 15571791 ER PT J AU Muratoglu, OK Bragdon, CR Jasty, M O'Connor, DO Von Knoch, RS Harris, WH AF Muratoglu, OK Bragdon, CR Jasty, M O'Connor, DO Von Knoch, RS Harris, WH TI Knee-simulator testing of conventional and cross-linked polyethylene tibial inserts SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; highly cross-linked polyethylene; wear; oxidation; knee simulator ID MOLECULAR-WEIGHT POLYETHYLENE; MECHANICAL-PROPERTIES; CLINICAL-PERFORMANCE; GAMMA-STERILIZATION; WEAR; REPLACEMENTS; HIP; OXIDATION; IMPACT AB We compared the resistance to delamination and to adhesive/abrasive wear of conventional and highly cross-linked polyethylene tibial inserts of a cruciate-retaining total knee design using a knee simulator. Both groups were tested after aggressive, accelerated aging, and I set of conventional inserts was studied without aging. Aging oxidized the conventional, but riot the highly cross-linked, inserts. The simulated normal gait testing lasted for 5 and 10 million cycles for the conventional and highly cross-linked inserts, respectively. Aged conventional inserts showed delaminations, whereas none were observed in the unaged conventional and aged cross-linked inserts. Wear rates measured by the gravimetric method were 9 +/- 2 mm(3), 10 +/- 4 mm(3), and 1 +/- 0 mm(3) per million cycles; by the metrologic method, they were 8 +/- 1 mm(3), 9 +/- 2 mm(3), and 3 +/- 0 mm(3) for the unaged conventional, aged conventional, and aged highly crosslinked inserts, respectively. in the test model used, oxidation led to delamination, whereas increased cross-link density resulted in reduced adhesive/abrasive wear of tibial inserts. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1206,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 85 Z9 88 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2004 VL 19 IS 7 BP 887 EP 897 DI 10.1016/j.arth.2004.03.019 PG 11 WC Orthopedics SC Orthopedics GA 865XG UT WOS:000224736900013 PM 15483806 ER PT J AU Wetzel, RK Pascoa, JL Arystarkhova, E AF Wetzel, RK Pascoa, JL Arystarkhova, E TI Stress-induced expression of the gamma subunit (FXYD2) modulates Na, K-ATPase activity and cell growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MURINE KIDNEY-CELLS; SMOOTH-MUSCLE-CELLS; IMMUNOCYTOCHEMICAL LOCALIZATION; RENAL NA,K-ATPASE; GENE-EXPRESSION; HYPERTONIC STRESS; FUNCTIONAL-ROLE; OSMOTIC-STRESS; MESSENGER-RNAS AB In kidney, the Na,K-ATPase is associated with a single span protein, the gamma subunit (FXYD2). Two splice variants are differentially expressed along the nephron and have a differential influence on Na,K-ATPase when stably expressed in mammalian cells in culture. Here we used a combination of gene induction and gene silencing techniques to test the functional impact of gamma by means other than transfection. NRK-52E cells (of proximal tubule origin) do not express gamma as a protein under regular tissue culture conditions. However, when they were exposed to hyperosmotic medium, induction of only the gammaa splice variant was observed, which was accompanied by a reduction in the rate of cell division. Kinetic analysis of stable enzyme properties from control (alpha1beta1) and hypertonicity-treated cultures (alpha1beta1gammaa) revealed a significant reduction (up to 60%) of Na,K-ATPase activity measured under V-max conditions with little or no change in the amounts of alpha1beta1. This effect as well as the reduction in cell growth rate was practically abolished when gamma expression was knocked down using specific small interfering RNA duplexes. Surprisingly, a similar induction of endogenous gammaa because of hypertonicity was seen in rat cell lines of other than renal origin: C6 (glioma), PC12 (pheochromocytoma), and L6 (myoblasts). Furthermore, exposure of NRK-52E cells to other stress inducers such as heat shock, exogenous oxidation, and chemical stress also resulted in a selective induction of gammaa. Taken together, the data imply that induction of gammaa may have adaptive value by being a part of a general cellular response to genotoxic stress. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Wellman 415,55 Fruit St, Boston, MA 02114 USA. EM aristarkhova@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL-36271] NR 62 TC 32 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 2004 VL 279 IS 40 BP 41750 EP 41757 DI 10.1074/jbc.M405622200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 856WG UT WOS:000224075500063 PM 15280368 ER PT J AU Seo, SY Chen, YB Ivanovska, I Ranger, AM Hong, SJ Dawson, VL Korsmeyer, SJ Bellows, DS Fannjiang, Y Hardwick, JM AF Seo, SY Chen, YB Ivanovska, I Ranger, AM Hong, SJ Dawson, VL Korsmeyer, SJ Bellows, DS Fannjiang, Y Hardwick, JM TI BAD is a pro-survival factor prior to activation of its pro-apoptotic function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID SUBSTITUTION; CELL-DEATH; CYTOCHROME-C; BCL-2 FAMILY; MITOCHONDRIAL APOPTOSIS; ALPHAVIRUS INFECTION; CLEAVAGE; PROTEIN; CONVERSION; MICE AB The mammalian BAD protein belongs to the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overexpressed BAD(L) can inhibit cell death in neurons and other cell types. Several mechanisms regulate the conversion of BAD from an anti-death to a pro-death factor, including alternative splicing that produces the N-terminally truncated BAD(S). In addition, caspases convert BAD(L) into a pro-death fragment that resembles the short splice variant. The caspase site that is selectively cleaved during cell death following growth factor (interleukin-3) withdrawal is conserved between human and murine BAD. A second cleavage site that is required for murine BAD to promote death following Sindbis virus infection, gamma-irradiation, and staurosporine treatment is not conserved in human BAD, consistent with the inability of human BAD to promote death with these stimuli. However, loss of the BAD N terminus by any mechanism is not always sufficient to activate its pro-death activity, suggesting that the N terminus is a regulatory domain rather than an anti-death domain. These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death. C1 Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hardwick, JM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, E5140 BSPH,615 N Wolfe St, Baltimore, MD 21205 USA. EM hardwick@jhu.edu OI Dawson, Valina/0000-0002-2915-3970 FU NINDS NIH HHS [R01 NS034175, NS34175, NS37402, R01 NS037402] NR 48 TC 36 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 2004 VL 279 IS 40 BP 42240 EP 42249 DI 10.1074/jbc.M406775200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 856WG UT WOS:000224075500116 PM 15231831 ER PT J AU DeFrate, LE Sun, H Gill, TJ Rubash, HE Li, GA AF DeFrate, LE Sun, H Gill, TJ Rubash, HE Li, GA TI In vivo tibiofemoral contact analysis using 3D MRI-based knee models SO JOURNAL OF BIOMECHANICS LA English DT Article DE in vivo knee kinematics; cartilage contact; soft tissue biomechanics; magnetic resonance imaging; imaging ID ANTERIOR CRUCIATE LIGAMENT; MAGNETIC-RESONANCE IMAGES; PATELLOFEMORAL JOINT; CARTILAGE THICKNESS; Q-ANGLE; KINEMATICS; POSTERIOR; RECONSTRUCTION; AREAS; ROTATION AB This paper quantified the motion of the tibiofemoral contact points during in vivo weight bearing flexion using MRI-based 3D knee models and two orthogonal fluoroscopic images. The contact points on the medial and lateral tibial plateau were calculated by finding the centroid of the intersection of the tibial and femoral cartilage layers and by using the bony geometry alone. Our results indicate that the medial femoral condyle remains in the central portion of the tibial plateau and the lateral condyle translates posteriorly with increasing flexion. Using the bony contact model increased the total translation of the medial and lateral condyles by 250 and 55%, respectively, compared to the cartilage contact model. These results suggest that using the bony geometry alone may not accurately represent the articular surfaces of the knee. Articular cartilage geometry may have to be used to accurately quantify tibiofemoral contact. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM glil@partners.org NR 32 TC 105 Z9 112 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD OCT PY 2004 VL 37 IS 10 BP 1499 EP 1504 DI 10.1016/j.jbiomech.2004.01.012 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 855YJ UT WOS:000224010500005 PM 15336924 ER PT J AU Battaglino, RA Joe, M Spate, U Sharma, A Graves, D Kohler, T Muller, R Stashenko, P AF Battaglino, RA Joe, M Spate, U Sharma, A Graves, D Kohler, T Muller, R Stashenko, P TI Role of the serotonin transporter (5-HTT) in bone metabolism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. Boston Univ, Sch Dent Med, Boston, MA 02215 USA. ETH, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S64 EP S64 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800245 ER PT J AU Bischoff, DS Makhijani, N Zhu, J Tachiki, K Yamaguchi, DT AF Bischoff, DS Makhijani, N Zhu, J Tachiki, K Yamaguchi, DT TI ELR+ CXC chemokine production by and action in human mesenchymal stem cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S132 EP S132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800516 ER PT J AU Burnett, SM Gunawardene, S Bringhurst, FR Jueppner, H Finkelstein, JS AF Burnett, SM Gunawardene, S Bringhurst, FR Jueppner, H Finkelstein, JS TI The effects of dietary phosphate on the regulation of FGF-23 in humans. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S252 EP S252 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801362 ER PT J AU Chen, T Rodriguez, L Chang, W Shoback, D AF Chen, T Rodriguez, L Chang, W Shoback, D TI Ca2+-sensing by cell populations in murine bone marrow: Effects on osteoclast formation and gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S155 EP S155 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800611 ER PT J AU Christian, RC Elliott, ME Vallarta-Ast, N Hansen, K AF Christian, RC Elliott, ME Vallarta-Ast, N Hansen, K TI Efficacy and safety of long-term alendronate in male solid organ transplant recipients. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Wisconsin, Madison, WI 53706 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 SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S172 EP S172 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801037 ER PT J AU Dean, T Linglart, A Bastepe, M Mahon, M Potts, JT Jueppner, H Gardella, TJ AF Dean, T Linglart, A Bastepe, M Mahon, M Potts, JT Jueppner, H Gardella, TJ TI G protein dependent binding of a PTH(1-15) analog radioligand to the juxtamembrane portion of the PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S339 EP S339 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802053 ER PT J AU Franco, GEL Stone, DS Blank, RD AF Franco, GEL Stone, DS Blank, RD TI Young's modulus of C57BL/6J cortical bone is less than that of Outbred Col1aI(oim) heterozygotes or their wild-type littermates. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Wisconsin, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RI Stone, Donald/A-7496-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S223 EP S223 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801243 ER PT J AU Frohlich, LF Chung, UI Guo, J Juppner, H AF Frohlich, LF Chung, UI Guo, J Juppner, H TI A mouse model of Jansen metaphyseal chondrodysplasia (JMC): Introduction of the H223R mutation into the murine PTH/PTHrP receptor gene results in delayed endochondral bone formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, Endocrine Unit, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S61 EP S61 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800234 ER PT J AU Gensure, RC Makitie, O Barclay, C Chan, C DePalmer, S Bastepe, M Abuzahra, H Couper, R Seidman, J Cole, WG Juppner, H AF Gensure, RC Makitie, O Barclay, C Chan, C DePalmer, S Bastepe, M Abuzahra, H Couper, R Seidman, J Cole, WG Juppner, H TI A novel COL1A1 mutation causes autosomal dominant infantile cortical hyperostosis (Caffey disease). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Tulane Univ, Dept Pediat, New Orleans, LA 70118 USA. Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. Harvard Univ, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Adelaide, Womens & Childrens Hosp, Dept Paediat, Adelaide, SA, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S27 EP S27 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800103 ER PT J AU Ghosh-Choudhury, N AF Ghosh-Choudhury, N TI Statins stimulate phosphatidylinositol 3 kinase (PI 3 K) signaling during osteoblast differentiation: A mechanism of new bone formation in osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S274 EP S274 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801456 ER PT J AU Goel, N Orces, CH Lee, S AF Goel, N Orces, CH Lee, S TI Hip fracture trends from 1990-2001: Indirect evidence of improved diagnosis and treatment SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. S Texas Vet Hlth Syst, Laredo, TX USA. S Texas Vet Hlth Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 MA M353 BP S428 EP S428 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802425 ER PT J AU Guo, J Bringhurst, FR Kronenberg, HM AF Guo, J Bringhurst, FR Kronenberg, HM TI PTH receptor activates Wnt/beta-catenin signaling pathway in growth plate chondrocytes ex vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S338 EP S338 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802050 ER PT J AU Guo, J Bringhurst, FR Kronenberg, HM AF Guo, J Bringhurst, FR Kronenberg, HM TI alpha 1 collagen promoter-directed overexpression of Dkk1 in mice causes dwarfism and very short limbs. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S6 EP S6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800019 ER PT J AU Hershey, CL Lin, YL Fisher, DE AF Hershey, CL Lin, YL Fisher, DE TI The Microphthalmia-associated transcription factor (Mitf) is required for proper bone development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Kentucky, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S282 EP S282 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801495 ER PT J AU Huang, W Rudkin, G Ishida, K Yamaguchi, DT Miller, TA AF Huang, W Rudkin, G Ishida, K Yamaguchi, DT Miller, TA TI Knockdown of chordin using siRNA induces osteoblastic differentiation in MC3T3-E1 preosteoblastic cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S404 EP S404 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802321 ER PT J AU Inada, M Byrne, MH Kennedy, AM Christie, PT Whyte, MP Thaiker, RV Krane, SM AF Inada, M Byrne, MH Kennedy, AM Christie, PT Whyte, MP Thaiker, RV Krane, SM TI Missouri variant of human spondyloepimetaphyseal dysplasia (SEMDMO) due to matrix metalloproteinase 13 (MMP13) mutation in the pro-domain results in altered secretion and intracellular autoactivation of MMP13 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, CIID, Charlestown, MA USA. Univ Oxford, Nuffield Dept Clin Med, Oxford, England. Shriners Hosp Children, Metab Res Unit, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S63 EP S63 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800243 ER PT J AU Isales, CM Ding, KH Divieti, P Bringhurst, FR AF Isales, CM Ding, KH Divieti, P Bringhurst, FR TI A specific high-affinity carboxy-terminal parathyroid hormone receptor is present in vascular endothelial cells and utilizes a calcium-dependent signaling pathway. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Med Coll Georgia, Augusta, GA 30912 USA. Augusta VA Hosp, Augusta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S338 EP S338 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802049 ER PT J AU Kobayashi, T Lyons, KM McMahon, AP Kronenberg, HM AF Kobayashi, T Lyons, KM McMahon, AP Kronenberg, HM TI BMP signaling regulates chondrocyte differentiation and maturation at multiple steps SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Harvard Univ, Cambridge, MA 02138 USA. RI Lyons, Karen/P-1843-2014 OI Lyons, Karen/0000-0001-9420-5813 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S62 EP S62 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800237 ER PT J AU Krall, EA Fleet, JC Vokonas, PS Miller, DR Rich, SE AF Krall, EA Fleet, JC Vokonas, PS Miller, DR Rich, SE TI Interactions of calcium intake with FokI and androgen receptor genotypes in men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Boston Univ, Boston, MA 02215 USA. Purdue Univ, W Lafayette, IN 47907 USA. VA Boston Healthcare Syst, Boston, MA USA. VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S245 EP S245 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801333 ER PT J AU Leder, BZ Wyland, JJ Neer, RM Hayes, A Hunzelman, J Gibson, K Finkelstein, JS AF Leder, BZ Wyland, JJ Neer, RM Hayes, A Hunzelman, J Gibson, K Finkelstein, JS TI Effects of PTH, alendronate, or both on bone turnover in osteoporotic men SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S44 EP S45 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800173 ER PT J AU Linglart, A Juppner, H Bastepe, M AF Linglart, A Juppner, H Bastepe, M TI Loss-of-function mutations in exons 2 through 13 of GNAS impair signalling through both human Gs-alpha and XL-alpha proteins. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S338 EP S338 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802048 ER PT J AU Linglart, A Juppner, H Bastepe, K AF Linglart, A Juppner, H Bastepe, K TI A novel deletion upstream of GNAS causes a form of autosomal dominant pseudohypoparathyroidism Ib and delineates a region crucial for maintaining exon A/B methylation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S53 EP S53 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800204 ER PT J AU Mulder, JE Sklar, CA Mertens, AC Robison, LL Diller, L Klibanski, A Bilezikian, JP AF Mulder, JE Sklar, CA Mertens, AC Robison, LL Diller, L Klibanski, A Bilezikian, JP TI Estrogen in the establishment of peak bone mass among childhood cancer survivors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Columbia Univ, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Minnesota, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S225 EP S225 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801251 ER PT J AU Napierala, D Morello, R Zhou, G Zhen, O Bertin, T Shivdasani, R Lee, B AF Napierala, D Morello, R Zhou, G Zhen, O Bertin, T Shivdasani, R Lee, B TI Expression of the Trps1 transcription factor and its regulation of Runx2. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S28 EP S29 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800108 ER PT J AU Neer, R Hayes, A Wyland, J Finkelstein, J AF Neer, R Hayes, A Wyland, J Finkelstein, J TI Effects of parathyroid hormone, alendronate, or both on bone density in osteoporotic postmenopausal women. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S98 EP S98 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800382 ER PT J AU Nishimori, S Elmessadi, N Burke, JF Park, D Short, GF Kronenberg, HM AF Nishimori, S Elmessadi, N Burke, JF Park, D Short, GF Kronenberg, HM TI Gene expression within discrete compartments in the growth plate using microarray analysis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Microarray Facil, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S218 EP S219 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801225 ER PT J AU Rao, H Kajiya, H Safran, K Choi, SJ Kurihara, N Anderson, J Roodman, GD AF Rao, H Kajiya, H Safran, K Choi, SJ Kurihara, N Anderson, J Roodman, GD TI alpha(9)beta(1) integrin is expressed on osteoclast precursors and mediates osteoclast formation though its interaction with ADAM8. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S153 EP S153 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800604 ER PT J AU Sabbagh, Y Carpenter, TO Demay, M AF Sabbagh, Y Carpenter, TO Demay, M TI Characterization of growth plate abnormalities in rachitic mouse models. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S349 EP S349 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802099 ER PT J AU Schiller, PC D'Ippolito, G Divieti, P Bringhurst, FR Howard, CA AF Schiller, PC D'Ippolito, G Divieti, P Bringhurst, FR Howard, CA TI Specific activation of type I or C-terminal PTH receptors regulate gap-junctional communication among bone-derived cells expressing or lacking PTH1R. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Miami, VAMC, Miami, FL 33152 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S478 EP S478 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802631 ER PT J AU Selim, A Mahon, MJ Jueppner, H Bringhurst, FR Divieti, P AF Selim, A Mahon, MJ Jueppner, H Bringhurst, FR Divieti, P TI Role of voltage dependent calcium channels in carboxyl-terminal parathyroid hormone receptor signaling. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S194 EP S194 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801121 ER PT J AU Seton, M AF Seton, M TI Paget's disease of bone in a younger cohort: A more subtle disease. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S185 EP S185 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801088 ER PT J AU Shoback, DM Pollina, C Chang, W Pratt, S Hyodo, S Takei, Y Loretz, CA AF Shoback, DM Pollina, C Chang, W Pratt, S Hyodo, S Takei, Y Loretz, CA TI Ca2+-sensing receptor of Mozambique tilapia (tCaR): cDNA expression, signal transduction, and salinity-dependent mRNA expression in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Natl Sci Fdn, Tokyo Reg Off, Tokyo, Japan. Univ Tokyo, Ocean Res Inst, Tokyo 164, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S196 EP S196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801129 ER PT J AU Shoback, DM Arends, RH Roskos, L Shetty, S Wyres, M Huang, S Raie, N Bell, GM AF Shoback, DM Arends, RH Roskos, L Shetty, S Wyres, M Huang, S Raie, N Bell, GM TI Treatment of parathyroid carcinoma with ABX10241, a monoclonal antibody to parathyroid hormone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Abgenix Inc, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S187 EP S187 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801095 ER PT J AU Sitara, D Erben, RG Carr, C Juppner, H Lanske, B AF Sitara, D Erben, RG Carr, C Juppner, H Lanske, B TI Physiological role and expression of Fgf-23 in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Munich, Inst Physiol Physiol Chem & Anim Nutr, Munich, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S35 EP S35 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800134 ER PT J AU Tawfeek, HA Abou-Samra, AB AF Tawfeek, HA Abou-Samra, AB TI A role for Src family kinases in PTH activation of ERK1/2 mitogen activated protein kinases. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S477 EP S477 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802628 ER PT J AU Tsuji, K Bandyopadhyay, A Cox, K Harfe, B Tabin, CJ Rosen, V AF Tsuji, K Bandyopadhyay, A Cox, K Harfe, B Tabin, CJ Rosen, V TI Absence of both BMP2 and BMP4 during skeletal development results in severe defects in osteoblasts but not in chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Dept Tissue Growth & Repair, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. RI Bandyopadhyay, Amitabha/B-9735-2008 NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S11 EP S11 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800038 ER PT J AU Weber, JM Adams, GB Guzman, ML Jordan, CT Scadden, DT Milner, LA Calvi, LM AF Weber, JM Adams, GB Guzman, ML Jordan, CT Scadden, DT Milner, LA Calvi, LM TI Parathyroid hormone treatment improves survival after bone marrow transplantation and increases osteoblastic expression of the Notch ligand Jagged1 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Univ Rochester, Sch Med, Endocrine Unit, Rochester, NY USA. Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Univ Rochester, Sch Med, Wilmot Canc Ctr, Rochester, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S407 EP S407 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326802338 ER PT J AU Wise, LM Jurisicova, A Perez, G Tilly, J Grynpas, MD AF Wise, LM Jurisicova, A Perez, G Tilly, J Grynpas, MD TI The effects of ovariectomy on bone quality of bax-deficient mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S296 EP S296 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801552 ER PT J AU Wu, Y Ackerman, JL Graham, L Glimcher, M AF Wu, Y Ackerman, JL Graham, L Glimcher, M TI MRI mapping of the degree of bone mineralization. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S229 EP S229 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326801268 ER PT J AU Yang, D Guo, J Bringhurst, FR AF Yang, D Guo, J Bringhurst, FR TI PTH (1-34) accelerates osteoblast differentiation via a PLC-independent PKC pathway. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S41 EP S41 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800159 ER PT J AU Yu, X Sabbagh, Y Davis, SI Demay, MB White, KE AF Yu, X Sabbagh, Y Davis, SI Demay, MB White, KE TI Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res C1 Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Yu, Xijie/H-4124-2011 OI Yu, Xijie/0000-0002-3504-7664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2004 VL 19 SU 1 BP S42 EP S42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860FB UT WOS:000224326800163 ER PT J AU Massie, BM AF Massie, BM TI Should the management of heart failure become a new subspecialty? SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID CARDIOLOGISTS; PROGRAM C1 San Francisco VAMC, Cardiol Div 111C, San Francisco, CA 94121 USA. RP Massie, BM (reprint author), San Francisco VAMC, Cardiol Div 111C, 4150 Clement St, San Francisco, CA 94121 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2004 VL 10 IS 5 BP 363 EP 365 DI 10.1016/j.cardfail.2004.08.164 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863VJ UT WOS:000224591200001 PM 15470643 ER PT J AU Masoudi, FA Rumsfeld, JS Havranek, EP House, JA Peterson, ED Krumholz, HM Spertus, JA Spertus, J Tsuyuki, RT Clark, CB Hott, B Havranek, EP Masoudi, FA Rumsfeld, JS Kale, P Williams, RE Heidenreich, PA Peterson, ED McCullough, P Krumholz, H Dunlap, M Goff, D AF Masoudi, FA Rumsfeld, JS Havranek, EP House, JA Peterson, ED Krumholz, HM Spertus, JA Spertus, J Tsuyuki, RT Clark, CB Hott, B Havranek, EP Masoudi, FA Rumsfeld, JS Kale, P Williams, RE Heidenreich, PA Peterson, ED McCullough, P Krumholz, H Dunlap, M Goff, D CA Cardiovascular Outcomes Res TI Age, functional capacity, and health-related quality of life in patients with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; elderly; quality of life; functional status ID CITY CARDIOMYOPATHY QUESTIONNAIRE; CONTROLLED-TRIAL; EXERCISE CAPACITY; CLINICAL-TRIALS; OLDER; DIGOXIN; WITHDRAWAL; OUTCOMES; WALK AB Background: Although heart failure disproportionately affects older persons and is associated with significant physical disability, existing data on physical limitations and health-related quality of life (HRQL) derive largely from studies of younger subjects. We compared the relationship between functional limitation and HRQL between older and younger patients with heart failure. Methods and Results: We evaluated 546 outpatients with heart failure enrolled in a multicenter prospective cohort study. At baseline and 6 2 weeks later, functional status was assessed by New York Heart Association (NYHA) classification and 6-minute walk testing. HRQL was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Comparing older (age >65 years, n = 218) and younger patients (n = 328), we assessed baseline HRQL across strata of functional status. In the 484 patients who completed follow-up (194 older and 290 younger patients), we also assessed the changes in HRQL associated with changes in functional status over time. At baseline, older patients had better HRQL than younger patients (mean KCCQ score 60 +/- 25 versus 54 +/- 28, P = .005) in spite of worse NYHA class (mean 2.54 versus 2.35, P < .001) and lower 6-minute walk distances (824 +/- 378 versus 1064 +/- 371 feet, P < .001). After multivariable adjustment including baseline NYHA class, older age was independently correlated with better HRQL (beta = +7.9 points, P < .001). At follow-up, older patients with a deterioration in NYHA class experienced marked declines in HRQL compared with younger patients (mean HRQL change of - 14.4 points versus +03 points, respectively, P < .001). Analyses using 6-minute walk distance as the functional measure yielded similar results. Conclusions: Although older patients with heart failure have relatively good HRQL in spite of significant functional limitations, they are at risk for worsening HRQL with further decline in functional status. These results underscore the importance of treatments aimed at maintaining functional status in older persons with heart failure, including those with significant baseline functional limitations. C1 Denver Hlth Med Ctr, Div Cardiol MC 0960, Dept Med, Denver, CO 80204 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Denver VA Med Ctr, Dept Med, Denver, CO USA. UMKC, Mid Amer Heart Inst, Kansas City, MO USA. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Masoudi, FA (reprint author), Denver Hlth Med Ctr, Div Cardiol MC 0960, Dept Med, 777 Bannock St, Denver, CO 80204 USA. RI Tsuyuki, Ross/E-2462-2016 OI Tsuyuki, Ross/0000-0002-3724-598X FU NIA NIH HHS [K08-AG01011] NR 32 TC 84 Z9 86 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2004 VL 10 IS 5 BP 368 EP 373 DI 10.1016/j.cardfail.2004.01.009 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863VJ UT WOS:000224591200003 PM 15470645 ER PT J AU Mansour, M Holmvang, G Mela, T Keane, D Ruskin, J AF Mansour, M Holmvang, G Mela, T Keane, D Ruskin, J TI Anterior and posterior right middle pulmonary veins in a patient undergoing catheter ablation for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmanansour@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2004 VL 15 IS 10 BP 1231 EP 1231 DI 10.1046/j.1540-8167.2004.04133.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 865CB UT WOS:000224679000027 PM 15485456 ER PT J AU Taneri, S Feit, R Azar, DT AF Taneri, S Feit, R Azar, DT TI Safety, efficacy, and stability indices of LASEK correction in moderate myopia and astigmatism SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; DIFFUSE LAMELLAR KERATITIS; ASSISTED SUBEPITHELIAL KERATECTOMY; PHOTOREFRACTIVE KERATECTOMY; EPITHELIAL KERATOMILEUSIS; PHOTOTHERAPEUTIC KERATECTOMY; CORNEAL ECTASIA; FOLLOW-UP; LASIK; COMPLICATIONS AB Purpose: To evaluate the visual outcomes and complications in low to moderate levels of myopia and astigmatism treated with laser-assisted subepithelial keratectomy (LASEK) with a focus on postoperative recovery. Setting: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Methods: A retrospective analysis of a case series of eyes treated with LASEK from 1996 to July 2002 with a follow-up of 2 years was performed. The LASEK technique involved creating an epithelial flap with 25 to 45 seconds of exposure to 20% alcohol, ablating the corneal surface using 3 different excimer lasers and nomogram adjustment, and repositioning the flap and applying a bandage contact lens. The main outcome measures were uncorrected visual acuity (UCVA), efficacy index, manifest refraction, best spectacle-corrected visual acuity (BSCVA), safety index, retreatment rate, and complications. Results: One hundred seventy-one eyes (85 right eyes and 86 left eyes) of 105 patients were studied. Preoperatively, the mean spherical equivalent was -2.99 diopters (D) +/- 1.43 (SD) (range -0.38 to -7.75 D) and the mean cylinder, -0.78 +/- 0.73 D. The UCVA ranged from 20/800 to 20/32, and the BSCVA ranged from 20/63 to 20/16; the median was 20/20. One week postoperatively, 96% of eyes had a UCVA of 20/40 or better but definitive visual recovery took more than 4 weeks in some eyes. Approximately 95% of eyes were within +/-1.0 D of emmetropia after 4 to 52 weeks; the remaining 5% did not show major deviations. At 4 to 52 weeks, only 1 eye was overcorrected by more than 1.0 D of manifest refraction. The safety index remained close to 1.0 for the follow-up after 4 weeks. The efficacy index displayed a plateau at 0.9 from 1 month to 1 year. No serious complication (including recurrent erosion syndrome) was encountered. The mean follow-up was 31 weeks, and the retreatment rate was 2.9% up to 2 years of follow-up. Conclusions: The long-term safety and effectiveness of LASEK for the correction of low to moderate myopia and astigmatism were demonstrated. The treatment effect stabilized after 4 weeks. (C) 2004 ASCRS and ESCRS. C1 Massachusetts Eye & Ear Infirm, Corneal Serv, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu OI Taneri, Suphi/0000-0003-0593-6847 NR 49 TC 29 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 2004 VL 30 IS 10 BP 2130 EP 2137 DI 10.1016/j.jcrs.2004.02.070 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 865RB UT WOS:000224719200031 PM 15474826 ER PT J AU Jung, JC West-Mays, JA Stramer, BM Byrne, MH Scott, S Mody, MK Sadow, PM Krane, SM Fini, ME AF Jung, JC West-Mays, JA Stramer, BM Byrne, MH Scott, S Mody, MK Sadow, PM Krane, SM Fini, ME TI Activity and expression of Xenopus laevis matrix metalloproteinases: Identification of a novel role for the hormone prolactin in regulating collagenolysis in both amphibians and mammals SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TADPOLE TAIL REGRESSION; THYROID-HORMONE; CELL-DEATH; GENE-TRANSCRIPTION; RECEPTOR GENES; GROWTH-HORMONE; DNA-BINDING; I COLLAGEN; METAMORPHOSIS; RESORPTION AB Prolactin (PRL) has long been implicated in Xenopus metamorphosis as an anti-metamorphic and/or juvenilizing hormone. Numerous studies showed that PRL could prevent effects of either endogenous or exogenous thyroid hormone (TN;T-3). It has been shown that expression of matrix metalloproteinases (MMPs) is induced by TH during Xenopus metamorphosis. Direct in vivo evidence, however, for such anti-TH effects by PRL with respect to MMPs has not been available for the early phase of Xenopus development or metamorphosis. To understand the functional role of PRL, we investigated effects of PRL on Xenopus collagenase-3 (XCL3) and collagenase-4 (XCL4) expression in a cultured Xenopus laevis cell line, XL-177. Northern blot analysis demonstrated that XCL3 and XCL4 expression were not detected in control or T-3-treated cells, but were differentially induced by PRL in a close- and time-dependent fashion. Moreover, treatment with IL-1alpha as well as phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, or H8, a protein kinase A (PKA) inhibitor, augmented PRL-induced collagenase expression, suggesting that multiple protein kinase pathways and cytokines may participate in PRL-induced collagenase expression. Interestingly, XCL3 expression could be induced in XL-177 cells by T-3, but only when co-cultured with prometamorphic Xenopus tadpole tails (stage 54/55), suggesting that the tails secrete a required intermediate signaling molecule(s) for T-3-induced XCL3 expression. Taken together, these data demonstrate that XCL3 and XCL4 can be differentially induced by PRL and T-3 and further suggest that PRL is a candidate regulator of TH-independent collagenase expression during the organ/tissue remodeling which occurs in Xenopus development. C1 Univ Miami, Sch Med, Evelyn F & William L McKnight Vis Res Ctr, Bascom Palmer Eye Inst, Miami, FL 33136 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Fini, ME (reprint author), Univ Miami, Sch Med, Evelyn F & William L McKnight Vis Res Ctr, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA. EM efini@med.miami.edu FU NEI NIH HHS [EY13078, EY12651]; NIAMS NIH HHS [AR44815] NR 52 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2004 VL 201 IS 1 BP 155 EP 164 DI 10.1002/jcp.20037 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 851RM UT WOS:000223702700015 PM 15281098 ER PT J AU Ayata, C Shin, HK Salomone, S Ozdemir-Gursoy, Y Boas, DA Dunn, AK Moskowitz, MA AF Ayata, C Shin, HK Salomone, S Ozdemir-Gursoy, Y Boas, DA Dunn, AK Moskowitz, MA TI Pronounced hypoperfusion during spreading depression in mouse cortex SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE laser speckle flowmetry; laser Doppler flowmetry; optical imaging; cortical spreading depression; nitric oxide ID CEREBRAL-BLOOD-FLOW; OXIDE SYNTHASE INHIBITION; RAT-BRAIN CORTEX; NITRIC-OXIDE; ARTERY OCCLUSION; ARTERIOLAR DILATION; EXTRACELLULAR K+; POTASSIUM; ISCHEMIA; MECHANISMS AB We studied unique cerebral blood flow (CBF) responses to cortical spreading depression in mice using a novel two-dimensional CBF imaging technique, laser speckle flowmetry. Cortical spreading depression caused a triphasic CBF response in both rat and mouse cortex. In rats, mild initial hypoperfusion (approximately 75% of baseline) was followed by a transient hyperemia reaching approximately 220% of baseline. In mice, the initial hypoperfusion was pronounced (40-50% of baseline), and the anticipated hyperemic phase barely reached baseline. The duration of hypoperfusion significantly correlated with the duration of the DC shift. As a possible explanation for the pronounced hypoperfusion, mouse cerebral vessels showed enhanced resistance to relaxation by acetylcholine (3 muM) after K+-induced preconstriction (20, 40, and 80 mM) but dilated normally in response to acetylcholine after preconstriction with U46619, a synthetic thromboxane A2 analog. By contrast, rat vessels dilated readily to acetylcholine after preconstriction by K+. The transient normalization of CBF after hypoperfusion in the mouse was abolished by L-NA but not 7-NI. In summary, the CBF response to cortical spreading depression in mice contrasts with the rat in that the initial hypoperfusion is pronounced, and the hyperemic phase is markedly diminished. The differences in CBF response between species may be in part caused by an increased sensitivity of mouse cerebral vessels to elevated extracellular K+. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv & Neurosci Intens Care unit,Dept Neur, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014; OI Salomone, Salvatore/0000-0001-5307-6103 FU NIBIB NIH HHS [R01EB00790-01A2]; NINDS NIH HHS [K25NS041291, P01 NS35611, P50 NS10828] NR 51 TC 96 Z9 98 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2004 VL 24 IS 10 BP 1172 EP 1182 DI 10.1097/01.WCB.0000137057.92786.F3 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 859YP UT WOS:000224304600012 PM 15529018 ER PT J AU Herbert, MR AF Herbert, MR TI Neurointaging in disorders of social and emotional functioning: What is the question? SO JOURNAL OF CHILD NEUROLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDER; CEREBRAL WHITE-MATTER; CORPUS-CALLOSUM SIZE; HUMAN NEURAL SYSTEMS; MAGNETIC-RESONANCE; CHILDHOOD AUTISM; INFANTILE-AUTISM; HEAD CIRCUMFERENCE AB Social and emotional processing uses neural systems involving structures ranging from the brain stem to the associational cortex. Neuroimaging research has attempted to identify abnormalities in components of these systems that would underlie the behavioral abnormalities seen in disorders of social and emotional processing, notably autism spectrum disorders, the focus of this review. However, the findings have been variable. The most replicated anatomic finding (a tendency toward large brains) is not modular, and metabolic imaging and functional imaging (although showing substantial atypicality in activation) are not consistent regarding specific anatomic sites. Moreover, autism spectrum disorder demonstrates substantial heterogeneity on multiple levels. Here evidence is marshaled from a review of neuroiniaging data to support the claim that abnormalities in social and emotional processing on the autism spectrum are a consequence of systems disruptions in which the behaviors are a final common pathway and the focal findings can be variable, downstream of other pathogenetic mechanisms, and downstream of more pervasive abnormalities. (J Child Neurol 2004; 19:772-784). C1 Harvard Univ, Massachusetts Gen Hosp East, Div Pediat Neurol,Dept Neurol, Ctr Morphometr Anal,Neurosci Ctr,Med Sch, Charlestown, MA 02129 USA. RP Herbert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Div Pediat Neurol,Dept Neurol, Ctr Morphometr Anal,Neurosci Ctr,Med Sch, 149 13th St Room 6012, Charlestown, MA 02129 USA. EM mherbert1@partners.org FU NINDS NIH HHS [NS02126] NR 190 TC 12 Z9 12 U1 8 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 2004 VL 19 IS 10 BP 772 EP 784 PG 13 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 920PT UT WOS:000228703300007 PM 15559893 ER PT J AU Castellon, SA Ganz, PA Bower, JE Petersen, L Abraham, L Greendale, GA AF Castellon, SA Ganz, PA Bower, JE Petersen, L Abraham, L Greendale, GA TI Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID CEREBRAL-BLOOD-FLOW; QUALITY-OF-LIFE; COGNITIVE FUNCTION; LONG-TERM; ESTROGEN; WOMEN; BRAIN; THERAPY; DYSFUNCTION; REPLACEMENT AB The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors (BCS) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy. The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer, a group not included in the majority of previous cognitive functioning studies. We also sought to explore whether usage of the anti-estrogen drug tamoxifen, a common component of breast cancer treatment, was related to neurocognitive functioning. Finally, we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS. Fifty-three survivors of breast cancer (all between 2-5 years after diagnosis and initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery, and measures of mood, energy level, and self-reported cognitive functioning. Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning, vistiospatial functioning, and visual memory than BCS treated with surgery only. Those who received both chemotherapy and tamoxifen showed the greatest compromise. Although patients who received chemotherapy (with and without tamoxifen) performed worse than those treated with surgery only on several domains, neither group was significantly different from demographically matched comparison subjects without a history of breast cancer. Finally, we found no relationship between subjective cognitive complaints and objective performance, although cognitive complaints were associated with measures of psychological distress and fatigue. We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy, especially in combination with tamoxifen, can have adverse yet subtle effects on cognitive functioning. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Mental Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Geriatr Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA. RP Castellon, SA (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Sch Med, 760 Westwood Plaza,C8-747, Los Angeles, CA 90024 USA. EM scastell@ucla.edu NR 53 TC 218 Z9 222 U1 1 U2 10 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 2004 VL 26 IS 7 BP 955 EP 969 DI 10.1080/13803390490510905 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 876ZF UT WOS:000225536900008 PM 15742545 ER PT J AU Misra, M Miller, KK Almazan, C Ramaswamy, K Lapcharoensap, W Worley, M Neubauer, G Herzog, DB Klibanski, A AF Misra, M Miller, KK Almazan, C Ramaswamy, K Lapcharoensap, W Worley, M Neubauer, G Herzog, DB Klibanski, A TI Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; GROWTH-HORMONE; MINERAL DENSITY; GLUCOSE-TOLERANCE; GLUCOCORTICOID-RECEPTORS; APPROXIMATE ENTROPY; CUSHINGS-DISEASE; WEIGHT-GAIN; WOMEN; MASS AB Anorexia nervosa ( AN) is associated with low bone density in adolescents and adults. Hypercortisolemia has been reported in adults with this disorder and has been hypothesized to be a factor in bone loss. However, the secretory dynamics of cortisol in adolescents with AN and the contribution of alterations in cortisol secretion to bone metabolism in AN have not been examined. We examined the dynamics of cortisol secretion by Cluster and deconvolutional analysis in 23 girls with AN and 21 healthy adolescents of comparable age and maturity. Cortisol sampling was performed every 30 min for 12 h overnight. Twenty-four-hour urinary free cortisol (UFC) and creatinine (cr) were obtained for all subjects. The surface area ( SA) of the subjects was calculated. Markers of bone turnover ( type 1 procollagen, osteocalcin, and N-telopeptide) were examined. Subjects with AN were prospectively followed over 1 yr, and those who recovered weight ( defined as a 10% increase in body mass index) were again studied. On Cluster analysis, girls with AN had significantly higher mean cortisol (8.6 +/- 2.0 vs. 5.9 +/- 1.1 mug/dl; P < 0.0001), nadir cortisol (5.5 +/- 2.3 vs. 3.4 +/- 1.2 mu g/dl; P = 0.0008), valley mean cortisol (7.0 +/- 2.7 vs. 4.7 +/- 1.5 mu g/dl; P = 0.001), peak amplitude (12.6 +/- 4.4 vs. 7.8 +/- 3.0 mu g/dl; P = 0.0004), peak area (652 +/- 501 vs. 340 +/- 238 mu g/dl; P = 0.02), and total area under the curve (6112 +/- 1467 vs. 4117 +/- 802 mu g/dl; P < 0.0001) than healthy adolescents. On deconvolutional analysis, the frequency of nocturnal secretory bursts ( 7.0 +/- 1.2 vs. 5.8 +/- 1.3/12 h; P = 0.001), total nocturnal pulsatile cortisol secretion (69.3 +/- 14.7 vs. 53.9 +/- 11.1 mug/dl; P = 0.0003), and total cortisol secretion (89.6 +/- 18.8 vs. 71.2 +/- 17.6 mug/dl; P = 0.002) were significantly higher in girls with AN than in healthy controls. Cortisol half-life trended higher in girls with AN. However, basal cortisol secretion and approximate entropy did not differ between the groups. UFC/cr and UFC/cr. SA were significantly higher in girls with AN than in controls [0.050 +/- 0.028 vs. 0.036 +/- 0.017 ( P = 0.04) and 0.035 +/- 0.020 vs. 0.023 +/- 0.012 ( P = 0.03)]. Six of 23 girls with AN had UFC/cr. SA values that were more than 2 SD above those in healthy controls. An inverse correlation was noted between measures of cortisol concentration as well as pulsatile secretion and measures of nutritional status ( body mass index, fat mass, leptin, insulin, and IGF-I). An oral glucose load suppressed cortisol levels in healthy adolescents, but not in AN patients. Weight recovery was associated with a significant decrease in the number of secretory bursts. In girls with AN, strong inverse correlations were noted between levels of cortisol ( mean, nadir, and total area under the curve) and levels of markers of bone formation (C-terminal propeptide of type 1 procollagen and osteocalcin). Conversely, in healthy controls, cortisol values did not predict levels of markers of bone turnover. Adolescent girls with AN have significantly higher serum cortisol concentrations and UFC/cr. SA values than healthy adolescents. This increased cortisol concentration is a function of increased frequency of secretory bursts, resulting in increased pulsatile secretion. Hypercortisolemia appears to be a direct consequence of undernutrition and is associated with a decrease in markers of bone formation. Therefore, high cortisol values in AN may contribute to the low bone density observed in adolescents with this disorder by decreasing bone formation. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Core Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [K23-RR-018851, M01-RR-01066]; NIDDK NIH HHS [DK-062249] NR 54 TC 104 Z9 104 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2004 VL 89 IS 10 BP 4972 EP 4980 DI 10.1210/jc.2004-0723 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860EW UT WOS:000224326300030 PM 15472193 ER PT J AU Schneyer, AL Wang, QF Sidis, Y Sluss, PM AF Schneyer, AL Wang, QF Sidis, Y Sluss, PM TI Differential distribution of follistatin isoforms: Application of a new FS315-specific immunoassay SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 28-31, 2002 CL Baltimore, MD SP Soc Study Reprod ID ACTIVIN-BINDING PROTEIN; CELL-LINE PA-1; FOLLICULAR-FLUID; HUMAN SERUM; HORMONE CONCENTRATIONS; GRANULOSA-CELL; INHIBIN; IDENTIFICATION; PROTEOGLYCANS; LOCALIZATION AB Follistatin (FST) is a monomeric activin-binding and neutralization protein that has at least three isoforms in human tissues and fluids. The full-length FS315 protein has an acidic 26-residue C-terminal tail that is not present in the shortest form, FS288, due to alternative splicing. An intermediate form, FS303, was identified in follicular fluid that is presumably derived by proteolytic processing of this tail domain. Interestingly, the biochemistry of each of these three isoforms is distinct, including their ability to bind to cell surface proteoglycans, an activity that ranks in the order FS288 > FS303 > FS315. This would suggest that the soluble, circulating FST isoform is likely to be FS315, a hypothesis supported by previous determinations that the serum and follicular fluid forms of FST are biochemically distinct. To test this hypothesis, we developed an immunoassay that is specific for full-length FS315. This assay was validated for use with human serum and follicular fluid samples and then used to examine FST in these fluid compartments. Our results indicate that FS315 is indeed the major circulating FST isoform but is undetectable in follicular fluid samples aspirated from normal women or women with polycystic ovary syndrome. These observations confirm the compartmentalization of FST isoforms according to their biochemical properties and biological actions so that the most soluble form is found in the circulation, whereas the forms that bind to cell surface proteoglycans are found in tissue compartments such as the ovarian follicle. They also confirm that the source of FST in human serum is not the ovarian follicle. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Immunodiagnost Lab, Boston, MA 02114 USA. RP Sluss, PM (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Immunodiagnost Lab, Bulfinch Bldg,Suite 051, Boston, MA 02114 USA. EM sluss.patrick@mgh.harvard.edu FU NICHD NIH HHS [HD29364]; NIDDK NIH HHS [DK55838] NR 31 TC 35 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2004 VL 89 IS 10 BP 5067 EP 5075 DI 10.1210/jc.2004-0162 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 860EW UT WOS:000224326300044 PM 15472207 ER PT J AU Doyle, PJ McNeil, MR Mikolic, JM Prieto, L Hula, WD Lustig, AP Ross, K Wambaugh, JL Gonzalez-Rothi, LJ Elman, RJ AF Doyle, PJ McNeil, MR Mikolic, JM Prieto, L Hula, WD Lustig, AP Ross, K Wambaugh, JL Gonzalez-Rothi, LJ Elman, RJ TI The Burden of Stroke Scale (BOSS) provides valid and reliable score estimates of functioning and well-being in stroke survivors with and without communication disorders SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Burden of Stroke Scale (BOSS); stroke; communication disorders; psychometrics; health status ID QUALITY-OF-LIFE; HEALTH SURVEY SF-36; REHABILITATION OUTCOMES; NEGATIVE AFFECT; DISABILITY; INDEPENDENCE; TRIALS AB Background and Objective: This study describes the conceptual foundation and psychometric properties of the Burden of Stroke Scale (BOSS), a patient-reported health status assessment designed to quantify the physical, cognitive, and psychological burden of stroke. Methods: Qualitative research methods were used to develop a 112-item pilot version of the instrument. The pilot version was administered to healthy controls (n = 251) and stroke survivors with (n = 135) and without (n = 146) communication disorders on a single occasion for the purposes of reducing the global item pool, describing the resulting scale properties, examining the dimensionality of the burden of stroke construct, and examining the known-groups validity of the instrument. Results: Sixty-four items were retained, comprising 12 internally consistent and unidimensional scales. Principal components analysis revealed three second-order factors (Physical Activity Limitations, Cognitive Activity Limitations, and Psychological Distress) comprising the Burden of Stroke construct. Comparisons between groups revealed that stroke survivors reported greater activity limitations and psychological distress on all scales relative to controls, and that stroke survivors with communication disorders reported greater activity limitations on swallowing, communication, cognition, and social relations scales relative to non-communicatively disordered stroke survivors. Conclusion: These findings support the internal consistency of the BOSS scales, the hypothesized dimensionality of the burden of stroke construct, and the known-groups validity of the instrument. (C) 2004 Elsevier Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. Eli Lilly & Co, Hlth Outcomes Res Unit, Madrid, Spain. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. Carl T Hayden VA Med Ctr, Phoenix, AZ USA. VA Med Ctr, Salt Lake City, UT USA. VA RR&D Brain Rehabil Res Ctr, Gainesville, FL USA. Aphasia Ctr Calif, Oakland, CA USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM patrick.doyle@med.va.gov NR 55 TC 40 Z9 43 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2004 VL 57 IS 10 BP 997 EP 1007 DI 10.1016/j.jclinepi.2003.11.016 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 873JP UT WOS:000225276100001 PM 15528050 ER PT J AU Cotter, DJ Stefanik, K Zhang, Y Thamer, M Scharfstein, D Kaufman, J AF Cotter, DJ Stefanik, K Zhang, Y Thamer, M Scharfstein, D Kaufman, J TI Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE end point; surrogate; outcome assessment; causal effect; anemia; management of; epoetin; survival; hematocrit; target ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; STAGE RENAL-DISEASE; CLINICAL-TRIALS; OUTCOME MEASURES; MORTALITY; HEMOGLOBIN; ANEMIA; DIALYSIS; PREDICTORS; ADEQUACY AB Objective: To evaluate the use of hematocrit as a surrogate end point for survival among end-stage renal disease (ESRD) patients treated with epoetin. Study design and setting: Using United States Renal Data System (USRDS) data, we conducted an observational prospective study to analyze the relationships among epoetin dose, hematocrit, and survival for 31,301 facility-based hemodialysis patients incident to ESRD therapy in 1998. To address our objective, we used criteria developed by Prentice based on results from a Cox regression model. Results: Results indicate that hematocrit is inversely associated with epoetin dose. For the same epoetin treatment-related achieved hematocrit levels, there were widely varying treatment-related survival outcomes, thereby challenging a central criterion required to empirically validate a surrogate end point. Conclusion: Our results support earlier clinical trial and epidemiological data suggesting that hematocrit may not be a valid surrogate for survival among the epoetin-treated renal failure population. We hypothesize that hematocrit may not be in the causal pathway or that epoetin may have important mechanisms of action apart from increasing hematocrit. Effective treatment for anemia may therefore not be simply a matter of increasing hematocrit. This study has potential implications for revising the existing treatment guidelines for anemia management and selecting an appropriate treatment regimen. (C) 2004 Elsevier Inc. All rights reserved. C1 Med Technol & Practice Patterns Inst Inc, Bethesda, MD 20814 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. RP Cotter, DJ (reprint author), Med Technol & Practice Patterns Inst Inc, 4733 Bethesda Ave,Suite 510, Bethesda, MD 20814 USA. EM dcott@mtppi.org NR 45 TC 41 Z9 42 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2004 VL 57 IS 10 BP 1086 EP 1095 DI 10.1016/j.jclinepi.2004.05.002 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 873JP UT WOS:000225276100011 PM 15528060 ER PT J AU Grossberg, R Zhang, YW Gross, R AF Grossberg, R Zhang, YW Gross, R TI A time-to-prescription-refill measure of antiretroviral adherence predicted changes in viral load in HIV SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE adherence; HIV-1; antiretroviral therapy; measurement; validity; viral load ID PROTEASE INHIBITORS; DRUG-RESISTANCE; THERAPY; INFECTION AB Objective: The goal of this study was to determine the validity and utility of a pharmacy-based time-to-refill measure of antiretroviral therapy adherence. Methods: We performed an observational cohort study of 110 HIV-infected subjects on a stable, highly active antiretroviral regimen for at least 3 months at a Veterans' Affairs Medical Center in Philadelphia, Pennsylvania. Results: The viral load decreased by 0.12 log c/mL (95% confidence interval [CI] 0.01-0.23 log c/mL) for each 10% increase in pharmacy-based time-to-refill defined adherence as compared with 0.05 log c/mL (95% CI -0.14-0.25 log c/mL) for the self-reported adherence measure. Thus, only the refill-defined measure was statistically significantly associated with viral load change. When adherence was classified as good (greater than or equal to85%) versus poor (<85%), both measures demonstrated a significant difference in outcome between groups. Yet, in individuals self-reporting 100% adherence, those classified as good adherers using the pharmacy-based measure had greater viral load reductions than poor adherers (2.4 log c/mL [interquartile range 1.4-3.4] vs. 1.5 log c/mL [interquartile range 0.8-2.4, P = .03). Conclusions: The pharmacy-based technique is a valid measure of antiretroviral therapy adherence. Because it provides clinically relevant information in subjects who self-report 100% adherence, it should be incorporated into clinical practice and adherence research. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Gross, R (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, 804 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rgross@cceb.med.upenn.edu FU AHRQ HHS [HS10399]; NIAID NIH HHS [P30-AI45008, U01-AI32783]; NIMH NIH HHS [K08 MH01584] NR 14 TC 103 Z9 106 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2004 VL 57 IS 10 BP 1107 EP 1110 DI 10.1016/j.jclinepi.2004.04.002 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 873JP UT WOS:000225276100014 PM 15528063 ER PT J AU Gralnek, IM Hays, RD Kilbourne, AM Chang, L Mayer, EA AF Gralnek, IM Hays, RD Kilbourne, AM Chang, L Mayer, EA TI Racial differences in the impact of irritable bowel syndrome on health-related quality of life SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GA SP Amer Gastroenterol Assoc DE health-related quality of life; functional status; irritable bowel syndrome; functional bowel disease ID NON-HISPANIC WHITES; CLINICAL-TRIALS; UNITED-STATES; GASTROINTESTINAL SYMPTOMS; MEDICAL OUTCOMES; PATIENT OUTCOMES; SURVEY SF-36; DISEASE; CARE; PREVALENCE AB Goals: To compare the impact of irritable bowel syndrome (IBS) on health related quality of life (HRQOI) for non-white and white IBS patients. Background: There are no reported data evaluating the HRQOL of non-white persons with IBS. Study: SF-36 scores are compared between non-white IBS patients (n = 166), white IBS patients (n = 707), the general US population, and patients with selected chronic diseases. Results: Of the n = 166 non-white IBS patients included for analysis, 66 (40%) described themselves as African-American, 56 (34%) as Hispanic, 25 (15%) as Asian-American, 2 (1%) as Native American and the remaining 17 (10%) as "other." Compared with white IBS patients, non-white IBS patients reported similar decrements in their HRQOL after controlling for age, gender, income and education level. On all 8 SF-36 scales, non-white IBS patients had significantly worse HRQOL compared with the general US population, (P < 0.001). Compared with GERD patients, non-white IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, non-white IBS patients had significantly worse HRQOL on selected SF-36 scales compared with diabetes mellitus and ESRD patients. Non-white IBS patients had significantly better emotional well-being than depressed patients, (P < 0.001). Conclusions: Non-white IBS patients experience impairment in vitality, role limitations-physical, and bodily pain. Yet overall, non-white IBS patients report similar HRQOL to white IBS patients. These data provide the first detailed evaluation of the impact of IBS on HRQOL in non-white IBS patients. C1 CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med,Div Digest Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Study Digest Hlth Care Qual & Outcomes, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med,Div Gen Internal Med Hlth Serv Res, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. RP Gralnek, IM (reprint author), CURE, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM igralnek@mednet.ucla.edu RI Hays, Ronald/D-5629-2013 FU NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 51 TC 15 Z9 16 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2004 VL 38 IS 9 BP 782 EP 789 DI 10.1097/01.mcg.0000140190.65405.fb PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856KZ UT WOS:000224045400012 PM 15365405 ER PT J AU Tian, CR Bagley, J Cretin, N Seth, N Wucherpfennig, KW Iacomini, J AF Tian, CR Bagley, J Cretin, N Seth, N Wucherpfennig, KW Iacomini, J TI Prevention of type 1 diabetes by gene therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MHC CLASS-II; MAJOR HISTOCOMPATIBILITY COMPLEX; INTERFERON-GAMMA RECEPTOR/IGG1; ISLET-CELL TRANSPLANTATION; NOD MICE; T-CELLS; DENDRITIC CELLS; POSITIVE SELECTION; AUTOIMMUNE INSULITIS; HEMATOPOIETIC-CELLS AB The autoimmune disease type 1 diabetes in humans and NOD mice is determined by multiple genetic factors, among the strongest of which is the inheritance of diabetes-permissive MHC class II alleles associated with susceptibility to disease. Here we examined whether expression of MHC class II alleles associated with resistance to disease could be used to prevent the occurrence of diabetes. Expression of diabetes-resistant MHC class II I-Abeta chain molecules in NOD mice following retroviral transduction of autologous bone marrow hematopoietic stem cells prevented the development of autoreactive T cells by intrathymic deletion and protected the mice from the development of insulitis and diabetes. These data suggest that type 1 diabetes could be prevented in individuals expressing MHC alleles associated with susceptibility to disease by restoration of protective MHC class II expression through genetic engineering of hematopoietic stem cells. C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, 149-5210,13th St, Boston, MA 02129 USA. EM joh.iacomini@tbrc.mgh.harvard.edu FU NIAID NIH HHS [R01 AI44268, R01 AI044268, R01 AI043619, R01 AI43619] NR 72 TC 57 Z9 64 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2004 VL 114 IS 7 BP 969 EP 978 DI 10.1172/JCI22103 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 858WT UT WOS:000224223800018 PM 15467836 ER PT J AU Kahn, CR Roth, J AF Kahn, CR Roth, J TI Berson, Yalow, and the JCI: the agony and the ecstasy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN-LIKE ACTIVITY; PLASMA INSULIN; ADIPOSE TISSUE; HUMAN-SERUM; RESISTANCE; ASSAY; OBESITY; HYPOGLYCEMIA; SPECIFICITY; MECHANISMS AB The isolation of insulin in 1921 by Banting, Best, Collip, and Macleod stands as one of the most dramatic stories in modern medical investigation. Only two years passed between the initial experiments in dogs to widespread human application to the awarding of the Nobel Prize in 1923. Insulin-related research has also served as a focus, at least in part, for the work of three other Nobel Prize recipients: determination of the chemical structure of insulin by Frederick Sanger in 1958; determination of the three-dimensional structures of insulin and vitamin B12 by Dorothy Hodgkin in 1964; and finally, the development of immunoassay by Solomon Berson and Rosalyn Yalow in 1959-1960, which led to a Nobel Prize for Yalow in 1977 (five years after the untimely death of Berson). The history of Yalow and Berson's discovery and its impact on the field is an illustration of the adage that every story has two sides. C1 N Shore Long Isl Jewish Hlth Syst, Med Res Inst, New York, NY 11040 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Albert Einstein Coll Med, New York, NY USA. RP Roth, J (reprint author), N Shore Long Isl Jewish Hlth Syst, Med Res Inst, 400 Lakeville Rd,Suite 220,New Hyde Pk, New York, NY 11040 USA. EM c.ronald.kahn@joslin.harvard.edu; jesserothmd@hotmail.com NR 26 TC 10 Z9 10 U1 3 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2004 VL 114 IS 8 BP 1051 EP 1054 DI 10.1172/JCI20042316 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 863CJ UT WOS:000224537700010 PM 15489951 ER PT J AU Mattos-Graner, RO Napimoga, MH Fukushima, K Duncan, MJ Smith, DJ AF Mattos-Graner, RO Napimoga, MH Fukushima, K Duncan, MJ Smith, DJ TI Comparative analysis of Gtf isozyme production and diversity in isolates of Streptococcus mutans with different biofilm growth phenotypes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ORAL IMMUNIZATION; SEQUENCE-ANALYSIS; GLUCOSYLTRANSFERASE; GENES; STRAINS; CHILDREN; POLYMORPHISM; RESPONSES; SURFACES AB Streptococcus mutans is the main pathogenic agent of dental caries. Glucosyltransferases (Gtfs) produced by these bacteria are important virulence factors because they catalyze the extracellular synthesis of glucans that are necessary for bacterial accumulation in the dental biofilm. The diversity of GtfB and GtfC isozymes was analyzed in 44 genotypes of S. mutans that showed a range of abilities to form biofilms in vitro. Several approaches were used to characterize these isozymes, including restriction fragment length polymorphism analysis of the gtfB and gtfC genes, zymographic analysis of the identified GtfB and GtfC genotypes, and quantitation of isozyme production in immunoblot experiments with specific monoclonal antibodies. A high diversity of gtf genes, patterns of enzymatic activity, and isozyme production was identified among the isolates tested. GtfC and, to a lesser extent, GtfB were produced in significantly higher amounts by strains that had high biofilm-forming ability than by strains with low biofilm-forming ability. Biofilm formation was independent of the GtfB and GtfC genotype. Atypical strains that showed an apparent single Gtf isozyme of intermediate size between GtfB and GtfC were also identified. The results indicate that various expression levels of GtfB and GtfC isozymes are associated with the ability of distinct S. mutans genotypes to grow as biofilms, strengthening the results of previous genetic and biochemical studies performed with laboratory strains. These studies also emphasize the need to identify factors that control gtf gene expression. C1 UNICAMP, Fac Odontol, Dept Microbiol & Immunol, BR-13414018 Piracicaba, SP, Brazil. Nihon Univ, Sch Dent, Dept Microbiol, Chiba, Japan. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. RP Mattos-Graner, RO (reprint author), UNICAMP, Fac Odontol, Dept Microbiol & Immunol, Av Limeira 901, BR-13414018 Piracicaba, SP, Brazil. EM rmgraner@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012; Napimoga, Marcelo/F-8789-2011 OI Mattos-Graner, Renata/0000-0001-8309-8135; Napimoga, Marcelo/0000-0003-4472-365X FU NIDCR NIH HHS [R37 DE-06153, R37 DE006153] NR 29 TC 36 Z9 40 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2004 VL 42 IS 10 BP 4586 EP 4592 DI 10.1128/JCM.42.10.4586-4592.2004 PG 7 WC Microbiology SC Microbiology GA 862EM UT WOS:000224473000026 PM 15472313 ER PT J AU Lippman, SM Levin, B Brenner, DE Gordon, GB Aldige, CR Kramer, BS Garber, JE Hawk, E Ganz, PA Somerfield, MR AF Lippman, SM Levin, B Brenner, DE Gordon, GB Aldige, CR Kramer, BS Garber, JE Hawk, E Ganz, PA Somerfield, MR CA ASCO Canc Prevention Comm TI Cancer prevention and the American Society of Clinical Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Canc Prevent & Res Fdn, Alexandria, VA USA. NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. RP Lippman, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2004 VL 22 IS 19 BP 3848 EP 3851 DI 10.1200/JCO.2004.07.139 PG 4 WC Oncology SC Oncology GA 859PY UT WOS:000224281600004 PM 15353541 ER PT J AU Haffajee, AD Uzel, NG Arguello, EI Torresyap, G Guerrero, DM Socransky, SS AF Haffajee, AD Uzel, NG Arguello, EI Torresyap, G Guerrero, DM Socransky, SS TI Clinical and microbiological changes associated with the use of combined antimicrobial therapies to treat "refractory" periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE attachment level; periodontal diseases; pocket depth; "refractory" periodontitis; subgingival microbiota; treatment ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; METRONIDAZOLE PLUS AMOXICILLIN; CREVICULAR FLUID; DISEASE; COMBINATION; PARAMETERS; FEATURES; FIBERS; PLAQUE AB Background: The present investigation examined clinical and microbial changes after a combined aggressive antimicrobial therapy in subjects identified as "refractory" to conventional periodontal therapy. Method: Fourteen subjects were identified as "refractory" based on full-mouth mean attachment loss and/or >3 sites with attachment loss greater than or equal to3 mm following scaling and root planing (SRP), periodontal surgery and systemic antibiotics. After baseline monitoring, subjects received SRP, locally delivered tetracycline at pockets greater than or equal to4 mm, systemically administered amoxicillin (500 mg, t.i.d. for 14 days)+metronidazole (250 mg, t.i.d. for 14 days) and professional removal of supragingival plaque weekly for 3 months. Subjects were monitored clinically every 3 months post-therapy for 2 years. Subgingival plaque samples were taken at the same time points from the mesial aspect of each tooth and the levels of 40 subgingival taxa were determined using checkerboard DNA-DNA hybridization. Mean levels of each species were averaged within a subject at each visit. Significance of changes in clinical and microbiological parameters over time were evaluated using the Friedman or Wilcoxon signed ranks test. Results: On average, subjects showed significant improvements in all clinical parameters after therapy. Mean (+/-SEM) full-mouth pocket depth reduction was 0.83+/-0.13 mm and mean attachment level "gain" was 0.44+/-0.12 at 24 months. Clinical improvement was accompanied by major reductions in multiple subgingival species during the first 3 months of active therapy that were maintained for most species to the last monitoring visit. Reductions occurred for three Actinomyces species, "orange complex" species including Campylobacter showae, Eubacterium nodatum, three Fusobacterium nucleatum subspecies, Peptostreptococcus micros, Prevotella intermedia as well as the "Streptococcus milleri" group, Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedus. Subjects differed in their response to therapy; six modest response subjects exhibited less attachment level gain and were characterized by reductions in the microbiota from baseline to 3 months, but re-growth of many species thereafter. Conclusions: The combined antibacterial therapy was successful in controlling disease progression in 14 "refractory" periodontitis subjects for 2 years. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU NIDCR NIH HHS [DE-10977, DE-12108, DE-12861, DE-13232] NR 30 TC 33 Z9 37 U1 0 U2 7 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2004 VL 31 IS 10 BP 869 EP 877 DI 10.1111/j.1600-051X.2004.00573.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 853WZ UT WOS:000223862400010 PM 15367191 ER PT J AU Wilens, TE Dodson, W AF Wilens, TE Dodson, W TI A clinical perspective of attention-deficit/hyperactivity disorder into adulthood SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Attention Deficit and Hyperactivity Disorder - From Neurobiology to a Plan for Life CY OCT 28-31, 2002 CL Las Vegas, NV ID DEFICIT-HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; SUBSTANCE USE DISORDERS; FOLLOW-UP; CONDUCT DISORDER; PSYCHIATRIC STATUS; TOURETTES-SYNDROME; BIPOLAR DISORDER; METHYLPHENIDATE TREATMENT; DOPAMINE TRANSPORTER AB Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder that affects all age groups. Recent data on the clinical presentation, comorbidity, neuroblology, and treatment are reviewed. Method: Using the search term ADHD, a selective PubMed review of the clinical literature was undertaken to evaluate recent data relevant to ADHD with attention to a life span perspective of the disorder. Results: A growing literature indicates that ADHD is more persistent than previously thought and has a developmental variability in its presentation. The disorder impairs academic, social, and occupational functioning and is often associated with comorbidity, including cigarette smoking and substance abuse. Considerable evidence suggests that the disorder has a strong genetic component and a biological underpinning; the pathophysiology includes dysfunction in both noradrenergic and dopaminergic systems. Both psychosocial therapy and pharmacotherapy have been shown effective in the treatment of the disorder throughout the life span. The therapeutic effectiveness of pharmacologic agents in the treatment of ADHD has been attributed to noradrenergic and/or dopaminergic effects. Conclusion: ADHD is associated with impairment and comorbidity throughout the life span. Growing evidence suggests the importance of short- and long-term management of the disorder. While the long-term treatment of ADHD is expected to lessen the individual's impairment, the outcome for adults who have received treatment since childhood requires further study. C1 Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, 15 Parkman St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [DA 14419] NR 134 TC 131 Z9 134 U1 8 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2004 VL 65 IS 10 BP 1301 EP 1313 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 864SR UT WOS:000224653700002 PM 15491232 ER PT J AU Chinman, M Young, AS Schell, T Hassell, J Mintz, J AF Chinman, M Young, AS Schell, T Hassell, J Mintz, J TI Computer-assisted self-assessment in persons with severe mental illness SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID WORLD-WIDE-WEB; RISK BEHAVIORS; HIV-INFECTION; INFORMATION-SYSTEMS; QUALITY ASSURANCE; RANDOMIZED TRIAL; PATIENT OUTCOMES; SEXUAL-BEHAVIOR; DRUG-USE; SCHIZOPHRENIA AB Background: It has been difficult to improve care for severe mental illness (SMI) in usual care settings because clinical information is not reliably and efficiently managed. Methods are needed for efficiently collecting this information to evaluate and improve health care quality. Audio computer-assisted self-interviewing (ACASI) can facilitate this data collection and has improved outcomes for a number of disorders, suggesting the need to test its accuracy and reliability in people with SMI. Method: Ninety patients with DSM-IV schizophrenia or schizoaffective disorder (N = 45) or bipolar disorder (N = 45) recruited between Oct. 15, 2002, and July 1, 2003, were randomly assigned to 1 of 2 study groups and completed 2 standardized symptom surveys (Revised Behavior and Symptom Identification Scale and the symptom severity scale of the Schizophrenia Outcomes Module 2) 20 minutes apart in a crossover study design. Half of the patients first completed the scales via an in-person interview, and the other half first completed the scales via an ACASI survey self-administered through an Internet browser using a touchscreen developed to meet the cognitive needs of people with SMI. We evaluated attitudes toward ACASI, understanding of the ACASI survey, internal consistency, correlations between the ACASI and interview modes, concurrent validity, and a possible administration mode bias. Results: All ACASI and in-person interview scales had similar internal reliability, high correlations (r = 0.78-1.00), and mean scores similar enough as not to be different at p < .05. A large majority rated the ACASI survey as easier, more enjoyable, more preferable if monthly completion of a survey were required, and more private, and 97% to 99% perfectly answered questions about how to use it. Conclusion: ACASI data collection is reliable among people with bipolar disorder and schizophrenia and could be a valuable tool to improve their care. C1 W Los Angeles VA MIRECC, Los Angeles, CA 90073 USA. RAND Corp, Santa Monica, CA USA. RP Chinman, M (reprint author), W Los Angeles VA MIRECC, 11301 Wilshire Blvd,210A, Los Angeles, CA 90073 USA. EM chinman@rand.org RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [MH 068639] NR 89 TC 51 Z9 52 U1 3 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2004 VL 65 IS 10 BP 1343 EP 1351 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 864SR UT WOS:000224653700007 PM 15491237 ER PT J AU Freudenreich, O Cather, C Evins, AE Henderson, DC Goff, DC AF Freudenreich, O Cather, C Evins, AE Henderson, DC Goff, DC TI Attitudes of schizophrenia outpatients toward psychiatric medications: Relationship to clinical variables and insight SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RATING-SCALE; NONCOMPLIANCE; ADHERENCE; RELAPSE; QUALITY; LIFE AB Background: Attitude toward medications is important for medication adherence. A patient's drug attitude probably reflects a weighing of benefits against experienced or anticipated side effects or risks associated with the medication. We predicted (1) that drug attitudes would be more positive among schizophrenia patients taking second-generation compared to first-generation antipsychotics because of their greater tolerability and efficacy; and (2) that greater insight into illness, fewer extrapyramidal symptoms, and better social functioning would be associated with better attitudes toward psychiatric medication. Method: In a cross-sectional study of 81 DSM-IV-diagnosed schizophrenia outpatients, we used multivariate analysis to determine clinical and demographic predictors of drug attitude. Drug attitude was assessed with the 10-item Drug Attitude Inventory (DAI). The relationship between the DAI and psychopathology, insight, extrapyramidal symptoms, level of functioning, and type of antipsychotic (first-generation versus second-generation versus clozapine) was examined. Results: Less awareness of current symptoms, presence of deficit symptoms, and employment predicted a negative attitude toward psychiatric medications. Extrapyramidal symptoms did not predict drug attitude. Drug attitudes were no different between patients taking first- or second-generation antipsychotics or clozapine. Conclusion: Patients may not favor second-generation over first-generation antipsychotics, and extrapyramidal symptoms may not be a primary factor determining attitudes. While attitudes may be more positive in patients who recognize therapeutic drug effects, patients who work may view medications particularly negatively, possibly due to a sense of stigma. Because drug attitudes may reflect compliance and are difficult to predict, clinicians should inquire directly. C1 Massachusetts Gen Hosp, MGH Shizophrenia Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Schizophrenia Program, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreud@massmed.org NR 29 TC 79 Z9 81 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2004 VL 65 IS 10 BP 1372 EP 1376 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 864SR UT WOS:000224653700011 PM 15491241 ER PT J AU Papakostas, GT Petersen, T Denninger, JW Tossani, E Pava, JA Alpert, JE Nierenberg, AA Fava, M AF Papakostas, GT Petersen, T Denninger, JW Tossani, E Pava, JA Alpert, JE Nierenberg, AA Fava, M TI Psychosocial functioning during the treatment of major depressive disorder with fluoxetine SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SERTRALINE; PLACEBO; IMIPRAMINE; OUTCOMES; ONSET AB Background: Major depressive disorder (MDD) is associated with significant disability, having a profound impact on psychosocial functioning. Therefore, studying the impact of treatment on psychosocial functioning in MDD could help further improve the standard of care. Methods: Two hundred twenty-two MDD outpatients were treated openly with 20 mg fluoxetine for 8 weeks. The self-report version of the Social Adjustment Scale was administered at baseline and during the final visit. We then tested for the relationships between (1) self-report version of the Social Adjustment Scale scores at baseline and clinical response, (2) nonresponse, response and remission status and overall psychosocial adjustment at end point, (3) the number/ severity of residual depressive symptoms and overall psychosocial adjustment at end point in responders, and (4) the time to onset of response and overall psychosocial adjustment at end point. Results: An earlier onset of clinical response predicted better overall psychosocial functioning at end point (P = 0.0440). Responders (n = 128) demonstrated better overall psychosocial adjustment at end point than nonresponders (P = 0.0003), while remitters (n = 64) demonstrated better overall psychosocial adjustment at end point than nonremitted responders (P = 0.0031). In fact, a greater number/ severity of residual symptoms predicted poorer overall psychosocial adjustment at end point in responders (P = 0.0011). Psychosocial functioning at baseline did not predict response. Conclusions: While MDD patients appear equally likely to respond to treatment with fluoxetine, regardless of their level of functioning immediately before treatment, the above results stress the importance of achieving early symptom improvement then followed by full remission of depressive symptoms with respect to restoring psychosocial functioning in MDD. C1 Harvard Univ, Depress Clin & Res Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Papakostas, GT (reprint author), Harvard Univ, Depress Clin & Res Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, 15 Parkman St,WAC 8120, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Tossani, Eliana/0000-0002-6197-4496; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH-48-483-05] NR 14 TC 48 Z9 48 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2004 VL 24 IS 5 BP 507 EP 511 DI 10.1097/01.jcp.0000138761.85363.d5 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 856UD UT WOS:000224069600005 PM 15349006 ER PT J AU Simon, NM Otto, MW Weiss, RD Bauer, MS Miyahara, S Wisniewski, SR Thase, ME Kogan, J Frank, E Nierenberg, AA Calabrese, JR Sachs, GS AF Simon, NM Otto, MW Weiss, RD Bauer, MS Miyahara, S Wisniewski, SR Thase, ME Kogan, J Frank, E Nierenberg, AA Calabrese, JR Sachs, GS CA Pollack, MH STEP-BD Investigators TI Pharmacotherapy for bipolar disorder and comorbid conditions - Baseline data from STEP-BD SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID GENERALIZED ANXIETY DISORDER; I DISORDER; PANIC DISORDER; PRESCRIPTION PATTERNS; PRACTICE GUIDELINES; TREAT ALCOHOLISM; SUBSTANCE-ABUSE; MEDICATIONS; OUTPATIENTS; GABAPENTIN AB Relatively absent from previous studies of the pharmacotherapy for bipolar disorder is examination of the impact of comorbidity on treatment choices. This has occurred despite the presence of high levels of comorbid anxiety and substance use disorders, and the association of these disorders with severity and course markers of bipolar disorder. In this study, we examined comorbid disorders, identified by structured inter-views, and the pharmacotherapy reported at study entry by the first 1000 patients entered into a large, multicenter study of bipolar disorder (Systematic Treatment Enhancement Program for Bipolar Disorder). Our study focused on the degree to which comorbid conditions are linked to the reported use of mood stabilizers deemed "minimally adequate" and the association between specific comorbidities and pharmacotherapy treatment, such as the use of anxiolytics in patients with anxiety disorders. Despite the presence of high levels of comorbidity, the presence of these disorders was only minimally associated with pharmacotherapy. Of the sample of bipolar outpatients, only 59% reported pharmacotherapy use meeting criteria for "minimally adequate" mood stabilizer, regardless of comorbid diagnoses, rapid cycling, or bipolar I or II status. Moreover, the cross-sectional use of "comorbidity-specific" pharmacotherapy for anxiety disorders, substance use disorders, and attention deficit disorder in this outpatient sample of patients with bipolar disorders was limited suggesting that comorbid conditions in patients with bipolar disorder may be undertreated. Our findings highlight the need for greater clinical guidance and treatment options for patients with bipolar disorder and comorbidity. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. Providence Vet Affairs Med Ctr, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIDA NIH HHS [K02 DA00326]; NIMH NIH HHS [MH01381-01, N01MH80001] NR 47 TC 73 Z9 74 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2004 VL 24 IS 5 BP 512 EP 520 DI 10.1097/01.jcp.0000138772.40515.70 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 856UD UT WOS:000224069600006 PM 15349007 ER PT J AU Monnelly, EP Ciraulo, DA Knapp, C LoCastro, J Sepulveda, I AF Monnelly, EP Ciraulo, DA Knapp, C LoCastro, J Sepulveda, I TI Quetiapine for treatment of alcohol dependence SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ADJUNCTIVE THERAPY; SUBSTANCE-ABUSE; SCHIZOPHRENIA; OLANZAPINE; PTSD; RISPERIDONE; CLOZAPINE AB Quetiapine is an atypical antipsychotic that has sedative effects. In this retrospective study, indices of alcohol use were compared for alcohol-dependent subjects who either were (n = 30) or were not (n = 20) treated with quetiapine (25 to 200 mg nightly) for disturbed sleep. Indices examined included total days of abstinence, number of hospitalizations for detoxification, and days to first relapse over I year of clinic treatment. Subjects were male veterans. All subjects had a diagnosis of alcohol dependence, and 90% of subjects in each group were also diagnosed with posttraumatic stress disorder. Both treatment groups contained a large number of subjects treated with psychiatric medications other than quetiapine. Significant differences were not found between the groups with respect to mean age, detoxifications undergone during the previous year, frequency of comorbid posttraumatic stress disorder or depression, or antidepressant use. The mean number of days abstinent was significantly greater, and the number of hospitalizations was significantly lower for the quetiapine than for the control group during the period studied. The mean number of days to relapse approached significance for the quetiapine as compared to the control group. This study has the usual limitations of a retrospective review, including the lack of standardized assessments of alcohol use. The results of this study are consistent with the hypothesis that the use of quetiapine to improve disturbed sleep may help alcohol-dependent patients maintain abstinence, although decreased drinking may also be a result of improving posttraumatic stress disorder symptoms or of a direct action of quetiapine to reduce alcohol use. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. VA Boston Healthcare Syst, Med Dev Res Unit, Boston, MA USA. RP Monnelly, EP (reprint author), VAOPC, 251 Causeway St, Boston, MA 02114 USA. EM edward.monnelly@med.va.gov; dciraulo@bu.edu OI Knapp, Clifford/0000-0003-4482-7678; Ciraulo, Domenic/0000-0001-7706-8765 NR 19 TC 63 Z9 64 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2004 VL 24 IS 5 BP 532 EP 535 DI 10.1097/01.jcp.0000138763.23482.2a PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 856UD UT WOS:000224069600009 PM 15349010 ER PT J AU Cohen, LS Soares, CN Lyster, A Cassano, P Brandes, M Leblanc, GA AF Cohen, LS Soares, CN Lyster, A Cassano, P Brandes, M Leblanc, GA TI Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CLINICAL-TRIAL; SERTRALINE AB The objective of this study was to examine the efficacy and tolerability of intermittent dosing of venlafaxine for the treatment of premenstrual dysphoric disorder. One hundred and twenty-four women aged 18 to 45 years, with regular menstrual cycles and who reported significant premenstrual symptoms, were assessed prospectively to confirm their diagnosis of premenstrual dysphoric disorder. Twenty subjects with confirmed premenstrual dysphoric disorder entered a single-blind, placebo phase (I cycle). Placebo nonresponders (n = 12) received-2 cycles of intermittent (premenstrual) treatment with venlafaxine (75 to 112.5 mg/d). Subjects initiated treatment 14 days before the anticipated onset of menses and discontinued it on the second day of bleeding. Doses could be adjusted after cycle I based on subjects' response and tolerability. Response to treatment was assessed based on changes in the Daily Rating Severity of Problems and Premenstrual Tension Syndrome Questionnaire scores from baseline (before the placebo cycle), as well as Clinical Global Impression-Severity scores. Discontinuation symptoms were assessed between treatment cycles, using the Discontinuation-Emergent Signs and Symptoms questionnaire. Eleven subjects concluded 2 cycles of intermittent dosing with venlafaxine. Nine subjects (81.8%) showed satisfactory response based on Clinical Global Impression of less than or equal to2. Changes in Daily Rating Severity of Problems scores and subscores (depression, physical symptoms, and anger) and in Premenstrual Tension Syndrome Questionnaire scores were significant (P < 0.05 for all comparisons, Wilcoxon tests). Intermittent treatment was well tolerated. This preliminary report suggests that premenstrual use of venlafaxine is an efficacious and well-tolerated treatment for premenstrual dysphoric disorder. C1 Harvard Univ, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cohen, LS (reprint author), Harvard Univ, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Massachusetts Gen Hosp, 15 Parkman St WACC 815, Boston, MA 02114 USA. EM LCOHEN2@PARTNERS.ORG RI Cassano, Paolo/I-6959-2012 NR 12 TC 16 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2004 VL 24 IS 5 BP 540 EP 543 DI 10.1097/01.jcp.0000138767.53976.10 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 856UD UT WOS:000224069600011 PM 15349012 ER PT J AU Biederman, J Monuteaux, MC Doyle, AE Seidman, LJ Wilens, TE Ferrero, F Morgan, CL Faraone, SV AF Biederman, J Monuteaux, MC Doyle, AE Seidman, LJ Wilens, TE Ferrero, F Morgan, CL Faraone, SV TI Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID SOCIAL-ADJUSTMENT INVENTORY; HYPERACTIVITY DISORDER; LEARNING-DISABILITIES; SUSTAINED ATTENTION; RESEARCH CRITERIA; ADOLESCENTS; BOYS; DYSFUNCTION; ADULTS; PERFORMANCE AB The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Warren 705,15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314] NR 61 TC 285 Z9 289 U1 9 U2 61 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2004 VL 72 IS 5 BP 757 EP 766 DI 10.1037/0022-006X.72.5.757 PG 10 WC Psychology, Clinical SC Psychology GA 858TU UT WOS:000224215600002 PM 15482034 ER PT J AU Dayan, S Stashenko, P Niederman, R Kupper, TS AF Dayan, S Stashenko, P Niederman, R Kupper, TS TI Oral epithelial overexpression of IL-1 alpha causes periodontal disease SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE interleukin-1 alpha; periodontitis; inflammation; transgenic; mucosa ID TUMOR-NECROSIS-FACTOR; ANTAGONISTS INHIBIT; INTERLEUKIN-1; BONE; IL-1; RECEPTOR; MICE; KERATINOCYTES; PATHOGENESIS; FIBROBLASTS AB Periodontal disease is a bacterial infection that results in inflammatory destruction of tissues that support the teeth, including connective tissue and bone. In this study, we report that transgenic mice that overexpress the 17-kDa form of IL-1alpha in the basal layer of oral mucosal epithelium develop a syndrome that possesses all of the cardinal features of periodontal disease, including epithelial proliferation and apical migration, loss of attachment, and destruction of cementum and alveolar bone. In this model, bacterial colonization and infection were not required, since levels of periodontal bacteria were equivalent in transgenic and wild-type mice, and continuous treatment with antibiotics from birth did not ameliorate the disease. Our findings therefore indicate that elevated levels of IL-1alpha in the oral microenvironment can mediate all of the clinical features of periodontal disease. C1 Brigham & Womens Hosp, Harvard Inst Med, Dept Dermatol, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Kupper, TS (reprint author), Brigham & Womens Hosp, Harvard Inst Med, Dept Dermatol, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM tskupper@rics.bwh.harvard.edu FU NIAMS NIH HHS [AR-40124, AR-42689]; NIDCR NIH HHS [DE-09018, DE-11664] NR 30 TC 26 Z9 29 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2004 VL 83 IS 10 BP 786 EP 790 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 894MO UT WOS:000226796100009 PM 15381720 ER PT J AU Kamolmatyakul, S Chen, W Yang, S Abe, Y Moroi, R Ashique, AM Li, YP AF Kamolmatyakul, S Chen, W Yang, S Abe, Y Moroi, R Ashique, AM Li, YP TI IL-1 alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappa B pathway SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE interleukin-1alpha; cathepsin K; osteoclast; NF-kappa B; tyrosine kinase ID GENE-EXPRESSION; BONE DESTRUCTION; P65 SUBUNIT; ACTIVATION; LIGAND; CELLS; INTERLEUKIN-1-ALPHA; DIFFERENTIATION; RESORPTION; CYTOKINE AB Interleukin-1alpha (IL-1alpha) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1alpha up-regulates the expression of cathepsin K protein, a key protease in bone resorption, by five-fold. Northern blot analysis and promoter analysis show that this induction occurs at the transcriptional level, in a dose-responsive and time-dependent manner. No increase in expression occurs in the presence of either pyrrolidine dithiocarbamate ( PDTC), a selective inhibitor of NF-kappaB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1alpha up-regulation may be via the tyrosine kinase-NF-kappaB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-kappaB, suppress the IL-1alpha-induced expression of cathepsin K. We therefore conclude that IL-1alpha up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-kappaB pathway. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Harvard Sch Dent Med, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIAMS NIH HHS [R01 AR044741, R01 AR048133, AR48133-01, AR44741] NR 24 TC 20 Z9 21 U1 0 U2 3 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2004 VL 83 IS 10 BP 791 EP 796 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 894MO UT WOS:000226796100010 PM 15381721 ER PT J AU Kysia, RF Brown, DFM Nadel, ES AF Kysia, RF Brown, DFM Nadel, ES TI Case presentations of the Harvard Emergency Medicine Residency SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID CLINICAL MANIFESTATIONS; TUBERCULOSIS; INFECTION; AIDS; AFRICA C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2004 VL 27 IS 3 BP 285 EP 289 DI 10.1016/j.jemermed.2004.06.005 PG 5 WC Emergency Medicine SC Emergency Medicine GA 856VL UT WOS:000224073300015 PM 15388218 ER PT J AU Waldrop, AE Resick, PA AF Waldrop, AE Resick, PA TI Coping among adult female victims of domestic violence SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE battered women; coping; environmental factors; psychological difficulties ID POSTTRAUMATIC-STRESS-DISORDER; BATTERED WOMEN; ABUSIVE RELATIONSHIP; SELF-BLAME; STRATEGIES; VICTIMIZATION; DETERMINANTS; RESPONSES; SYMPTOMS; TIME AB This paper examines the current literature regarding coping among battered women. It considers a number of contextual factors that are related to women's choices in coping with partner abuse, including factors related to the relationship (e.g., frequency and severity of abuse, length of relationship) and women's resources (e.g., social support, financial resources). Relationships between different forms of coping and psychological outcomes are also examined. As the research in domestic violence coping is somewhat lacking in coherence, theories, and models from the broader coping literature are used to organize the findings from the domestic violence field. Methodological concerns, such as research methods, measurement issues, and sampling, are raised throughout the paper. Suggestions for future research are made. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. RP Waldrop, AE (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA. EM waldrop@musc.edu NR 48 TC 68 Z9 69 U1 2 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD OCT PY 2004 VL 19 IS 5 BP 291 EP 302 DI 10.1023/B:JOFV.0000042079.91846.68 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 855NE UT WOS:000223979500004 ER PT J AU Dresselhaus, TR Peabody, JW Luck, J Bertenthal, D AF Dresselhaus, TR Peabody, JW Luck, J Bertenthal, D TI An evaluation of vignettes for predicting variation in the quality of preventive care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE compliance; preventive care guidelines; physician practice; clinical vignettes; quality of care ID STANDARDIZED PATIENTS; INFLUENZA VACCINATION; CLINICAL-PERFORMANCE; SIMULATED PATIENTS; CONTROLLED-TRIAL; HEALTH-CARE; PHYSICIANS; GUIDELINES; REMINDERS; MORTALITY AB OBJECTIVE: Clinical vignettes offer an inexpensive and convenient alternative to the benchmark method of chart audits for assessing quality of care. We examined whether vignettes accurately measure and predict variation in the quality of preventive care. DESIGN: We developed scoring criteria based on national guidelines for 11 prevention items, categorized as vaccine, vascular-related, cancer screening, and personal behaviors. Three measurement methods were used to ascertain the quality of care provided by clinicians seeing trained actors (standardized patients; SPs) presenting with common outpatient conditions: 1) the abstracted medical record from an SP visit; 2) SP reports of physician practice during those visits; and 3) physician responses to matching computerized case scenarios (clinical vignettes). SETTING: Three university-affiliated (including 2 VA) and one community general internal medicine clinics. PATIENTS/PARTICIPANTS: Seventy-one randomly selected physicians from among eligible general internal medicine residents and attending physicians. MEASUREMENTS AND MAIN RESULTS: Physicians saw 480 SPs (120 at each site) and completed 480 vignettes. We calculated the proportion of prevention items for each visit reported or recorded by the 3 measurement methods. We developed a multiple regression model to determine whether site, training level, or clinical condition predicted prevention performance for each measurement method. We found that overall prevention scores ranged from 57% (SP) to 54% (vignettes) to 46% (chart abstraction). Vignettes matched or exceeded SP scores for 3 prevention categories (vaccine, vascular-related, and personal behavior). Prevention quality varied by site (from 40% to 67%) and was predicted similarly by vignettes and SPs. CONCLUSIONS: Vignettes can measure and predict prevention performance. Vignettes may be a less costly way to assess prevention performance that also controls for patient case-mix. C1 Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA 94105 USA. Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA USA. Calif State Univ Los Angeles, RAND, Sch Publ Hlth, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Ctr Study Hlth Care Provider Behav, Los Angeles, CA USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, Inst Global Hlth, 74 New Montgomery St,Suite 508, San Francisco, CA 94105 USA. EM peabody@psg.ucsf.edu NR 28 TC 61 Z9 61 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2004 VL 19 IS 10 BP 1013 EP 1018 DI 10.1007/s11606-004-0003-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 860MG UT WOS:000224347100004 PM 15482553 ER PT J AU de la Rosa, DA Paunescu, TG Els, WJ Helman, SI Canessa, CM AF de la Rosa, DA Paunescu, TG Els, WJ Helman, SI Canessa, CM TI Mechanisms of regulation of epithelial sodium channel by SGK1 in A6 cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE ENaC; serum- and glucocorticoid-induced kinase; sodium reabsorption; open probability; channel density ID BLOCKER-SENSITIVE ENACS; NA+ TRANSPORT; APICAL MEMBRANE; FROG-SKIN; DEPENDENT EXPRESSION; SGK1-KNOCKOUT MOUSE; SURFACE EXPRESSION; XENOPUS-OOCYTES; INDUCED KINASE; ALDOSTERONE AB The serum and glucocorticoid induced kinase 1 (SGK1) participates in the regulation of sodium reabsorption in the distal segment of the renal tubule, where it may modify the function of the epithelial sodium channel (ENaC). The molecular mechanism underlying SGK1 regulation of ENaC in renal epithelia] cells remains controversial. We have addressed this issue in an A6 renal epithelial cell line that expresses SGK1 under the control of a tetracycline-inducible system. Expression of a constitutively active mutant of SGK1 (SGK1(S425D)(T)) induced a sixfold increase in amiloride-sensitive short-circuit current (I-sc). Using noise analysis we demonstrate that SGK1 effect on I-sc is due to a fourfold increase in the number of functional ENaCs in the membrane and a 43% increase in channel open probability. Impedance analysis indicated that SGK1(S425D)(T) increased the absolute value of cell equivalent capacitance by an average of 13.7%. SGK1(S425D)(T) also produced a 1.6-1.9-fold increase in total and plasma membrane subunit abundance, without changing the half-life of channels in the membrane. We conclude that in contrast to aldosterone, where stimulation of transport can be explained simply by an increase in channel synthesis, SGK1 effects are more complex and involve at least three actions: (1) increase of ENaC open probability; (2) increase of subunit abundance within apical membranes and intracellular compartments; and (3) activation of one or more pools of preexistent channels within the apical membranes and/or intracellular compartments. C1 Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. RP Canessa, CM (reprint author), Yale Univ, Sch Med, Dept Cellular & Mol Physiol, Sterling Hall Med,B-121,333 Cedar St, New Haven, CT 06510 USA. EM cecilia.canessa@yale.edu RI Alvarez de la Rosa, Diego/H-8500-2015 OI Alvarez de la Rosa, Diego/0000-0002-4324-2793 NR 41 TC 36 Z9 36 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD OCT PY 2004 VL 124 IS 4 BP 395 EP 407 DI 10.1085/jgp.200409120 PG 13 WC Physiology SC Physiology GA 860YL UT WOS:000224380500009 ER PT J AU Huq, S Liu, Y Benichou, G Dana, MR AF Huq, S Liu, Y Benichou, G Dana, MR TI Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; ALLOGRAFT-REJECTION; DENDRITIC CELLS; LYMPH-NODES; MICE; HISTOCOMPATIBILITY; SURVIVAL; TISSUE; SKIN; ALLORECOGNITION AB Corneal grafts were until recently considered entirely devoid of resident APCs, giving rise to the tenet that alloantigen recognition is mediated exclusively by the indirect (host APC-dependent) pathway. The recent discovery of a resident myeloid corneal dendritic cell population that is normally MHC class II- but can readily up-regulate class II expression during inflammation led us to hypothesize that under certain conditions the direct pathway of allosensitization becomes operative. To test this, corneal allotransplants were performed in either inflamed (high-risk (HR)) or uninflamed (low-risk (LR)) host beds in mice, and the frequencies of host T cells activated via the direct pathway were determined. We found that directly primed CD4(+) T cells were detected in the HR but not LR setting, and these cells displayed a clear Th1 phenotype by 2 wk after grafting. Moreover, the use of MHC class II knockout donor tissue led to significantly enhanced survival of HR but not LR allografts. Finally, we show that donor corneal APC demonstrate high expression of CD40, CD80, and CD86 costimulatory molecules when derived from HR but not LR grafts. These data are the first to report that a functional donor APC-dependent direct response is elicited in corneal transplant hosts when the graft bed is inflamed and underscore the relevance of the graft microenvironment in dictating the pathway of allosensitization. C1 Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Schepens Eye Res Inst, Dept Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Inst Transplantat, Boston, MA 02113 USA. Harvard Univ, Sch Med, Boston, MA 02113 USA. RP Dana, MR (reprint author), Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu FU PHS HHS [13310, R01-12963] NR 31 TC 51 Z9 55 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2004 VL 173 IS 7 BP 4464 EP 4469 PG 6 WC Immunology SC Immunology GA 856VF UT WOS:000224072600026 PM 15383577 ER PT J AU Moll, T Nitschke, L Carroll, M Ravetch, JV Izui, S AF Moll, T Nitschke, L Carroll, M Ravetch, JV Izui, S TI A critical role for Fc gamma RIIB in the induction of rheumatoid factors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AUTOIMMUNE-DISEASE; DEFICIENT MICE; COMPLEMENT C4; MURINE LUPUS; LPR/LPR MICE; B-CELLS; CD22; GENE; RECEPTOR; PATHOGENICITY AB Rheumatoid factors (RF) are autoantibodies with specificity for the Fc portion of IgG, and IgG-containing immune complexes are likely to be the major source of RF autoantigens. Therefore, the activation of RF-producing B cells could be controlled specifically through recognition of IgG immune complexes by the low-affinity IgG FcR, FcgammaRIIB, a potent negative regulator of the BCR. To test this possibility, we determined the development of RF in C57BL/6 (1 6) mice lacking FcgammaRIIB, in relation to the H2 haplotype, complement C3, and the Y-linked autoimmune acceleration (Yaa) mutation. FcgammaRIIB-null B6 mice displayed substantial anti-IgG2a RF activities in their sera, in addition to anti-DNA autoantibodies. Their, RF and anti-DNA responses were linked to the H2(b) haplotype, but were suppressed almost completely by the H2(d) haplotype. Strikingly, the absence of C3 failed to modulate RF production, but strongly inhibited anti-DNA production. Furthermore, we observed that partial FcgammaRIIB deficiency (i.e., heterozygous level of FcgammaRIIB expression) was sufficient to induce the production of RF and anti-DNA autoantibodies in the presence of the Yaa mutation. In contrast to FcgammaRIIB, the deficiency in another BCR negative regulator, CD22, was unable to promote RF and anti-DNA autoimmune responses in B6 mice. Our results indicate that RF autoimmune responses are critically controlled by FcgammaRIIB, together with the H2(b) and Yaa gene, while C3 regulates positively and specifically, anti-DNA, but not RF autoimmune responses. C1 Univ Geneva, Med Ctr, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland. Univ Wurzburg, Inst Virol & Immunbiol, D-8700 Wurzburg, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA. RP Izui, S (reprint author), Univ Geneva, Med Ctr, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland. EM Shozo.Izui@medecine.unige.ch NR 35 TC 19 Z9 20 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2004 VL 173 IS 7 BP 4724 EP 4728 PG 5 WC Immunology SC Immunology GA 856VF UT WOS:000224072600058 PM 15383609 ER PT J AU Li, W Henry, G Fan, JH Bandyopadhyay, B Pang, K Garner, W Chen, M Woodley, DT AF Li, W Henry, G Fan, JH Bandyopadhyay, B Pang, K Garner, W Chen, M Woodley, DT TI Signals that initiate, augment, and provide directionality for human keratinocyte motility SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ECM; growth factor; human keratinocyte; motility; signal transduction; wound healing ID EPIDERMAL-GROWTH-FACTOR; FIBROBLAST MIGRATION; CELL-MIGRATION; ALPHA(V)BETA(3) INTEGRIN; EXTRACELLULAR-MATRIX; PHAGOKINETIC TRACKS; EPITHELIAL-CELLS; DERMAL COLLAGEN; EGF RECEPTOR; FACTOR-BB AB Human keratinocytes (HK) migration plays a critical role in the re-epithelialization of acute skin wounds. Although extracellular matrices (ECM) and growth factors (GF) are the two major pro-motility signals, their functional relationship remains unclear. We investigated how ECM and GF regulate HK motility under defined conditions: (1) in the absence of GF and ECM and (2) with or without GF with cells apposed to a known pro-motility ECM. Our results show that HK migrate on selected ECM even in the total absence of GF. This suggests that certain ECM alone are able to "initiate" HK migration. Unlike ECM, however, GF alone cannot initiate HK migration. HK cannot properly migrate when plated in the presence of GF, regardless of the concentration, without an ECM substratum. The role of GF, instead, is to augment ECM-initiated motility and provide directionality. To gain insights into the mechanism of action by ECM and GF, we compared, side-by-side, the roles of three major mitogen-activated protein kinase cascades, extracellular-signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK). Our data show that ERK1/2 is involved in mediating collagen's initiation signal and GF's augmentation signal. p38 is specific for GF's augmentation signal. JNK is uninvolved in HK motility. Constitutively activated p38 and ERK1/2 alone could not initiate HK migration. Co-expression of both constitutively activated p38 and ERK1/2, however, could partially mimic the pro-motility effects of collagen and GF. This study reveals for the first time the specific functions of ECM and GF in cell motility. C1 Univ So Calif, Dept Med, Div Dermatol, Keck Sch Med, Los Angeles, CA 90033 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ So Calif, Dept Surg, Div Plast Surg, Keck Sch Med, Los Angeles, CA USA. RP Li, W (reprint author), Univ So Calif, Dept Med, Div Dermatol, Keck Sch Med, 1303 N Mission Rd, Los Angeles, CA 90033 USA. EM wli@usc.edu NR 58 TC 49 Z9 50 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2004 VL 123 IS 4 BP 622 EP 633 DI 10.1111/j.0022-202X.2004.23416.x PG 12 WC Dermatology SC Dermatology GA 855OF UT WOS:000223982900010 PM 15373765 ER PT J AU Virella, G Thorpe, SR Alderson, NL Derrick, MB Chassereau, C Rhett, JM Lopes-Virella, ME AF Virella, G Thorpe, SR Alderson, NL Derrick, MB Chassereau, C Rhett, JM Lopes-Virella, ME TI Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies SO JOURNAL OF LIPID RESEARCH LA English DT Article DE low density lipoprotein modifications; low density lipoprotein autoantibodies; modified low density lipoprotein antibodies; immunology of atherosclerosis; autoimmunity; atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; ADVANCED GLYCATION ENDPRODUCTS; ATHEROSCLEROTIC LESIONS; OXIDIZED LDL; OXIDATIVE MODIFICATION; DIABETES-MELLITUS; IMMUNE-COMPLEXES; LYSINE RESIDUES; END-PRODUCT; EPITOPES AB Humans and laboratory animals recognize human modified LDL as immunogenic. Immune complexes (ICs) isolated from human sera contain malondialdehyde-modified LDL (MDA-LDL) and N-epsilon(carboxymethyl)lysine-modified LDL (CML-LDL) as well as antibodies reacting with MDA-LDL, copper-oxidized LDL (OxLDL), CML-LDL, and advanced glycosylation end product (AGE)-modified LDL. OxLDL and AGE-LDL antibodies isolated from human sera recognize the same LDL modifications and do not react with modified non-LDL proteins. Rabbit antibodies have different reactivity patterns: MDA-LDL antibodies react strongly with MDA-LDL and MDA-BSA but weakly with OxLDL; OxLDL antibodies react strongly with OxLDL and weakly with MDA-LDL; CML-LDL antibodies react with CML-LDL > CML-BSA > AGE-LDL > OxLDL; AGE-LDL antibodies react strongly with AGE-LDL, react weakly with OxLDL, and do not react with CML-LDL. Thus, human and rabbit antibodies seem to recognize different epitopes. Capture assays carried out with all rabbit antibodies showed binding of apolipoprotein B-rich lipoproteins isolated from ICs, suggesting that laboratory-generated epitopes are expressed by in vivo-modified LDL, although they are not necessarily recognized by the human immune system. jlr Thus, the definition of immunogenic forms of modified LDL eliciting human autoimmune responses requires the isolation and characterization of autoantibodies and modified LDL from human samples, whereas rabbit antibodies can be used to detect in vivo-modified human LDL. -Virella, G., S. R. Thorpe, N. L. Alderson, M. B. Derrick, C. Chassereau, J. M. Rhett, and M. E Lopes-Virella. Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Nutr, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Virella, G (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM virellag@musc.edu FU NHLBI NIH HHS [P01 HL 55782]; NIDDK NIH HHS [DK 19971] NR 28 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2004 VL 45 IS 10 BP 1859 EP 1867 DI 10.1194/jlr.M400095-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 859ZR UT WOS:000224307400008 PM 15258197 ER PT J AU Elosua, R Ordovas, JM Cupples, LA Fox, CS Polak, JF Wolf, PA D'Agostino, RA O'Donnell, CJ AF Elosua, R Ordovas, JM Cupples, LA Fox, CS Polak, JF Wolf, PA D'Agostino, RA O'Donnell, CJ TI Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE genetics; atherosclerosis; carotid artery; lipoprotein; apolipoprotein E genotype ID APOLIPOPROTEIN-E POLYMORPHISM; INTIMA-MEDIA THICKNESS; ARTERIAL-WALL THICKNESS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ASYMPTOMATIC ADULTS; TRIGLYCERIDE LEVELS; RISK-FACTORS; E ALLELES; E GENE AB The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (010), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). jlr The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men. -Elosua, R., J. M. Ordovas, L. A. Cupples, C. S. Fox, J. F. Polak, P. A. Wolf, R. A. D'Agostino, Sr., and C. J. O'Donnell. Association of APOE genotype with carotid atherosclerosis in men and women. The Framingham Heart Study. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Boston Univ, Dept Neurol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM codonnell@partners.org OI ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL 54776, N01 HC 25195]; NINDS NIH HHS [5R01 NS 17950-22] NR 46 TC 51 Z9 52 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2004 VL 45 IS 10 BP 1868 EP 1875 DI 10.1194/jlr.M4000114-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 859ZR UT WOS:000224307400009 PM 15258198 ER PT J AU [Anonymous] AF [Anonymous] TI Broad activity of human anti-HIV monoclonal antibodies in vitro and in vivo SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract RP Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2004 VL 33 IS 5-6 BP 285 EP 285 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 858GC UT WOS:000224179300019 ER PT J AU Wilson, EM Diwan, A Spinale, FG Mann, DL AF Wilson, EM Diwan, A Spinale, FG Mann, DL TI Duality of innate stress responses in cardiac injury, repair, and remodeling SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE myocardium; cardiac injury; innate stress response ID TUMOR-NECROSIS-FACTOR; ISCHEMIA-REPERFUSION INJURY; LEUKEMIA-INHIBITORY FACTOR; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; ADULT FELINE MYOCARDIUM; FACTOR-ALPHA GENE; TRANSGENIC MICE; ANGIOTENSIN-II; INDUCED EXPRESSION AB The ability of the myocardium to successfully adapt to cardiac injury ultimately determines whether the heart will decompensate and fail, or whether instead it will maintain preserved function. Despite the importance of the myocardial response to cardiac injury, very little is known with respect to the biochemical mechanisms that are responsible for mediating and integrating the stress response in the heart. In the present review we will summarize recent experimental material which suggests that the heart possess a germ-line encoded "innate" stress response that is activated in response to diverse forms of tissue injury. The extant literature suggests that this innate stress response plays an important role in initiating and integrating homeostatic responses within the heart. Nonetheless, as will be discussed further herein, these inflammatory mediators all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. (C) 2004 Elsevier Ltd. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Vet Adm Med Ctr, Winters Ctr Heart fAILURE rES, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Med Univ S Carolina, Dept Surg Cardiothorac Res, Charleston, SC 29425 USA. RP Mann, DL (reprint author), Baylor Coll Med, Michael E DeBakey Vet Adm Med Ctr, Winters Ctr Heart fAILURE rES, Dept Med, 6565 Fannin,MS 524, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL 58081-01, HL 42250-10/10, R01 HL 61543-01] NR 74 TC 31 Z9 35 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD OCT PY 2004 VL 37 IS 4 BP 801 EP 811 DI 10.1016/j.yjmcc.2004.05.028 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 859TR UT WOS:000224291300001 PM 15380670 ER PT J AU Li, HM Rao, AJ Hogan, PG AF Li, HM Rao, AJ Hogan, PG TI Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE calcineurin; NFAT; phosphatase; protein-protein interaction; T cell activation ID PROTEIN PHOSPHATASE-1 REGULATION; CYCLOSPORINE-A; TRANSCRIPTION FACTORS; SELECTIVE-INHIBITION; SKELETAL-MUSCLE; KINASE-A; BINDING; COMPLEX; FAMILY; SITE AB Calcineurin is a phosphoprotein phosphatase that channels intracellular Ca signals into multiple biological pathways. Calcineurin is known to interact directly with its substrate nuclear factor of activated T cells (NEAT or NFATc), with other substrates, and with several targeting and scaffold proteins including AKAP79 and Cabin1/cain. The calcineurin-NFAT interaction depends on recognition of a PxIxIT sequence motif present in NFAT-family proteins and in certain other calcineurin-interacting proteins. Here, we define the structural basis for the interaction of calcineurin with NFAT and with other proteins possessing the PxIxIT motif. The calcineurin-PxIxIT contact has a direct parallel in the contact of protein phosphatase 1 with its regulatory proteins, suggesting that the evolution of these related phosphatases involved local remodelling of an ancestral docking site. (C) 2004 Elsevier Ltd. All rights reserved. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hogan, PG (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM hogan@cbr.med.harvard.edu FU NIAID NIH HHS [AI 40127, AI43726] NR 58 TC 46 Z9 47 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 1 PY 2004 VL 342 IS 5 BP 1659 EP 1674 DI 10.1016/j.jmb.2004.07.068 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 857RH UT WOS:000224135500026 PM 15364589 ER PT J AU Marci, CD Moran, EK Orr, SP AF Marci, CD Moran, EK Orr, SP TI Physiologic evidence for the interpersonal role of laughter during psychotherapy SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE psychophysiology; laughter; psychotherapy; skin conductance ID MIRTHFUL LAUGHTER; HUMOR; EMPATHY; HUMANS AB The role of laughter during psychotherapy is poorly understood. This study examined 10 unique sessions of psychodynamic psychotherapy with digital videotape and simultaneous measures of skin conductivity (SC) from patients and therapists. Independent observers coded laugh episodes using published criteria. Observers identified 167 laugh responses. Of the 119 patient laughs, 91 (76.5%) were patient as speaker, compared with 28 (23.4%) as nonspeaker audience. In contrast, of the 48 therapist laughs, only five (10.4%) were therapist as speaker, whereas 43 (90.3%) were as nonspeaker audience. The difference was highly significant (p < .001). Physiologic data showed that mean SC level increased regardless of role as patient, therapist, speaker, or audience (p < .001). Two-factor analysis of-variance indicated that SC change scores were significantly larger when patients and therapists laughed together compared with laughing alone (p < .05). The results support an empirically based approach to the study of laughter and the use of psychophysiology as a measure of process during psychotherapy. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Vet Affairs, Med Ctr, Manchester, NH USA. RP Marci, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. FU NIMH NIH HHS [T32MH16259-23] NR 39 TC 11 Z9 11 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2004 VL 192 IS 10 BP 689 EP 695 DI 10.1097/01.nmd.0000142032.04196.63 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 862RL UT WOS:000224508500007 PM 15457112 ER PT J AU Fox, JH Barber, DS Singh, B Zucker, B Swindell, MK Norflus, F Buzescu, R Chopra, R Ferrante, RJ Kazantsev, A Hersch, SM AF Fox, JH Barber, DS Singh, B Zucker, B Swindell, MK Norflus, F Buzescu, R Chopra, R Ferrante, RJ Kazantsev, A Hersch, SM TI Cystamine increases L-cysteine levels in Huntington's disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cystamine; glutathione; Huntington's disease; L-cysteine; neuroprotection; oxidative stress ID 3-NITROPROPIONIC ACID NEUROTOXICITY; OXIDATIVE DAMAGE; NEURODEGENERATIVE DISEASES; CEREBROSPINAL-FLUID; IN-SITU; TRANSGLUTAMINASE; MICE; MUTATION; EXPRESSION; TOXICITY AB Cystamine, a small disulfide-containing chemical, is neuroprotective in a transgenic mouse and a Drosophila model of Huntington's disease (HD) and decreases huntingtin aggregates in an in vitro model of HD. The mechanism of action of cystamine in these models is widely thought to involve inhibition of transglutaminase mediated cross-linking of mutant huntingtin in the process of aggregate formation/stabilization. In this study we show that cystamine, both in vitro and in a transgenic mouse model of HD (R6/2), increases levels of the cellular antioxidant L-cysteine. Several oxidative stress markers increase in HD brain. We provide further evidence of oxidative stress in mouse HD by demonstrating compensatory responses in R6/2 HD brains. We found age-dependent increases in forebrain glutathione (GSH), and increased levels of transcripts coding for proteins involved in GSH synthesis and detoxification pathways, as revealed by quantitative PCR analysis. Given the general importance of oxidative stress as a mediator of neurodegeneration we propose that an increase in brain L-cysteine levels could be protective in HD. Furthermore, cystamine was dramatically protective against 3-nitropropionic acid-induced striatal injury in mice. We suggest that cystamine's neuroprotective effect in HD transgenic mice results from pleiotropic effects that include transglutaminase inhibition and antioxidant activity. C1 Massachusetts Gen Hosp, Dept Neurol, Massgen Inst Neurodegenerat Dis, Charlestown, MA USA. Univ Florida, Ctr Environm Hlth & Toxicol, Gainesville, FL USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. RP Hersch, SM (reprint author), Massgen Inst Neurodegenerat Dis, MGH E Bldg 114-2001,114 16th St, Charlestown, MA 02129 USA. EM Hersch@helix.mgh.harvard.edu FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS045806, NS045242, NS35255] NR 49 TC 81 Z9 81 U1 1 U2 9 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2004 VL 91 IS 2 BP 413 EP 422 DI 10.1111/j.1471-4159.2004.02726.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 856UH UT WOS:000224070100016 PM 15447674 ER PT J AU Smith, EE Fitzsimmons, AL Nogueira, RG Singhal, AB AF Smith, EE Fitzsimmons, AL Nogueira, RG Singhal, AB TI Spontaneous hyperacute postischemic hemorrhage leading to death SO JOURNAL OF NEUROIMAGING LA English DT Article DE brain MRI; stroke; hemorrhagic conversion ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; INTRACEREBRAL HEMORRHAGE; COMPUTED TOMOGRAPHY; TRANSFORMATION; MRI; MICROBLEEDS; DIAGNOSIS; CT AB Hyperacute, spontaneous, and severe parenchymal postischemic hemorrhage is considered rare but might be frequently misdiagnosed as primary intracerebral hemorrhage. The authors report 2 patients with catastrophic postischemic hemorrhage unrelated to anticoagulation, thrombolytics, or coagulopathy. Patient 1 was a 73-year-old woman with left posterior frontal lobe infarction, followed at 5.5 hours by massive postischemic hemorrhage leading to death. Patient 2 was a 52year-old man with recent brain irradiation who developed left middle cerebral artery occlusion and basal ganglia infarction. Initial gradientecho magnetic resonance imaging (MRI) showed petechial hemorrhage within areas of infarction and widespread old microbleeds. He developed massive postischemic hemorrhage at 12 hours, leading to death. The authors conclude that early brain imaging is essential to distinguish postischemic from primary brain hemorrhage. In patients with ischemic stroke, MRI findings such as hyperacute petechial hemorrhage or chronic cerebral microbleeds might predict subsequent parenchymal hemorrhage and thus have implications for tissue plasminogen activator use. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK 725, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [1K23 NS046327-01] NR 20 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2004 VL 14 IS 4 BP 361 EP 364 DI 10.1177/1051228404264937 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 876DE UT WOS:000225475300010 PM 15358958 ER PT J AU El-Shabrawi, Y Walch, A Hermann, J Egger, G Foster, CS AF El-Shabrawi, Y Walch, A Hermann, J Egger, G Foster, CS TI Inhibition of MMP-dependent chemotaxis and amelioration of experimental autoimmune uveitis with a selective metalloproteinase-2 and-9 inhibitor SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE rodent; T-lymphocytes; autoimmunity; cell trafficking; EAU; MMP; uveitis ID MATRIX METALLOPROTEINASES; BASEMENT-MEMBRANE; LYMPHOCYTES; CELLS; UVEORETINITIS; MIGRATION; ENCEPHALOMYELITIS; INTERLEUKIN-1; DEXAMETHASONE; GELATINASES AB The chemotaxis of inflammatory cells depends on proteolytic disruption of extracellular matrix components. The metalloproteinases (MMP)-2 and -9 enable T -lymphocytes to pass through basement membranes. Selective inhibition of only MMP-2 and -9 almost completely abolished the ability of lymphocytes to digest collagen. The chemotaxis of lymphocytes was reduced 40%. In our in-vivo model of experimental autoimmune uveitis (EAU), 46% of the animals in the treated group remained disease-free, whereas all animals in the control group developed EAU. The mean activity of the disease was also statistically significantly reduced. The data suggest that selective MMP-2 and -9 inhibition might be a treatment option. (C) 2004 Elsevier B.V. All rights reserved. C1 Med Univ Graz, Dept Ophthalmol, A-8036 Graz, Austria. Med Univ Graz, Dept Internal Med, A-8036 Graz, Austria. Med Univ Graz, Dept Expt Pathol, A-8036 Graz, Austria. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02115 USA. RP El-Shabrawi, Y (reprint author), Med Univ Graz, Dept Ophthalmol, Auenbruggerpl 4, A-8036 Graz, Austria. EM yosuf.elshabrawi@meduni-graz.at RI Walch, Axel/B-4554-2012 OI Walch, Axel/0000-0001-5578-4023 NR 33 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 2004 VL 155 IS 1-2 BP 13 EP 20 DI 10.1016/j.jneuroim.2004.05.010 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VV UT WOS:000224003900002 PM 15342192 ER PT J AU Peterka, RJ Gianna-Poulin, CC Zupan, LH Merfeld, DM AF Peterka, RJ Gianna-Poulin, CC Zupan, LH Merfeld, DM TI Origin of orientation-dependent asymmetries in vestibulo-ocular reflexes evoked by caloric stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENT RESPONSES; GRAVITO-INERTIAL CUES; VISUAL-VESTIBULAR INTERACTIONS; LINEAR HEAD MOTION; SEMICIRCULAR CANALS; SQUIRREL-MONKEY; SPATIAL ORIENTATION; ECCENTRIC ROTATION; VELOCITY STORAGE; NYSTAGMUS AB A caloric stimulus evokes primarily a horizontal vestibulo-ocular reflex (VOR) when subjects are in a supine or prone orientation with the horizontal semicircular canal plane oriented vertically. In both monkeys and humans, the magnitude of VOR eye movements is greater in the supine than in the prone orientation, indicating that some factor or factors, other than the conventionally accepted convective stimulation of the horizontal canals, contributes to the generation of the VOR. We used long-duration caloric irrigations and mathematical models of canal-otolith interactions to investigate factors contributing to the prone/supine asymmetry. Binaural caloric irrigations were applied for 7.5 or 9.5 min with subjects in a null orientation with horizontal canals in the earth-horizontal plane (control trial), or with the subject's pitch orientation periodically changing between null, supine, and prone positions with each orientation held for 30 s (caloric step trial). The control trial responses identified a small response attributable to a direct thermal effect on vestibular afferent activity that accounted for only 15% of the observed prone/supine asymmetry. We show that the gravito-inertial force resolution hypothesis for sensory integration of canal and otolith information predicts that the central processing of canal and otolith information produces an internal estimate of motion that includes both a rotational motion component and a linear acceleration component. These components evoke a horizontal angular VOR and linear VOR, which combine additively in the supine orientation, but subtract in the prone orientation, thus accounting for the majority of the observed prone/supine asymmetry. C1 Oregon Hlth & Sci Univ, Inst Neurol Sci, Beaverton, OR 97006 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vetibular Physiol Lab, Boston, MA 02114 USA. RP Peterka, RJ (reprint author), Oregon Hlth & Sci Univ, Inst Neurol Sci, OHSU W Campus,Bldg 1,505 NW 185th Ave, Beaverton, OR 97006 USA. EM peterkar@ohsu.edu FU NIDCD NIH HHS [R01 DC-04158] NR 44 TC 17 Z9 18 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2004 VL 92 IS 4 BP 2333 EP 2345 DI 10.1152/jn.00174.2004 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 855DY UT WOS:000223954500036 PM 15175373 ER PT J AU Kondziolka, D Lunsford, LD Loeffler, JS Friedman, WA AF Kondziolka, D Lunsford, LD Loeffler, JS Friedman, WA TI Radiosurgery and radiotherapy: observations and clarifications SO JOURNAL OF NEUROSURGERY LA English DT Article DE radiosurgery; radiotherapy; fractionation; neurosurgery ID STEREOTACTIC RADIOSURGERY; RADIOBIOLOGY AB Object. Radiosurgery and radiation therapy represent important but unique treatment paradigms for patients with certain neoplasms, vascular lesions, or functional disorders. The authors discuss their differences. Methods. Reviewing the authors' experiences shows how the roles of these approaches vary just as their techniques differ. The distinct differences include the method of target localization (intraoperative compared with pretreatment) and irradiation (focused compared with wide-field), their radiobiology (effects of a single high-dose compared with multiple fractions), the physicians and other health personnel involved in the conduct of these procedures (surgical team compared with radiation team), and the expectations that follow treatment. During the last decade, considerable confusion has grown regarding nomenclature, requisite physician training, and the roles of the physician and surgeon. Ten years ago, two task forces on radiosurgery were created by national organizations in neurosurgery and radiation oncology to address these issues of procedural conduct and quality-assurance requirements. At the present time these guidelines are widely ignored. Currently, many patients, payers, and regulatory agencies are bewildered. What are the differences among stereotactic radiosurgery, fractionated radiation therapy, and stereotactic radiation therapy? Radiosurgery is to radiation therapy as microsurgery is to "microtherapy." Conclusions. In this report the authors discuss terminology, training, and physician roles in this expanding field. C1 UPMC, Dept Neurol Surg, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA 15260 USA. Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kondziolka, D (reprint author), UPMC, Dept Neurol Surg, Suite B-400,200 Lothrop St, Pittsburgh, PA 15213 USA. EM koiidziolkads@upmc.edu NR 15 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2004 VL 101 IS 4 BP 585 EP 589 DI 10.3171/jns.2004.101.4.0585 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 865MP UT WOS:000224707500007 PM 15481710 ER PT J AU Ghogawala, Z Benzel, EC Amin-Hanjani, S Barker, FG Harrington, JF Magge, SN Strugar, J Couman, JVCE Borges, LF AF Ghogawala, Z Benzel, EC Amin-Hanjani, S Barker, FG Harrington, JF Magge, SN Strugar, J Couman, JVCE Borges, LF TI Prospective outcomes evaluation after decompression with or without instrumented fusion for lumbar stenosis and degenerative Grade I spondylolisthesis SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE lumbar spine; decompression; fusion; spondylolisthesis; stenosis; prospective clinical trial ID LOW-BACK-PAIN; SPINAL STENOSIS; SHORT FORM-36; LAMINECTOMY; ARTHRODESIS; SURGERY AB Object. There is considerable debate among spine surgeons regarding whether fusion Should be used to augment decompressive surgery in patients with symptomatic lumbar spinal stenosis involving Grade I degenerative spondylolisthesis. The authors prospectively evaluated the outcomes of patients treated between 2000 and 2002 at two institutions to determine whether fusion improves functional outcome I year after surgery. Methods. Patients ranged in age from 50 to 81 years. They presented with degenerative Grade I (3- to 14-mm) spondylolisthesis and lumbar stenosis without gross instability (< 3 nun of motion a( the level of subluxation). Those ill whom previous surgery had been performed at the level of subluxation were excluded. Each patient completed Oswestry Disability Index (ODI) and Short Form-36 (SF-36) questionnaires preoperatively and at 6 to 12 month postoperatively. Some patients Underwent decompression alone (20 cases), whereas others underwent decompression and posterolateral instrumentation-assisted fusion (14 cases), at the treating surgeon's discretion. Baseline demographic data. radiographic features, and ODI and SF-36 scores were similar in both groups. The 1-year fusion rate was 93%. Both forms of surgery independently improved outcome compared with baseline status, based on ODI and SF-36 physical component summary (PCS) results (p < 0.001). Decompression combined with fusion led to an improvement in ODI scores of 27.5 points, whereas decompression alone was associated with a 13.6-point increase (p = 0.02). Analysis of the SF-36 PCS data also demonstrated a significant intergroup difference (p = 0.003) Conclusions. Surgery substantially improved 1-year outcomes based on established outcomes instruments in patients with Grade I spondylolisthesis and stenosis. Fusion was associated with greater functional improvement. C1 Yale Univ, Dept Neurosurg, Greenwich Hosp, Sch Med, Greenwich, CT 06830 USA. Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA. Univ Illinois, Dept Neurosurg, Chicago, IL 60680 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Lahey Clin Fdn, Dept Neurosurg, Burlington, MA USA. Rhode Isl Hosp, Dept Neurosurg, Providence, RI 02903 USA. RP Ghogawala, Z (reprint author), Yale Univ, Dept Neurosurg, Greenwich Hosp, Sch Med, 75 Holly Hill Rd, Greenwich, CT 06830 USA. EM zoher.ghogawala@yale.edu NR 31 TC 58 Z9 65 U1 1 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD OCT PY 2004 VL 1 IS 3 BP 267 EP 272 DI 10.3171/spi.2004.1.3.0267 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 888VJ UT WOS:000226402000004 PM 15478364 ER PT J AU Dodson, BB AF Dodson, BB TI Management of mandibular third molar extraction sites to prevent periodontal defects SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID GUIDED TISSUE REGENERATION; DRIED BONE ALLOGRAFTS; 3RD MOLAR SURGERY; CLINICAL-EVALUATION; OSSEOUS DEFECTS; INTRABONY DEFECTS; SURGICAL REMOVAL; GTR TREATMENT; FLAP DESIGN; 2ND MOLARS AB Purpose: Persistent periodontal defects on the distal aspect of the mandibular second molar (M2) is a reported complication of mandibular third molar (M3) extraction. The purpose of this study was to measure the efficacy of demineralized bone powder (DBP) or guided-tissue regeneration therapy (GTR therapy) in preventing periodontal defects on the distal aspect of the M2 following M3 extraction. Materials and Methods: We implemented a single-blind, randomized, controlled clinical trial composed of a sample of subjects greater than or equal to 26 years of age who required extraction of bilateral M3s. The primary predictor variable was treatment group. Each subject was randomly assigned to receive either DBP or GTR therapy. Within subjects, 1 M3 site was randomly selected to be the experimental site and the opposite M3 served as a control and was permitted to heal without intervention. The primary outcome variable was the change in attachment levels (AL) and probing depths (PD) on the disto-buccal aspect of M2 between T-0 (immediate preoperatively) and T-4 (26 weeks postoperatively). Appropriate sample size estimates, descriptive, bivariate, and multivariate statistics were computed. Results: Twelve subjects in the DBP group and 12 subjects in the GTR-therapy group completed the study. For both treatment and control sites, between To and T4, there were statistically significant improvements in AL (greater than or equal to 2.2 mm; P < .001) and PD (greater than or equal to 2.6 mm; P < .001). Within-subjects comparisons showed no significant differences in AL or PD between treatment and control M3 sites (P greater than or equal to .3) at T-0 or T-4. Conclusion: The results of this study suggest that attachment levels and probing depths improve after M3 removal. In this sample, DBP or GTR therapy did not offer predictable benefit over no treatment. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dodson, BB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 48 TC 3 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2004 VL 62 IS 10 BP 1213 EP 1224 DI 10.1016/j.joms.2004.06.035 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 860WF UT WOS:000224373800008 ER PT J AU Troulis, MJ AF Troulis, MJ TI Endoscopic open reduction and internal rigid fixation of subcondylar fractures SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID MANDIBULAR CONDYLAR PROCESS; VERTICAL RAMUS OSTEOTOMY; CLOSED REDUCTION; REPAIR C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM Mtroulis@partners.org NR 24 TC 22 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2004 VL 62 IS 10 BP 1269 EP 1271 DI 10.1016/j.joms.2004.04.016 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 860WF UT WOS:000224373800016 PM 15452816 ER PT J AU Mularski, R Curtis, JR Osborne, M Engelberg, RA Ganzini, L AF Mularski, R Curtis, JR Osborne, M Engelberg, RA Ganzini, L TI Agreement among family members in their assessment of the quality of dying and death SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE death; quality of dying; outcome assessment; quality of health care; quality indicators; health care; end-of-life care; family; proxy; terminal care; attitude to death ID END-OF-LIFE; ILL HOSPITALIZED-PATIENTS; INTENSIVE-CARE UNITS; PROXY RESPONDENTS; CANCER-PATIENTS; CRITICALLY ILL; SYMPTOM BURDEN; DECISIONS; ILLNESS; OLDER AB Improving end-of-life care requires accurate indicators of the quality of dying. The purpose of this study was to measure the agreement among family members who rate a loved one's dying experience. We administered the Quality of Dying and Death instrument to 94 family members of 38 patients who died in the intensive care unit. We measured a quality of dying score of 60 out of 100 points and found moderate agreement among family members as measured by an intraclass correlation coefficient (ICC) of 0.44. Variability on individual items ranged from an ICC of 0.15 to 1.0. Families demonstrated more agreement on frequencies of events (ICC 0.54) than, on determinations of quality (ICC 0.32). These findings reveal important variability among family raters and suggest that until the variability is understood, multiple raters may generate more comprehensive end-of-life data and may more accurately reflect the quality of dying and death. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Oregon Hlth Sci Univ, Dept Psychiat, Div Mental Hlth, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Mularski, R (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Mailcode 111G, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [5 M01 RR00334] NR 49 TC 43 Z9 43 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2004 VL 28 IS 4 BP 306 EP 315 DI 10.1016/j.jpainsymman.2004.01.008 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 864SU UT WOS:000224654000003 PM 15471648 ER PT J AU Hartnick, CJ Anupindi, SA Fan, CM Ryan, D Haver, K AF Hartnick, CJ Anupindi, SA Fan, CM Ryan, D Haver, K TI Fluoroscopic-guided balloon dilation of tracheal stenosis in a 26-week premature infant SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Dept Pediat Surg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Dept Pediat Pulm, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2004 VL 145 IS 4 BP 566 EP 566 DI 10.1016/j.jpeds.2004.04.008 PG 1 WC Pediatrics SC Pediatrics GA 861LH UT WOS:000224417500030 PM 15480388 ER PT J AU Staretz, LR Otomo-Corgel, J Lin, JI AF Staretz, LR Otomo-Corgel, J Lin, JI TI Effects of intravenous midazolam and diazepan on patient response, percentage of oxygen saturation, and hemodynamic factors during periodontal surgery SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE anesthesia; intravenous; conscious sedation; diazepam/therapeutic use; double-blind method; hemodynamics; midazolam/therapeutic use; periodontal diseases/surgery ID WATER-SOLUBLE BENZODIAZEPINE; LOCAL-ANESTHESIA; CONSCIOUS SEDATION; IV SEDATION; INDUCTION; RECOVERY; GASTROSCOPY; FENTANYL; MALEATE; AGENTS AB Background: The purpose of this double-masked study was to evaluate effects of intravenous sedation (IVS) using midazolam or diazepam during periodontal procedures on patient recall, psychomotor response, oxygen saturation, and hemodynamic factors. Methods: Seventeen patients received either two or three scheduled periodontal surgeries under IVS with midazolam, diazepam, or placebo control. Patients were monitored throughout the procedure for hemodynamic variables, percent oxygen saturation, level of recall of common objects presented at baseline, and psychomotor function via the perceptual speed test (PST). Results: Fifteen patients completed the study with average titrated dosages of 3.3 and 12.1 mg for midazolam and diazepam, respectively. Within the limitations of the study, there were few differences observed between the drugs with regard to hemodynamic variables, oxygen saturation, and overall percentage of objects recalled by patients sedated with either drug. However, midazolam was found to cause a greater incidence of amnesia lasting up to 30 minutes when compared to placebo. Patients on diazepam required an average of 15 minutes longer to recover accuracy as measured by the PST. Conclusions: The results suggest that diazepam and midazolam each may have advantages for IVS. In procedures lasting over 45 minutes, diazepam appears to be more clinically advantageous including a wider margin of safety during titration and gradual recovery. IAidazolam may be used for shorter procedures for faster onset of action, predictable amnesic effects, and relatively rapid recovery. C1 Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Wadsworth VA Med Ctr, Sect Periodont, Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Lin, JI (reprint author), W Los Angeles Vet Affairs Wadsworth VA Med Ctr, Sect Periodont, Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jilin@ucla.edu NR 44 TC 3 Z9 3 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 2004 VL 75 IS 10 BP 1319 EP 1326 DI 10.1902/jop.2004.75.10.1319 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 866KJ UT WOS:000224772100004 PM 15562908 ER PT J AU Raines, DE Gioia, F Claycomb, RJ Stevens, RJ AF Raines, DE Gioia, F Claycomb, RJ Stevens, RJ TI The N-methyl-D-aspartate receptor inhibitory potencies of aromatic inhaled drugs of abuse: Evidence for modulation by cation-pi interactions SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 11-15, 2003 CL SAN FRANCISCO, CA SP Amer Soc Anesthesiologists ID NICOTINIC ACETYLCHOLINE-RECEPTOR; NONHALOGENATED ALKANE ANESTHETICS; VOLATILE GENERAL-ANESTHETICS; GAMMA-AMINOBUTYRIC-ACID; GATED ION CHANNELS; ELECTROSTATIC INTERACTIONS; LIGAND RECOGNITION; XENOPUS OOCYTES; ALCOHOL CUTOFF; SIDE-CHAINS AB Benzene and several close structural analogs are inhaled drugs of abuse with general anesthetic activity. By virtue of their pi electron clouds, they may engage in attractive electrostatic interactions with cationic atomic charges on protein targets. In this study, we tested the hypothesis that inhaled drugs of abuse inhibit human N-methyl-D-aspartate ( NMDA) receptors with potencies that correlate with their abilities to engage in cation-pi interactions. Electrophysiological techniques were used to define the NR1/NR2B NMDA receptor inhibitory concentrations of volatile benzene analogs, and computer modeling was used to quantify their abilities to engage in cation-pi interactions and their molecular volumes. In addition, each compound's octanol/gas partition coefficient (a measure of hydrophobicity) was quantified. All 18 compounds inhibited human NR1/NR2B NMDA receptors reversibly and in a concentration-dependent manner. NMDA receptor inhibitory potency correlated strongly with the ability to engage in cation-pi interactions, weakly with hydrophobicity, and was independent of molecular volume. This is consistent with the hypothesis that cation-pi interactions enhance the binding of inhaled drugs of abuse to the NMDA receptor and suggests that the receptor binding site(s) for these drugs possesses significant cationic character. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM draines@partners.org FU NIGMS NIH HHS [GM61927] NR 48 TC 27 Z9 27 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2004 VL 311 IS 1 BP 14 EP 21 DI 10.1124/jpet.104.069930 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 854IK UT WOS:000223896100003 PM 15166258 ER PT J AU Cooper, GS Parks, CG Treadwell, EL Clair, EWS Gilkeson, GS Dooley, MA AF Cooper, GS Parks, CG Treadwell, EL Clair, EWS Gilkeson, GS Dooley, MA TI Occupational risk factors for the development of systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; occupation; mercury; solvents; pesticides ID DENTAL LABORATORY TECHNICIANS; SOUTHEASTERN UNITED-STATES; MRL-+/+ MICE; AUTOIMMUNE-RESPONSE; SOLVENT EXPOSURE; MERCURY; DISEASE; MELATONIN; CONCORDANCE; SCLERODERMA AB Objective. There have been few studies of occupational exposures and systemic lupus erythematosus (SLE). We examined the association between the risk of SLE and occupational exposures (mercury, solvents, and pesticides), specific jobs (ever worked in teaching, healthcare, and cosmetology), and working night or rotating shifts. Methods. Patients with recently diagnosed SLE (n = 265) were recruited through 4 university based and 30 community based rheumatology practices in North Carolina and South Carolina, USA. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included ail in-person interview with detailed farming and work histories. Results. Associations were seen with self-reported occupational exposure to mercury (OR 3.6, 95% CI 1.3, 10.0), mixing pesticides for agricultural work (OR 7.4, 95% CI 1.4, 40.0), and among dental workers (OR 7.1, 95% CI 2.2, 23.4). Although these associations were fairly strong and statistically significant, the prevalence of these exposures was very low and thus these estimates are based on a small number of exposed cases and controls. Weaker associations were seen between SLE and shift work (OR 1.6, 95% CI 0.99, 2.7) and among healthcare workers with patient contact (OR 1.7, 95% CI 0.99, 2.9). There was no association of SLE with use of solvents or among teachers or cosmetologists. Conclusion. This study reveals the potential contribution of occupational exposures to the development of SLE, and highlights some exposures and experiences that should be examined in other studies using more extensive exposure assessment techniques and in experimental studies of autoimmunity. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Durham, NC 27709 USA. EM cooper1@niehs.nih.gov OI Parks, Christine/0000-0002-5734-3456 NR 32 TC 81 Z9 83 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2004 VL 31 IS 10 BP 1928 EP 1933 PG 6 WC Rheumatology SC Rheumatology GA 860FC UT WOS:000224326900011 PM 15468355 ER PT J AU Lewis, MA Butterfield, RM Darbes, LA Johnston-Brooks, C AF Lewis, MA Butterfield, RM Darbes, LA Johnston-Brooks, C TI The conceptualization and assessment of health-related social control SO JOURNAL OF SOCIAL AND PERSONAL RELATIONSHIPS LA English DT Article DE health; marriage; measurement; qualitative methodology; social control ID PSYCHOLOGICAL DISTRESS; BEHAVIORS; SUPPORT; FAMILY; PERSPECTIVE; STRATEGIES; MARRIAGE; SMOKING; GENDER; POWER AB Three studies examined the conceptualization and assessment of health-related social control in marriage. Using a sample of 100 couples, Study 1 tested the idea that social control is best thought of as the exercise of power and control in close relationships. Results did not support this conceptualization or assessment of health-related social control in marriage. Based on these results, Study 2 collected qualitative data from husbands and wives via focus groups to explore the use of social control tactics that couples use to change health behavior. Results indicated that many tactics reported by spouses are not contained in the social influence literature, and that the exercise of social control in marriage may best be characterized of as an interdependent communally oriented process between spouses. Using another sample of 109 married couples, Study 3 tested the reliability and validity of a measure developed from the qualitative data. Results indicated the new measure of health-related social control tactics evidenced better reliability and validity than the measure used in Study 1. C1 Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Denver, CO USA. RP Lewis, MA (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, CB 7440, Chapel Hill, NC 27599 USA. EM megan.lewis@unc.edu NR 39 TC 48 Z9 48 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0265-4075 J9 J SOC PERS RELAT JI J. Soc. Pers. Relatsh. PD OCT PY 2004 VL 21 IS 5 BP 669 EP 687 DI 10.1177/0265404045893 PG 19 WC Communication; Family Studies; Psychology, Social SC Communication; Family Studies; Psychology GA 866FE UT WOS:000224758400007 ER PT J AU Trbovich, AM Martinelle, N O'Neill, FH Pearson, EJ Donahoe, PK Sluss, PM Teixeira, J AF Trbovich, AM Martinelle, N O'Neill, FH Pearson, EJ Donahoe, PK Sluss, PM Teixeira, J TI Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP and Mullerian inhibiting substance SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Mullerian inhibiting substance; Cyp17; Leydig cells; 5 alpha-reductase ID HUMAN P450C17; 17,20-LYASE ACTIVITY; ANDROGEN SYNTHESIS; SEXUAL DEVELOPMENT; TRANSGENIC MICE; MOUSE OVARY; IN-VITRO; HORMONE; EXPRESSION; GROWTH AB In addition to causing Mullerian duct regression in fetal males, Mullerian inhibiting substance (MIS) inhibits the expression of the bifunctional cytochrome P450, C17 hydroxylase/C17-20 lyase (Cyp17), the enzyme that catalyzes the committed step in sex steroid synthesis. To investigate the paracrine effects of MIS on steroidogenic activity, we have performed assays with microsomes from mouse MA-10 Leydig cells. With microsomes from untreated MA-10 cells, progesterone was largely metabolized by 5alpha-reductase and subsequently converted by 3-keto steroid reductases to allopregnanolone and epiallopregnanolone. Addition of cAMP to the cells shifted microsomal steroid production to the Cyp17 product androstenedione and its 5alpha,3beta-reduced form, epiandrosterone. Microsomes from MIS-treated cells were less active with the progesterone substrate than those of untreated cells but co-treatment of the cells with both MIS and cAMP mitigated the cAMP-induced shift of the microsomes to androstenedione production. Quantitative analyses of steroid production by Cyp17 showed that cAMP decreased the amount of 17-hydroxyprogesterone produced relative to the androstenedione, suggesting that cAMP signaling lowers the efficiency of the Cyp17 hydroxylase activity or else increases the efficiency of its lyase activity. Addition of MIS to the cAMP-treated cells partially reversed this effect, as well. These results indicate that cAMP induces MA-10 cells to switch from producing 5alpha-reduced progesterone metabolites to producing androstenedione and its metabolites by increasing Cyp17 expression and its relative lyase activity, both of which are inhibited by MIS. (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs WRN 1024, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Karolinska Inst, Astrid Lindgren Childrens Hosp, Pediat Endocrinol Unit, Dept Woman & Child Hlth, Stockholm, Sweden. Massachusetts Gen Hosp, Reproduct Endocrine Sci Ctr, Boston, MA USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs WRN 1024, 32 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NCI NIH HHS [R29 CA079459, R29 CA079459-05, R29-CA79459]; NICHD NIH HHS [U54 HD28138] NR 43 TC 14 Z9 15 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2004 VL 92 IS 3 BP 199 EP 208 DI 10.1016/j.jsbmb.2004.07.002 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 883KC UT WOS:000226009000009 PM 15555913 ER PT J AU O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Ko, CY AF O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Ko, CY TI A report card on outcomes for surgically treated gastrointestinal cancers: Are we improving? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE gastrointestinal cancer; esophageal; gastric; small bowel; colorectal; hepatobiliary; population-based; survival; report card; inpatient mortality ID SPECIAL SECTION; NATION; MORTALITY; TRENDS; US AB Introduction. Longitudinal analyses of cancer registries provide an opportunity for population-based explanations of epidemiology and survival-related outcomes. This study used two population-based data sets to report on nine surgery-related cancers over the past three decades. Materials and methods. Using the SEER cancer database (1973-1999), all patients (>18 years old) with adenocarcinoma of esophagus, gastric, biliary system, pancreas, small bowel, colon, rectum; esophageal squamous cell carcinoma (ESC), or hepatocellular (HCC) carcinoma (n = 379,640) were analyzed. Changes in incidence rates, stage at diagnosis, and 5-year cancer and stage-specific survivals were determined. A separate database, the California inpatient database (1990-2000), was concurrently used to evaluate inpatient mortality after surgical resection (n = 34,057). Results. Incidence rates increased for three cancers (esophageal, HCC, small bowel); decreased for three (rectal, gastric, ESC); and stayed constant for three (biliary, pancreatic, colon). More patients presented with local/regional disease in the 1990s versus 1970s for eight tumors (except small bowel, P < 0.05). Five-year overall survival improved for all but small bowel (P < 0.05); and local stage survival was improved for all except small bowel and biliary (P < 0.05). Finally, inpatient mortality rates improved significantly for liver, esophageal, pancreatic, and gastric resections (P < 0.05) over the past decade. Conclusions. For these nine surgically treated cancers, we are detecting disease at earlier and therefore more treatable stages, and surgical care and outcomes also appear to have improved. Continued reexamination of longitudinal trends of surgically relevant outcomes is important for future improvement of surgical care. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Room 72-215 CHS, Los Angeles, CA 90095 USA. EM jbocjboc@hotmail.com NR 16 TC 13 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2004 VL 121 IS 2 BP 214 EP 221 DI 10.1016/j.jss.2004.04.002 PG 8 WC Surgery SC Surgery GA 866EU UT WOS:000224757400008 PM 15501461 ER PT J AU Voss, SE Shera, CA AF Voss, SE Shera, CA TI Simultaneous measurement of middle-ear input impedance and forward/reverse transmission in cat SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EVOKED OTOACOUSTIC EMISSIONS; PRESSURE MEASUREMENTS; ACOUSTIC-IMPEDANCE; TYMPANIC MEMBRANE; COCHLEA; MECHANICS; WINDOWS; DIFFERENCE; MODEL AB Reported here is a technique for measuring forward and reverse middle-ear transmission that exploits distortion-product otoacoustic emissions (DPOAEs) to drive the middle ear "in reverse" without opening the inner ear. The technique allows measurement of DPOAEs, middle-ear input impedance, and forward and reverse middle-ear transfer functions in the same animal. Intermodulation distortion in the cochlea generates a DPOAE at frequency 2f(1) - f(2) measurable in both ear-canal pressure and the velocity of the stapes. The forward transfer function is computed from stapes velocities and corresponding ear-canal pressures measured at the two primary frequencies; the reverse transfer function is computed from velocity and pressure measurements at the DPOAE frequency. Middle-ear input impedance is computed from ear-canal pressure measurements and the measured Thevenin equivalent of the sound-delivery system. The technique was applied to measure middle-ear characteristics in anesthetized cats with widely opened middle-ear cavities (0.2-10 kHz). Stapes velocity was measured at the incudo-stapedial joint. Results on five animals are reported and compared with a published middle-ear model. The measured forward transfer functions and input impedances generally agree with previous measurements, and all measurements agree qualitatively with model predictions. The reverse transfer function is shown to depend on the acoustic load in the car canal, and the measurements are used to compute the round-trip middle-ear gain and delay. Finally, the measurements are used to estimate the parameters of a two-port transfer-matrix description of the cat middle ear. (C) 2004 Acoustical Society of America. C1 Smith Coll, Picker Engn Program, Northampton, MA 01063 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Audit Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA. EM svoss@email.smith.edu FU NIDCD NIH HHS [R01 DC003687, R01 DC03687] NR 44 TC 22 Z9 23 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2004 VL 116 IS 4 BP 2187 EP 2198 DI 10.1021/1.1785832 PN 1 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 864TK UT WOS:000224655600034 PM 15532651 ER PT J AU Hood, KK Baptista-Neto, L Beasley, PJ Lobis, R Pravdova, I AF Hood, KK Baptista-Neto, L Beasley, PJ Lobis, R Pravdova, I TI Case study: Severe self-injurious behavior in comorbid Tourette's disorder and OCD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE self-injurious behavior; Tourette's disorder; obsessive-compulsive disorder ID OBSESSIVE-COMPULSIVE DISORDER; GILLES; CLOMIPRAMINE AB This case report describes the successful treatment of severe self-injurious behavior in a 16-year-old adolescent with Tourette's disorder and obsessive-compulsive disorder. Treatment is described from initial presentation to the emergency department for severe self-inflicted oral lacerations through discharge from the inpatient psychiatric service. Modes of treatment included emergent medical intervention, intensive care services, psychopharmacology, and psychological services. The collection of treatment modalities implemented by this multidisciplinary team may serve as a guide to other health care professionals when severe self-injurious behavior is the presenting problem. C1 Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Childrens Hosp, Boston, MA USA. RP Hood, KK (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM korey.hood@joslin.harvard.edu NR 23 TC 10 Z9 10 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2004 VL 43 IS 10 BP 1298 EP 1303 DI 10.1097/01.chi.0000134492.80925.96 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 856KP UT WOS:000224044400022 PM 15381898 ER PT J AU Marra, DE Mckee, PH Nghiem, P AF Marra, DE Mckee, PH Nghiem, P TI Tissue eosinophils, and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; DIAGNOSIS AB Graft-versus-host disease (GvHD) is a frequent and serious complication of bone-marrow transplantation (BMT), and carries a high morbidity and mortality if not promptly recognized and treated. The rash of acute GvHD is often difficult to distinguish clinically from a drug eruption, and skin biopsies are often performed in an attempt to render a diagnosis. Histologically, eosinophils are classically associated with hypersensitivity reactions, and their presence in inflamed tissue is considered suggestive of a drug-induced dermatitis. We present 3 cases of acute exanthema in BMT recipients in whom the presence of eosinophils on skin biopsy specimen led to an initial diagnosis of drug eruption over GvHD. As a result, these patients experienced delays in the institution of definitive immunosuppressive therapy for GvHD. We review the growing literature suggesting that no single or combined histologic feature, including tissue eosinophils, is useful in differentiating GvHD from drug eruptions in BMT recipients. Indeed, in most cases, the cause of a new-onset blanchable erythematous rash in a BMT recipient is most accurately determined by close examination and follow-Lip of the clinical features without a skin biopsy. C1 Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nghiem, P (reprint author), Dana Farber Canc Inst, Ctr Cutaneous Oncol, 44 Binney St, Boston, MA 02115 USA. EM pnghiem@partners.org RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X NR 19 TC 29 Z9 31 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2004 VL 51 IS 4 BP 543 EP 546 DI 10.1016/j.jaad.2004.02.019 PG 4 WC Dermatology SC Dermatology GA 859RY UT WOS:000224286800005 PM 15389188 ER PT J AU Adams, AE Zwicker, J Curiel, C Kadin, ME Falchuk, KR Drews, R Kupper, TS AF Adams, AE Zwicker, J Curiel, C Kadin, ME Falchuk, KR Drews, R Kupper, TS TI Aggressive cutaneous T-cell lymphomas after TNF alpha blockade SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; MYCOSIS-FUNGOIDES; CD30; RECEPTOR; DISEASE; MECHANISMS; THERAPY; TRAF2 AB Pharmacologic blockade of TNFalpha has been a highly effective approach to treating several immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis.(1,2,3) Both etanercept, the recombinant extracellular domain of the tumor necrosis factor receptor 2 (TNFR2), and infliximab, a humanized murine antibody, bind TNFalpha and block its interaction with cell surface receptors. Recently, it has become clear that blockade of TNFalpha action is profoundly immunosuppressive, and may result in reactivation of tuberculosis and histoplasmosis, as well as the emergence of B-cell lymphomas.(4,5,6) In this report, we describe two cases of cutaneous and systemic T-cell lymphoma that progressed rapidly in the setting of TNFalpha blockade. Both cases were characterized by rapid onset, a fulminant clinical course with extensive cutaneous and systemic involvement, and death within months of diagnosis. C1 Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dept Med, Boston, MA USA. RP Kupper, TS (reprint author), 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM tskupper@partners.org NR 20 TC 51 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2004 VL 51 IS 4 BP 660 EP 662 DI 10.1016/j.jaad.2004.03.047 PG 3 WC Dermatology SC Dermatology GA 859RY UT WOS:000224286800024 PM 15389210 ER PT J AU Bryson, CL Smith, NL Kuller, LH Chaves, PHM Manolio, TA Lewis, W Boyko, EJ Furberg, CD Psaty, BM AF Bryson, CL Smith, NL Kuller, LH Chaves, PHM Manolio, TA Lewis, W Boyko, EJ Furberg, CD Psaty, BM TI Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hypertension treatment; heart failure; alpha-1 antagonist; thiazide ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; SYSTEMIC HYPERTENSION; CARDIOVASCULAR EVENTS; BLOOD-PRESSURE; OLDER PERSONS; DOXAZOSIN; HEALTH; CHLORTHALIDONE; ATENOLOL AB Objectives: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists. Design: Prospective cohort study. Setting: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina. Participants: A total of 5,888 community-dwelling subjects aged 65 and older. Measurements: Adjudicated incident CHF. Results: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk. Conclusion: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this. C1 VA Puget Sound HSR&D, Seattle VAMC, Seattle, WA 98108 USA. VA Puget Sound Healthcare Syst, Epidemiol Res & Informat Ctr, VAMC, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RP Bryson, CL (reprint author), VA Puget Sound HSR&D, Seattle VAMC, MS 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM cbryson@u.washington.edu FU NHLBI NIH HHS [N01-HC-85081, N01-HC-85086, N01-HC-85082, N01-HC-35129, N01-HC-85085, N01-HC-85079, N01-HC-85083, N01-HC-15103, N01-HC-85084, N01-HC-85080] NR 21 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2004 VL 52 IS 10 BP 1648 EP 1654 DI 10.1111/j.1532-5415.2004.52456.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 855TU UT WOS:000223998300007 PM 15450040 ER PT J AU Gupta, SK Lamont, EB AF Gupta, SK Lamont, EB TI Patterns of presentation, diagnosis, and treatment in older patients with colon cancer and comorbid dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; colon cancer; elderly; treatment; SEER-Medicare ID POSTOPERATIVE ADJUVANT THERAPY; ALZHEIMERS-DISEASE; MEDICARE CLAIMS; FLUOROURACIL; HEALTH; CHEMOTHERAPY; EPIDEMIOLOGY; SURVIVAL; STAGE; COST AB Objectives: To estimate patterns of colon cancer presentation, diagnosis, and treatment according to history of dementia using National Cancer Institute (NCI) Surveillance, Epidemiology, and End-Result (SEER) Medicare data. Design: Population-level cohort study. Setting: NCI's SEER-Medicare database. Participants: A total of 17,507 individuals aged 67 and older with invasive colon cancer (Stage I-IV) were identified from the 1993-1996 SEER file. Medicare files were evaluated to determine which patients had an antecedent diagnosis of dementia. Measurements: Parameters relating to the cohort's patterns of presentation and care were estimated using logistic regressions. Results: The prevalence of dementia in the cohort of newly diagnosed colon cancer patients was 6.8% (1,184/17,507). Adjusting for possible confounders, dementia patients were twice as likely to have colon cancer reported after death (i.e., autopsy or death certificate) (adjusted odds ratio (AOR)=2.31, 95% confidence interval (CI)=1.79-3.00). Of those diagnosed before death (n=17,049), dementia patients were twice as likely to be diagnosed noninvasively than with tissue evaluation (i.e., positive histology) (AOR=2.02 95% CI=1.63-2.51). Of patients with Stage I -III disease (n=12,728), patients with dementia were half as likely to receive surgical resection (AOR=0.48, 95% CI=0.33-0.70). Furthermore, of those with resected Stage III colon cancer (n=3,386), dementia patients were 78% less likely to receive adjuvant 5-fluorouracil (AOR=0.22, 95% CI=0.13-0.36). Conclusion: Although the incidences of dementia and cancer rise with age, little is known about the effect of dementia on cancer presentation and treatment. Elderly colon cancer patients are less likely to receive invasive diagnostic methods or curative-intent therapies. The utility of anticancer therapies in patients with dementia merits further study. C1 Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Sect Geriatr, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Gupta, SK (reprint author), Univ Chicago, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM sgupta@medicine.bsd.uchicago.edu FU NCI NIH HHS [K07 CA093892, K07 CA93892] NR 50 TC 55 Z9 55 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2004 VL 52 IS 10 BP 1681 EP 1687 DI 10.1111/j.1532-5415.2004.52461.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 855TU UT WOS:000223998300012 PM 15450045 ER PT J AU Ruckdeschel, K Katz, IR AF Ruckdeschel, K Katz, IR TI Care of dementia and other mental disorders in assisted living facilities: New research and borrowed knowledge SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID NURSING-HOMES C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Ruckdeschel, K (reprint author), Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. FU PHS HHS [P3066270] NR 6 TC 3 Z9 3 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2004 VL 52 IS 10 BP 1771 EP 1773 DI 10.1111/j.1532-5415.2004.52476.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 855TU UT WOS:000223998300028 PM 15450061 ER PT J AU Podolsky, SH AF Podolsky, SH TI Biomedical platforms: Realigning the normal and the pathological in late-twentieth-century medicine. SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, SH (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 EI 1468-4373 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD OCT PY 2004 VL 59 IS 4 BP 602 EP 604 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 849FM UT WOS:000223524100010 ER PT J AU Lee, AYY Gent, M Julian, JA Bauer, KA Eriksson, BI Lassen, MR Turpie, AGG AF Lee, AYY Gent, M Julian, JA Bauer, KA Eriksson, BI Lassen, MR Turpie, AGG TI Bilateral vs. ipsilateral venography as the primary efficacy outcome measure in thromboprophylaxis clinical trials: a systematic review SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE deep vein thrombosis; thromboprophylaxis; venography; venous thromboembolism ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; TOTAL HIP-REPLACEMENT; TOTAL KNEE REPLACEMENT; DOUBLE-BLIND TRIAL; VENOUS THROMBOSIS; ELECTIVE HIP; UNFRACTIONATED HEPARIN; RANDOMIZED TRIAL; GENERAL-ANESTHESIA AB Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standard efficacy outcome measure in clinical trials of tbromboprophylaxis in major orthopedic surgery. It is uncertain whether performing bilateral venography offers any real advantage over venography of the operated leg alone. This study was undertaken to determine the risk of isolated contralateral deep vein thrombosis (DVT) following major orthopedic surgery and to evaluate whether bilateral venography. rather than venography on the operated leg alone, offers any gain in DVT detection and, thereby, improves efficiency in clinical study design. A systematic review of prospective Studies that reported DVT incidence as the primary efficacy outcome based on mandatory bilateral venography in patients undergoing elective hip or knee arthroplasty or hip fracture repair was conducted. Based on the use of bilateral venography as a primary efficacy outcome measure, the incidence of any DVT is 16.7% following total hip replacement, 18.8% after hip fracture repair, and 33.8% after total knee replacement. While DVT risk in the operated leg varies depending on the type of surgery, the risk of isolated DVT in the non-operated leg is approximately 4% to 5% in all three procedures. By increasing the detection of any DVT, the use of bilateral venography reduces required sample size by 16% to 25% compared to ipsilateral venography. In clinical trials evaluating the efficacy of thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the risk of undiagnosed DVT in the non-operated leg and improves the efficiency of study design by substantially reducing the sample size requirement. C1 Henderson Gen Hosp, Hamilton Hlth Sci, Henderson Res Ctr, Hamilton, ON L8V 1C3, Canada. McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4L8, Canada. Boston Healthcare Syst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Sahlgrens Univ Hosp, Dept Orthoped, S-41345 Gothenburg, Sweden. Hoersholm Hosp, Spine Clin, Dept Clin Res, Copenhagen, Denmark. RP Lee, AYY (reprint author), Henderson Gen Hosp, Hamilton Hlth Sci, Henderson Res Ctr, 711 Concess St, Hamilton, ON L8V 1C3, Canada. EM alee@mcmaster.ca NR 54 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2004 VL 2 IS 10 BP 1752 EP 1759 DI 10.1111/j.1538-7836.2004.00915.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 859TE UT WOS:000224290000013 PM 15456486 ER PT J AU Phillips, JE Lord, ST Gilbert, GE AF Phillips, JE Lord, ST Gilbert, GE TI Fibrin stimulates platelets to increase factor VIIIa binding site expression SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE factor VIII; fibrin; GPIIbIIIa; platelets ID FACTOR-X ACTIVATION; PHOSPHATIDYL-L-SERINE; SCOTT SYNDROME; INTEGRIN ALPHA(IIB)BETA(3); AMINOPHOSPHOLIPID EXPOSURE; TYROSINE PHOSPHORYLATION; MICROPARTICLE FORMATION; RECOMBINANT FIBRINOGEN; PROCOAGULANT ACTIVITY; THROMBIN GENERATION AB Factor (F)VIII functions as an enzymatic cofactor on the membranes of stimulated platelets. However, thrombin stimulates platelets to express only a small number of binding sites for FVIII. We wished to determine whether molecules that are likely to be present in a developing thrombus stimulate platelets to up-regulate FVIII binding site expression. Flow cytometry was utilized to measure binding of fluoresce-inlabeled FVIIIa to activated platelets and a FXase assay was utilized to measure platelet-dependent function. Various agonists as well as normal and mutant fibrinogens and fibrin were evaluated as co-stimuli. Thrombin-stimulated platelets expressed 214 +/- 67 binding sites for thrombin-activated FVIII (FVIIIa) and none of the established soluble agonists enhanced binding site exposure. However, the presence of 5 mug mL(-1) fibrin increased the number of FVIIIa binding sites/platelet three- to eight-fold (1470 +/- 130, range 600-1800) with a parallel increase in platelet-based FXase assay. Binding site upregulation was not stimulated by fibrinogen and was blocked by inhibitors of GPIIbIIIa. Mutant fibrin lacking the gamma-chain C-terminal four residues was ineffective while fibrin with altered RGD sequences did stimulate expression of FVIIIa binding sites indicating that co-stimulation is mediated by the fibrin 7-chain termini. Fibrin-enhanced expression of FVIIIa binding sites was not supported by D364H fibrin, which does not aggregate normally, and was blocked by the GPRP peptide, which inhibits fibrin polymerization. Polymerized fibrin can function as a platelet co-stimulus, up-regulating expression of binding sites for FVIIIa. C1 Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Ctr, Dept Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM ggilbert@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL57867, R01 HL310481, P01 HL42443] NR 45 TC 10 Z9 10 U1 1 U2 1 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2004 VL 2 IS 10 BP 1806 EP 1815 DI 10.1111/j.1538-7836.2004.00919.x PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 859TE UT WOS:000224290000020 PM 15456493 ER PT J AU Ray, KK Cannon, CP AF Ray, KK Cannon, CP TI Pathological changes in acute coronary syndromes: The role of statin therapy in the modulation of inflammation, endothelial function and coagulation SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Review DE statins; inflammation; endothelial function; coagulation ID C-REACTIVE PROTEIN; COA REDUCTASE INHIBITORS; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; TISSUE FACTOR EXPRESSION; ANTIINFLAMMATORY CYTOKINE INTERLEUKIN-10; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE-1; PLASMINOGEN-ACTIVATOR INHIBITOR-1; DENSITY-LIPOPROTEIN CHOLESTEROL AB Considerable progress has been made in our understanding of the pathophysiology of coronary artery disease (CAD), their acute presentations as acute coronary syndromes (ACS) and the role of LDL cholesterol. In particular there is clear evidence that atherosclerosis is far from being a process that leads to an amorphous flow limiting lesion on an angiogram, but rather involves a complex interplay between the endothelium, inflammatory cells and the coagulation cascade occurring throughout the coronary vascular bed. While a culprit flow limiting lesion may be effectively treated by a drug eluting stent or coronary bypass surgery, this will have little impact on the global molecular processes that determine recurrent plaque instability at non-culprit sites. The search for systemic long term therapy, which is safe and effective and reduces the changes in inflammation, endothelial function and thrombosis that are the hallmark of ACS, has pushed statins to the forefront. A number of recent clinical trials have shown the benefits of early statin therapy in the treatment of ACS. In addition to their effects on LDL cholesterol, statins have a number of properties collectively referred to as pleiotropic effects, which enable them to modulate the adverse biological changes that are associated with ACS. The purpose of this review is to acquaint the reader with the biological changes that accompany ACS, highlight how these pathways may be modulated for clinical benefit by statins and identify potential novel targets for future therapy. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ray, KK (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM kkray@partners.org NR 136 TC 25 Z9 27 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2004 VL 18 IS 2 BP 89 EP 101 DI 10.1007/s11239-004-0205-9 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 893NS UT WOS:000226727100003 PM 15789175 ER PT J AU O'Keeffe, T Goldman, RK Mayberry, JC Rehm, CG Hart, RA AF O'Keeffe, T Goldman, RK Mayberry, JC Rehm, CG Hart, RA TI Tracheostomy after anterior cervical spine fixation SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE tracheostomy; anterior; cervical spine; fixation; spinal cord injury; American Spinal Injury Association; (ASIA) ID PERCUTANEOUS DILATIONAL TRACHEOSTOMY; RESPIRATORY COMPLICATIONS; CORD INJURY; INTENSIVE-CARE; DILATATIONAL TRACHEOSTOMY; TRAUMA PATIENTS; FOLLOW-UP; SURGERY; MANAGEMENT; FUSION AB Background: Patients with cervical spine injury may require both anterior cervical spine fusion and tracheostomy, particularly in the setting of associated cervical spinal cord injury (SCI). Despite the close proximity of the two surgical incisions, we postulated that tracheostomy could be safely performed after anterior spine fixation. In addition, we postulated that the severity of motor deficits in patients with cervical spine injury would correlate with the need for tracheostomy. Methods: A retrospective review was undertaken of all adult trauma patients diagnosed with cervical spine fractures or cervical SCI admitted between June 1996 and June 2001 at our university Level I trauma center. Demographic data, severity of neurologic injury based on the classification of the American Spinal Injury Association (ASIA), complications, and use and type of tracheostomy were collected. In the subgroup of patients with unstable cervical spine injury that under-went anterior stabilization and tracheostomy, data regarding timing and technique of these procedures and wound outcomes were also collected. Categorical data were analyzed using X-2 analysis using Yates correction when appropriate, with p < 0.05 considered significant. Results: During this time period, 275 adult survivors were diagnosed with cervical spinal cord or bony injury. Fortyfive percent of patients with SCI (27 of 60) and 14% of patients without SCI (30 of 215) underwent tracheostomy (p < 0.001). Moreover, on the basis of the ASIA classification system, 76% of ASIA A and B patients, 38% of ASIA C patients, 23% of ASIA D patients, and 14% of ASIA E patients were treated with tracheostomy (p < 0.001). In the subgroup that underwent both anterior spine fixation and tracheostomy (n = 17), the median time interval from spine fixation to airway placement was 7 days (interquartile range, 6-10 days), with 71% of these tracheostomies performed percutaneously. No patient developed a wound infection or nonunion as a consequence of tracheostomy placement, and there were no deaths because of complications of either procedure. Conclusions: These data support the safety of tracheostomy insertion 6 to 10 days after anterior cervical spine fixation, particularly in the presence of cervical SCL The presence of severe motor neurologic deficits was strongly associated with the use of tracheostomy in patients with cervical spine injury. Percutaneous tracheostomy, which is our technique of choice, may be advantageous in this setting by virtue of creating only a small wound. The optimal timing and use of tracheostomy in patients with cervical spine injury requires further study. C1 Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Trauma Crit Care Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Orthopaed Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Goldman, RK (reprint author), Oregon Hlth & Sci Univ, Div Gen Surg, 3181 SW Sam Jackson Pk Rd,L223A, Portland, OR 97239 USA. EM goldmanr@ohsu.edu NR 40 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2004 VL 57 IS 4 BP 855 EP 860 DI 10.1097/01.TA.000083006.48501.B2 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 871EN UT WOS:000225112300032 PM 15514542 ER PT J AU Newman, E Kaloupek, DG AF Newman, E Kaloupek, DG TI The risks and benefits of participating in trauma-focused research studies SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE experimental ethics; experimental subjects; posttraumatic stress disorder; risk analysis; risk-benefits analysis; study protocols; disaster ID HEALTH SURVEYS DISTURB; ETHICAL ISSUES; VICTIMS AB Concern about minimizing harm and maximizing benefit has been particularly acute with regard to the scientific study of individuals exposed to potentially traumatic events such as terrorist attack or disaster. This review outlines conceptual and practical issues and summarizes available evidence regarding potential risks and benefits of participation in trauma-related research. Current, limited evidence suggests that most individuals make favorable cost-benefit appraisals regarding their participation. Although a subset of participants report strong negative emotions or unanticipated distress, the majority of these do not regret or negatively evaluate the overall experience. Continuing efforts are needed to identify individuals at risk for unfavorable reactions to research participation. A systematic empirical approach to evaluating participant experience in all human research is recommended. C1 Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Newman, E (reprint author), Univ Tulsa, Dept Psychol, Lorton Hall,600 S Coll Ave, Tulsa, OK 74104 USA. EM elana-newman@utulsa.edu OI Kaloupek, Danny/0000-0002-0795-593X NR 24 TC 107 Z9 107 U1 1 U2 10 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2004 VL 17 IS 5 BP 383 EP 394 DI 10.1023/B:JOTS.0000048951.02568.3a PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 881BI UT WOS:000225838000004 PM 15633917 ER PT J AU Hinton, DE Pham, T Tran, M Safren, SA Otto, MW Pollack, MH AF Hinton, DE Pham, T Tran, M Safren, SA Otto, MW Pollack, MH TI CBT for Vietnamese refugees with treatment-resistant PTSD and panic attacks: A pilot study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder; panic attacks; cognitive-behavior therapy; Vietnamese refugees ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIOR THERAPY; CAMBODIAN REFUGEES; TORTURE; COMBINATION; PREVALENCE; EXPOSURE; VICTIMS AB We examined the feasibility, acceptability, and therapeutic efficacy of a culturally adapted cognitive-behavior therapy (CBT) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder (PTSD) and panic attacks. These patients were treated in two separate cohorts of six with staggered onset of treatment. Repeated measures Group x Time ANOVAs and between-group comparisons indicated significant improvements, with large effect sizes (Cohen's d) for all outcome measures: Harvard Trauma Questionnaire (HTQ; d = 2.5); Anxiety Sensitivity Index (ASI; d = 4.3); Hopkins Symptom Checklist-25 (HSCL-25), anxiety subscale (d = 2.2); and Hopkins Symptom Checklist-25, depression subscale (d = 2.0) scores. Likewise, the severity of (culturally related) headache-and orthostasis-cued panic attacks improved significantly across treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Arbour Counseling Serv, SE Asian Clin, Lowell, MA USA. E Boston Counseling Ctr, SE Asian Clin, East Boston, MA USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu FU NIMH NIH HHS [R01 MH094312, K23 MH066253-05, K23 MH066253] NR 19 TC 85 Z9 89 U1 1 U2 10 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2004 VL 17 IS 5 BP 429 EP 433 DI 10.1023/B:JOTS.0000048956.03529.fa PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 881BI UT WOS:000225838000009 PM 15633922 ER PT J AU Georgian-Smith, D McKee, G Yeh, E Rafferty, EA D'Alessandro, HA Kopans, DB AF Georgian-Smith, D McKee, G Yeh, E Rafferty, EA D'Alessandro, HA Kopans, DB TI The mammary hamartoma - Appreciation of additional imaging characteristics SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE breast; hamartomal; sonography ID INVASIVE DUCTAL CARCINOMA; BREAST HAMARTOMAS; LOBULAR CARCINOMA; IN-SITU; SONOGRAPHY; BENIGN AB Objective. To determine the mammographic and sonographic findings of hamartomas that were not classic on imaging, how pathologists distinguish the hamartoma from benign breast tissue on core samples, and reasons for discrepancies between core and surgical biopsy. Methods. A retrospective review of all image-recommended core biopsies between 1993 and 2001 was performed. There were 41 cases of hamartomas found on either core or surgical biopsy. The mammographic, sonographic, and pathologic findings were reviewed. Results. Of 41 hamartomas in 38 patients, 18 went on to surgical biopsy Of these 18 cases, 4 cases of hamartoma on core biopsy were fibroadenoma after excision; 2 cases of hamartoma on core biopsy were confirmed by surgery; and 12 cases of fibrocystic change after core biopsy were hamartoma after surgical biopsy. The 4 cases of fibroadenoma shown at final pathologic examination were excluded from imaging review, leaving 37 cases. In the 20 patients who underwent only core sampling, 23 hamartomas were diagnosed. Seventeen masses were visible on mammography, and 82% were homogeneously dense. of 36 masses shown on sonography, 86% were uniformly hypoechoic. At histologic examination, only 16% contained fat within the mass. Conclusions. Hamartomas may appear as homogeneously dense, well-circumscribed masses, varying in appearance from the classically described encapsulated mixed fatty-fibroglandular mass. Pathologists can make the diagnosis of hamartoma without the presence of adipose tissue but may have difficulty in distinguishing the hamartoma from fibrocystic change. However, if there is radiologic-pathologic concordance, further surgical excision is not warranted. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Georgian-Smith, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Wang Ambulatory Care Ctr 219Q,15 Parkman St, Boston, MA 02114 USA. EM dgeorgiansmith@partners.org NR 28 TC 15 Z9 18 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD OCT PY 2004 VL 23 IS 10 BP 1267 EP 1273 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 857TD UT WOS:000224140300002 PM 15448315 ER PT J AU Siroky, MB AF Siroky, MB TI Lower urinary tract symptoms: Shifting our focus from the prostate to the bladder SO JOURNAL OF UROLOGY LA English DT Editorial Material ID HYPERPLASIA C1 Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Siroky, MB (reprint author), Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. NR 5 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2004 VL 172 IS 4 BP 1237 EP 1238 DI 10.1097/01.ju.0000139987.77928.da PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 854JN UT WOS:000223899000002 PM 15371813 ER PT J AU Czito, B Zietman, A Kaufman, D Skowronski, U Shipley, W AF Czito, B Zietman, A Kaufman, D Skowronski, U Shipley, W TI Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter SO JOURNAL OF UROLOGY LA English DT Article DE ureter; carcinoma; transitional cell; kidney; radiotherapy; drug therapy ID UPPER URINARY-TRACT; PROGNOSTIC-FACTORS; RADIATION-THERAPY; CANCER; SURVIVAL AB Purpose: Transitional cell carcinoma of the upper urinary tract is a relatively uncommon malignancy. The role of adjuvant radiation therapy and chemotherapy is not well defined. We retrospectively reviewed the records of 31 patients who underwent surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy to determine overall outcome as well as impact of concurrent chemotherapy administration. Materials and Methods: Between 1970 and 1997, 31 patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (renal pelvis in 13, ureter in 15, and renal pelvis and ureter in 3) were treated with radiotherapy following attempted curative resection. Most patients (28 of 31) had T3/4 and/or N+ disease. The median radiation dose was 46.9 Gy. Nine patients received methotrexate, cisplatin and vinblastine chemotherapy for 2 to 4 cycles, followed by concurrent cisplatin with radiation. Results: Median followup was 2.6 years in all patients and 8.5 years in survivors. Median survival in all patients was 2.4 years. Of the patients 16 (52%) experienced disease relapse, including 9 (29%) with distant metastases alone. Seven patients (23%) experienced locoregional failure with distant metastases developing in all except 1 within 8 months of locoregional failure diagnosis. Five-year actuarial overall survival, disease specific survival, locoregional control and metastasis-free survival rates were 39%, 52%, 67% and 48%, respectively. On univariate analysis patients had improved 5-year actuarial overall and disease specific survival with the administration of concurrent chemotherapy (27% vs 67%, p = 0.01 and 41% vs 76%, p = 0.06, respectively). Conclusions: Our series suggests that the addition of concurrent cisplatin to adjuvant radiotherapy improves the ultimate outcome in patients with resected, locally advanced upper tract urothelial malignancies. This regimen should be considered in patients with T3/4 and/or node positive upper tract transitional cell carcinoma. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Czito, B (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA. EM czito001@mc.duke.edu NR 20 TC 48 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2004 VL 172 IS 4 BP 1271 EP 1275 DI 10.1097/01.ju.0000137910.38441.8a PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 854JN UT WOS:000223899000011 PM 15371822 ER PT J AU Andriole, G Bruchovsky, N Chung, LWK Matsumoto, AM Rittmaster, R Roehrborn, C Russell, D Tindall, D AF Andriole, G Bruchovsky, N Chung, LWK Matsumoto, AM Rittmaster, R Roehrborn, C Russell, D Tindall, D TI Dihydrotestosterone and the prostate: the scientific rationale for 5 alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia SO JOURNAL OF UROLOGY LA English DT Article DE prostate; dihydrotestosterone; prostatic hyperplasia; finasteride; GG 745 ID BONE-MINERAL DENSITY; FINASTERIDE; EXPRESSION; MEN; EPITHELIUM; TESTOSTERONE; DUTASTERIDE; STROMA; TYPE-1; CANCER AB Purpose: We reviewed the physiological and pathogenic role of dihydrotestosterone (DHT), evidence for the beneficial effects of decreasing DHT through 5alpha-reductase inhibition and the effects of altering the androgen balance with these agents. Materials and Methods: A review of the relevant literature was done using published studies identified from the MEDLINE database. Results: The androgens DHT and testosterone have complementary roles in male physiology. Each is mediated through the intracellular androgen receptor. It has been hypothesized that DHT may provide an amplification mechanism for testosterone, which could be a beneficial adaptation in men with low circulating testosterone. The recognition of the central role of DHT in benign prostatic hyperplasia (BPH) has changed the way the disease is viewed and has led to the introduction of 5alpha-reductase inhibitors, which can prevent and retard the progression of BPH by suppressing DHT synthesis. The 5alpha-reductase inhibitors decrease prostate volume. In doing so they improve symptoms and urinary flow, and decrease the risks of acute urinary retention and the need for BPH related surgery. The predominant drug related adverse events with 5a-reductase inhibitors are reproductive events, that is typically decreased libido, impotence and ejaculatory dysfunction. These events occur in a minority of men and tend to decrease with a longer treatment duration. Conclusions: DHT appears to have an obligatory role in the development of BPH. The role of 5alpha-reductase inhibitors in the treatment of BPH has been firmly established with an adverse events profile that is suitable for long-term use. C1 Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Washington, Sch Med & Geriatr Res Educ, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98195 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Mayo Clin, Coll Med, Rochester, MN USA. RP Andriole, G (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl,Campus Box 8242, St Louis, MO 63110 USA. OI Russell, David/0000-0002-0277-403X NR 20 TC 119 Z9 125 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2004 VL 172 IS 4 BP 1399 EP 1403 DI 10.1097/01.ju.0000139539.94828.29 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 854JN UT WOS:000223899000044 PM 15371854 ER PT J AU Greenberg, D Rosenfield, K Garcia, LA Berezin, RH Lavelle, T Fogleman, S Cohen, DJ AF Greenberg, D Rosenfield, K Garcia, LA Berezin, RH Lavelle, T Fogleman, S Cohen, DJ TI In-hospital costs of self-expanding nitinol stent implantation versus balloon angioplasty in the femoropopliteal artery (The VascuCoil trial) SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID REVASCULARIZATION PROCEDURES; DISEASE AB PURPOSE: Although several prospective studies have examined the safety and efficacy of stent placement for femoropopliteal arterial disease, the current cost of these procedures is unknown. To estimate and compare hospital costs associated with conventional balloon angioplasty (percutaneous transluminal angioplasty [PTAD and stent placement for patients with symptomatic peripheral arterial disease, the authors performed a prospective economic evaluation in conjunction with the Intracoil Femoropopliteal Stent Trial (VascuCoil). MATERIALS AND METHODS: Between May 1997 and December 1999, 266 patients with stenotic or occluded superficial femoral or popliteal arteries were prospectively randomized to treatment with the IntraCoil stent or PTA. Detailed resource use and cost data for each patient's initial revascularization procedure and ensuing hospitalization were collected and analyzed on an intention-to-treat basis. RESULTS: Compared with conventional balloon angioplasty, stent placement did not improve clinical outcomes but increased procedure duration, equipment costs, and physician services. As a result, initial hospital costs were approximately $3,500 higher for patients randomized to the IntraCoil stent, compared with PTA ($8,435 vs $4,980; P < .001). CONCLUSIONS: As performed in the VascuCoil trial, primary stent placement for femoropopliteal disease did not improve clinical outcomes but increased initial treatment costs by more than $3,000. Because there were no substantial differences in subsequent clinical outcomes between the two treatments, it is unlikely that these increased initial costs would be offset by savings in follow-up costs. These findings suggest that a strategy of routine stent implantation for patients undergoing femoropopliteal PTA is not optimal on economic grounds and that PTA with provisional stent implantation is preferred. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA. Harvard Clin Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. RP Cohen, DJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA. EM dcohen@bidmc.harvard.edu NR 16 TC 17 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2004 VL 15 IS 10 BP 1065 EP 1069 DI 10.1097/01.RVI.0000136293.18041.88 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XR UT WOS:000227678700006 PM 15466792 ER PT J AU Raffetto, JD Bernardo, J Menzoian, JO AF Raffetto, JD Bernardo, J Menzoian, JO TI Aortobifemoral graft infection with Mycobacterium tuberculosis: Treatment with abscess drainage, debridement, and long-term administration of antibiotic agents SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID AUTOGENOUS AORTOILIAC/FEMORAL RECONSTRUCTION; FEMORAL-POPLITEAL VEINS; GIANT-CELL ARTERITIS; MYCOTIC-ANEURYSM; ABDOMINAL-AORTA; EXPERIENCE; MANAGEMENT; FEASIBILITY; REPLACEMENT; DURABILITY AB Aortic graft infection with Mycobacterium tuberculosis is rare. We report a patient with a Dacron aortobifemoral prosthetic graft infection secondary to tuberculosis. The infection was successfully treated with surgical drainage without removal of the graft, and long-term antimycobacterial medications. A review of the literature contains only I other report of tuberculosis graft infection and treatment. We discuss a rare form of aortic graft infection from M tuberculosis and its treatment. C1 VA Boston Healthcare Syst, Dept Surg 112, Vasc Surg Sect, W Roxbury, MA 02132 USA. Boston Univ, Dept Surg, Med Ctr, Boston, MA 02215 USA. Boston Univ, Dept Med, Med Ctr, Boston, MA 02215 USA. RP Raffetto, JD (reprint author), VA Boston Healthcare Syst, Dept Surg 112, Vasc Surg Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov NR 20 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2004 VL 40 IS 4 BP 826 EP 829 DI 10.1016/j.jvs.2004.04.041 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 902WZ UT WOS:000227388700038 PM 15472616 ER PT J AU Gammack, JK Rudolph, JL Adedokun, A Hirth, V Kevorkian, R Misra, S AF Gammack, JK Rudolph, JL Adedokun, A Hirth, V Kevorkian, R Misra, S TI Perceptions of geriatric medicine junior faculty on success in academic medicine: The Saint Louis University Geriatric Academy (SLUGA) Faculty Development Program SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID PROFESSIONAL-DEVELOPMENT; MENTORING RELATIONSHIPS; CLINICAL-RESEARCH; SCHOOLS; EDUCATORS; SATISFACTION; PHYSICIANS; PROMOTION; TENURE C1 St Louis Univ, Div Geriatr Med, St Louis, MO 63104 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. Univ S Carolina, Sch Med, Div Geriatr, Columbia, SC 29208 USA. Vanderbilt Univ, Med Ctr, Tennessee Valley Hlth Care Syst Geriatr Res, Educ & Clin Ctr, Nashville, TN USA. RP Gammack, JK (reprint author), St Louis Univ, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA. EM gammackj@slu.edu NR 56 TC 1 Z9 1 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2004 VL 59 IS 10 BP 1029 EP 1035 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 868IQ UT WOS:000224907700007 PM 15528774 ER PT J AU Morgan, RO Virnig, BA Duque, M Abdel-Moty, E DeVito, CA AF Morgan, RO Virnig, BA Duque, M Abdel-Moty, E DeVito, CA TI Low-intensity exercise and reduction of the risk for falls among at-risk elders SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OLDER PERSONS; MOBILITY; STRENGTH; WOMEN; PROGRAM; PEOPLE; KNEE; GAIT; MEN AB Background. Among elderly persons, falls account for 87% of all fractures and are contributing factors in many nursing home admissions. This study evaluated the effect of an easily implemented, low-intensity exercise program on the incidence of falls and the time to first fall among a clinically defined population of elderly men and women. Methods. This community-based, randomized trial compared the exercise intervention with a no-intervention control. The participants were 294 men and women, aged 60 years or older, who had either a hospital admission or bed rest for 2 days or more within the previous month. Exercise participants were scheduled to attend exercise sessions lasting 45 minutes, including warm-up and cool-down, 3 times a week for 8 weeks (24 sessions). Assessments included gait and balance measures, self-reported physical function, the number of medications being taking at baseline, participant age, sex, and history of falling. Falls were tracked for 1 year after each participant's baseline assessment. Results. 29% of the study participants reported a fall during the study period. The effect of exercise in preventing falls varied significantly by baseline physical function level (p < .002). The risk for falls decreased for exercise participants with low baseline physical functioning (hazard ratio .5 1) but increased for exercise participants with high baseline physical functioning (hazard ratio, 3.51). Conclusions. This easily implemented, low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations, bed rest, or both who have low levels of physical functioning. C1 Houston VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Minneapolis, MN 55455 USA. Univ Miami, Sch Educ, Dept Exercise & Sport Sci, Coral Gables, FL 33124 USA. Miami VA Med Ctr, Hlth Serv Res & Dev Ctr, Miami, FL USA. Univ Miami, Coll Engn, Dept Ind Engn, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Dept Neurol Surg, Coral Gables, FL 33124 USA. Univ Miami, S Shore Hosp & Med Ctr, Comprehens Pain & Rehabil Ctr, Miami Beach, FL 33124 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Coral Gables, FL 33124 USA. RP Morgan, RO (reprint author), Houston VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM nnorgan@bcm.tmc.edu RI Morgan, Robert/A-8577-2009 NR 27 TC 41 Z9 43 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2004 VL 59 IS 10 BP 1062 EP 1067 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 868IQ UT WOS:000224907700012 PM 15528779 ER PT J AU Pritt, S Nostrant, JF Smith, B AF Pritt, S Nostrant, JF Smith, B TI PI can't go it alone SO LAB ANIMAL LA English DT Editorial Material C1 Harvard Univ, Sch Med, Ctr Anim Resources & Comparat Med, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Elm Hill Breeding Labs, Chelmsford, MA USA. Dana Farber Canc Inst, Anim Resources Facil, Boston, MA 02115 USA. RP Pritt, S (reprint author), Harvard Univ, Sch Med, Ctr Anim Resources & Comparat Med, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2004 VL 33 IS 9 BP 21 EP 22 DI 10.1038/laban1004-21b PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 860CI UT WOS:000224315500003 PM 15457195 ER PT J AU Burns, JA Kobler, JB Zeitels, SM AF Burns, JA Kobler, JB Zeitels, SM TI Microstereo-laryngoscopic lipoinjection: Practical considerations SO LARYNGOSCOPE LA English DT Article DE microlaryngoscopy; laryngoplasty; fat injection; lipoinjection; dysphonia; vocal cord; vocal fold; paralysis; dysphonia; glottic; glottis; hoarseness; laryngoscopy ID AUTOLOGOUS FAT INJECTION; VOCAL FOLD PARALYSIS; RECONSTRUCTION; PITFALLS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2004 VL 114 IS 10 BP 1864 EP 1867 DI 10.1097/00005537-200410000-00035 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 862CU UT WOS:000224468100035 PM 15454787 ER PT J AU Wiernik, PH Paietta, E Goloubeva, O Lee, SJ Makower, D Bennett, JM Wade, JL Ghosh, C Kaminer, LS Pizzolo, J Tallman, MS AF Wiernik, PH Paietta, E Goloubeva, O Lee, SJ Makower, D Bennett, JM Wade, JL Ghosh, C Kaminer, LS Pizzolo, J Tallman, MS CA ECOG TI Phase II study of theophylline in chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E4998) SO LEUKEMIA LA English DT Article DE B-cell CLL; theophylline; apoptosis ID HUMAN B-LYMPHOCYTES; DRUG-RESISTANCE; CD38 EXPRESSION; INDUCED APOPTOSIS; FLOW-CYTOMETRY; GENE MUTATION; CELL-DEATH; IN-VITRO; P53 GENE; CLL AB The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate ( cAMP). In 25 patients with Rai stages 0 - I, theophylline, 200 mg given orally every 12 h was well tolerated. There was one complete response after 22.5 months of treatment, which continues at 27+ months, and 18 other patients had stable disease. In vitro exposure of patients' lymphocytes to aminophylline ( 75 - 250 mug/ ml), the soluble form of theophylline, resulted in dose- and time-dependent induction of apoptosis in 9/20 patients studied. Apoptosis was documented flow-cytometrically by monitoring the expression of bcl-2 and bax, forward light scatter, fluorescence intensity of binding of CD45 antibody, and the binding of annexin. Patients whose leukemic lymphocytes were susceptible to apoptosis induction by aminophylline in vitro experienced a significantly longer progression-free survival than patients whose cells were resistant to the drug in culture ( P = 0.025). This suggests that in a CLL population treated with theophylline, induction of an apoptotic response to the drug in vitro is prognostic for absence of clinical progression. C1 New York Med Coll, Our Lady Mercy Hosp, Our Lady Mercy Canc Ctr, Ctr Comprehens Canc, Bronx, NY 10466 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. White Plains Hosp, White Plains, NY USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Decatur Mem Hosp, Decatur, GA USA. Iowa Blood & Canc Care, Cedar Rapids, IA USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Wiernik, PH (reprint author), New York Med Coll, Our Lady Mercy Hosp, Our Lady Mercy Canc Ctr, Ctr Comprehens Canc, 600 E 233rd St, Bronx, NY 10466 USA. EM PWiernik@aol.com NR 42 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2004 VL 18 IS 10 BP 1605 EP 1610 DI 10.1038/sj.leu.2403494 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 857NP UT WOS:000224124500010 PM 15356646 ER PT J AU An, J Sun, Y Fisher, M Rettig, MB AF An, J Sun, Y Fisher, M Rettig, MB TI Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas SO LEUKEMIA LA English DT Article DE proteasome inhibition; PS-341; primary effusion lymphoma; chemotherapy; TRAIL; NF-kappa B ID NF-KAPPA-B; PROTEASOME INHIBITOR PS-341; TRAIL-INDUCED APOPTOSIS; PROSTATE-CANCER CELLS; INTERFERON-ALPHA; ACTIVATION; RESISTANCE; AZIDOTHYMIDINE; MYELOMA; LIGAND AB Primary effusion lymphomas (PELs) are a rare type of non-Hodgkin's lymphoma that are resistant to cytotoxic chemotherapy. PELs manifest constitutive activation of nuclear factor kappa B (NF-kappaB), and inhibition of NF-kappaB induces apoptosis of PELs and sensitizes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced death. Bortezomib (PS-341), a peptidyl boronic acid inhibitor of the proteasome, is a potent agent against a wide range of hematologic malignancies and has been shown to inhibit NF-kappaB. Thus, we examined the cytotoxic effects of bortezomib alone and in combination with various drugs. Bortezomib potently inhibited NF-kappaB in PEL cells in a dose-dependent manner. In addition, bortezomib inhibited growth and induced apoptosis of PEL cell lines (IC50 values of 3.4 - 5.0 nM). Results of drug interactions between bortezomib and chemotherapy ( doxorubicin and Taxol) were schedule-dependent: synergistic interactions were generally observed when PEL cells were pretreated with bortezomib prior to chemotherapy, whereas additive or even antagonistic interactions occurred with chemotherapy pretreatment or simultaneous treatment with bortezomib and chemotherapy. Most schedules of bortezomib and dexamethasone were synergistic, although pretreatment with dexamethasone resulted in additive interactions. Effects of combinations of bortezomib and TRAIL were generally additive. Thus, bortezomib represents a promising potential therapy for the treatment of PEL. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), VAGLAHS W LA, 11301 Wilshire Blvd,Bldg 304,Room E1-113, Los Angeles, CA 90073 USA. EM matthew.rettig@med.va.gov FU NCI NIH HHS [5R01CA80004] NR 27 TC 61 Z9 64 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2004 VL 18 IS 10 BP 1699 EP 1704 DI 10.1038/sj.leu.2403460 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 857NP UT WOS:000224124500023 PM 15343345 ER PT J AU Tzachanis, D Lafuente, EM Li, LQ Boussiotis, VA AF Tzachanis, D Lafuente, EM Li, LQ Boussiotis, VA TI Intrinsic and extrinsic regulation of T lymphocyte quiescence SO LEUKEMIA & LYMPHOMA LA English DT Article DE T cell quiescence; autoimmunity; Foxp3; Tob; forkhead; regulatory T cell ID KRUPPEL-LIKE FACTOR; FORKHEAD TRANSCRIPTION FACTORS; NERVE GROWTH-FACTOR; CELL-CYCLE; FAMILY-MEMBER; TGF-BETA; C-MYC; CAENORHABDITIS-ELEGANS; TARGETED DISRUPTION; TOB/BTG1 FAMILY AB The outcome of an immune response is dependent on the interplay and complex interactions of positive (stimulatory) and negative (inhibitory) pathways and a major goal of modern immunology is to dissect these physiologic interactions in order to apply these physiologic mechanisms therapeutically. The balance of stimulatory and inhibitory signals is critical for maximizing the ability of the adoptive immune response to defend the host while maintaining immunologic tolerance and preventing autoimmunity. Cellular quiescence is a state characterized by decreased cell size and metabolic activity. The quiescent state of unstimulated T lymphocytes is thought to be due to the lack of activation signals. However, recent studies have shown that quiescence in lymphocytes is not a default state, but an actively maintained gene program. This program regulates intrinsic expression of quiescence factors in T lymphocytes. In addition to intrinsic mechanisms regulating T cell quiescence, CD4+CD25+ regulatory T cells (Treg) naturally arising in the thymus, engage in the maintenance of immunological self-tolerance by preventing autoimmunity in vivo in a non cell-autonomous manner. Although there is still only a rudimentary knowledge of the molecular mechanisms that govern the activity of the intrinsic quiescence factors and the development of Treg, it is now clear that immune quiescence is regulated by constitutively ongoing active mechanisms. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Room Mayer 547, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 FU NIAID NIH HHS [AI 43552, AI 46548] NR 75 TC 29 Z9 29 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2004 VL 45 IS 10 BP 1959 EP 1967 DI 10.1080/1042819042000219494 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 849FH UT WOS:000223523600001 PM 15370239 ER PT J AU Gertz, MA Rue, M Blood, E Kaminer, LS Vesole, DH Greipp, PR AF Gertz, MA Rue, M Blood, E Kaminer, LS Vesole, DH Greipp, PR TI Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): An eastern cooperative oncology group study (E3A98) SO LEUKEMIA & LYMPHOMA LA English DT Article DE lymphoplasmacytic lymphoma; monoclonal IgM protein; rituximab; Waldenstrom macroglobulinemia ID CONSENSUS PANEL RECOMMENDATIONS; ANTIBODY-MEDIATED IMMUNOTHERAPY; 2ND INTERNATIONAL WORKSHOP; FLUDARABINE THERAPY; CELL DISORDERS; PATIENT; REMISSION; INDUCTION; ANTIGENS AB Waldenstrom macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma that strongly expresses CD20 on the cell surface. This study was undertaken to determine the response rate of patients with untreated or previously treated WM to the monoclonal antibody rituximab, which is directed against CD20+ expressed by B-cell lymphomas. Thirty-four untreated and thirty-five previously treated patients received rituximab 375 mg/m(2) weekly for 4 consecutive weeks by intravenous infusion on days 1, 8, 15, and 22. Sixty-nine patients were evaluable for response; 19 (27.5%) achieved an objective response and 17 (24.6%) achieved a minor response. The overall response rate was 52.2% (90% CI [41.6%, 62.6%]). Of previously untreated patients 35.3% vs. 20% of previously treated patients achieved an objective response. Median response duration was not significantly different between previously untreated (27 months) and previously treated patients (not reached, P=0.8). Rituximab produced objective or minor responses in 52.2% of patients and is an active agent in the treatment of WM. Grade 4 toxicity was seen in 11%. C1 Mayo Clin, Div Hematol & Internal Med, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Gertz, MA (reprint author), Mayo Clin, Div Hematol & Internal Med, 200 1st St SW, Rochester, MN 55905 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA17145, CA13650, CA21115, CA23318, CA66636] NR 27 TC 91 Z9 94 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2004 VL 45 IS 10 BP 2047 EP 2055 DI 10.1080/10428190410001714043 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 849FH UT WOS:000223523600011 PM 15370249 ER PT J AU Olthoff, KM Brown, RS Delmonico, FL Freeman, RB McDiarmid, SV Merion, RM Millis, JM Roberts, JP Shaked, A Wiesner, RH Lucey, MR AF Olthoff, KM Brown, RS Delmonico, FL Freeman, RB McDiarmid, SV Merion, RM Millis, JM Roberts, JP Shaked, A Wiesner, RH Lucey, MR TI Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era SO LIVER TRANSPLANTATION LA English DT Article ID TRANSPLANTATION; MORTALITY AB A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document. C1 Univ Penn, Dept Surg, Div Transplantat, Philadelphia, PA 19104 USA. Columbia Presbyterian Med Ctr, Div Liver Dis & Transplant, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Div Transplantat, Dept Surg, Boston, MA 02111 USA. Univ Calif Los Angeles, Med Ctr, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90024 USA. Univ Michigan, Dept Surg, Hlth Syst, Ann Arbor, MI 48109 USA. Univ Chicago, Div Transplantat, Dept Surg, Chicago, IL 60637 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Mayo Clin & Mayo Fdn, William J von Liebig Transplant Ctr, Rochester, MN 55905 USA. Univ Wisconsin, Dept Med, Sect Gastroenterol & Hepatol, Madison, WI USA. RP Olthoff, KM (reprint author), Univ Penn, Dept Surg, Div Transplantat, 2 Dulles,3400 Spruce St, Philadelphia, PA 19104 USA. EM olthoff@uphs.upenn.edu NR 13 TC 96 Z9 100 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2004 VL 10 IS 10 SU 2 BP A6 EP A22 DI 10.1002/lt.2004.20247 PG 17 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 858EQ UT WOS:000224173600001 PM 15382225 ER PT J AU Johnson, BE AF Johnson, BE TI Extensive stage small cell lung cancer SO LUNG CANCER LA English DT Meeting Abstract CT 3rd International Chicago Symposium on Malignancies of the Chest and Head and Neck CY OCT 07-09, 2004 CL Chicago, IL C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD OCT PY 2004 VL 46 SU 1 BP S9 EP S9 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 859EE UT WOS:000224244700012 ER PT J AU Ma, PC Nallasura, V Uppalapati, R Nguyen, D Salgia, R AF Ma, PC Nallasura, V Uppalapati, R Nguyen, D Salgia, R TI C-Met/HGF biology and signal transduction in SCLC, especially as identified through a global proteomics phospho-antibody array based approach SO LUNG CANCER LA English DT Meeting Abstract CT 3rd International Chicago Symposium on Malignancies of the Chest and Head and Neck CY OCT 07-09, 2004 CL Chicago, IL C1 Univ Chicago, Pritzker Sch Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Nallasura, Vidya/D-8947-2011; Jagadeeswaran, Ramasamy/C-9987-2013 NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD OCT PY 2004 VL 46 SU 1 BP S49 EP S50 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 859EE UT WOS:000224244700060 ER PT J AU Masters, GA Xu, R Langer, CJ Dowlati, A Madajewicz, S Johnson, DH AF Masters, GA Xu, R Langer, CJ Dowlati, A Madajewicz, S Johnson, DH TI Updated results of a phase II study of carboplatin and gemcitabine with exisulind (IND # 65,056) in advanced non-small cell lung cancer (NSCLC) patients: eastern cooperative oncology group trial 1501 SO LUNG CANCER LA English DT Meeting Abstract CT 3rd International Chicago Symposium on Malignancies of the Chest and Head and Neck CY OCT 07-09, 2004 CL Chicago, IL C1 Helen Graham Canc Ctr, Newark, DE USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Hosp, Stony Brook, NY USA. Vanderbilt Univ, Nashville, TN USA. RI Johnson, David/A-7437-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD OCT PY 2004 VL 46 SU 1 BP S50 EP S51 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 859EE UT WOS:000224244700061 ER PT J AU Posner, MR Tishler, RB Norris, CM Wirth, L Haddad, RI AF Posner, MR Tishler, RB Norris, CM Wirth, L Haddad, RI TI The evolution of sequential therapy: combining induction chemotherapy; chemoradiotherapy, and surgery in the curative treatment of advanced head and neck cancer SO LUNG CANCER LA English DT Meeting Abstract CT 3rd International Chicago Symposium on Malignancies of the Chest and Head and Neck CY OCT 07-09, 2004 CL Chicago, IL C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD OCT PY 2004 VL 46 SU 1 BP S23 EP S24 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 859EE UT WOS:000224244700029 ER PT J AU Park, SW Hutchison, S Mehta, RH Isselbacher, EM Cooper, JV Fang, JM Evangelista, A Llovet, A Nienaber, CA Suzuki, T Pape, LA Eagle, KA Oh, JK AF Park, SW Hutchison, S Mehta, RH Isselbacher, EM Cooper, JV Fang, JM Evangelista, A Llovet, A Nienaber, CA Suzuki, T Pape, LA Eagle, KA Oh, JK TI Association of painless acute aortic dissection with increased mortality SO MAYO CLINIC PROCEEDINGS LA English DT Article ID MYOCARDIAL-INFARCTION; CLINICAL-FEATURES; PLEURAL EFFUSION; ASCENDING AORTA; DIAGNOSIS; ANEURYSM; MANAGEMENT; EPIDEMIOLOGY AB OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with painless acute aortic dissection (AAD). PATIENTS AND METHODS: For this study conducted from 3.997 to 2001, we searched the International Registry of Acute Aortic Dissection to identify patients with painless AAD (group 1). Their clinical features and in-hospital events were compared with patients who had painful AAD (group 2). RESULTS: Of the 977 patients in the database, 63 (6.4%) had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older than those in group 2 (mean +/- SD age, 66.6+/-13.3 vs 61.9+/-14.1 years; P=.01). Type A dissection (involving the ascending aorta or the arch) was more frequent in group 1 (74.6% vs 60.9%; P=.03). Syncope (33.9% vs 11.7%; P<.001), congestive heart failure (19.7% vs 3.9%; P<.001), and stroke (11.3% vs 4.7%; P=.03) were more frequent presenting signs in group 1. Diabetes (10.2% vs 4.0%; P=.04), aortic aneurysm (29.5% vs 13.1%; P<.001), and prior cardiovascular surgery (48.1% vs 19.7%; P<.001) were also more common in group 1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P=.05), especially due to type B dissection (limited to the descending aorta) (43.8% vs 10.4%; P<.001), and the prevalence of aortic rupture was higher among patients with type B dissection in group 1 (11.8.8% vs 5.9%; P=.04). CONCLUSION: Patients with painless AAD had syncope, congestive heart failure, or stroke. Compared with patients who have painful AAD, patients who have painless AAD have higher mortality, especially when AAD is type B. C1 Mayo Clin, Coll Med, Div Cardiovasc Dis & Internal Med, Rochester, MN 55905 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Barcelona, Hosp Gen Valle Hebron, Barcelona, Spain. Univ Madrid, Hosp 12 Octubre, Madrid 3, Spain. Univ Rostock, Rostock, Germany. Univ Tokyo, Tokyo, Japan. Univ Massachusetts Hosp, Worcester, MA USA. RP Oh, JK (reprint author), Mayo Clin, Coll Med, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. EM oh.jae@mayo.edu NR 25 TC 56 Z9 61 U1 1 U2 9 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2004 VL 79 IS 10 BP 1252 EP 1257 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 858MS UT WOS:000224196500005 PM 15473405 ER PT J AU Echchgadda, I Song, CS Oh, TS Cho, SH Rivera, OJ Chatterjee, B AF Echchgadda, I Song, CS Oh, TS Cho, SH Rivera, OJ Chatterjee, B TI Gene regulation for the senescence marker protein DHEA-sulfotransferase by the xenobiotic-activated nuclear pregnane X receptor (PXR) SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; Sult2A1; xenobiotic metabolism; nuclear receptors; PXR; sulfonation ID CONSTITUTIVE ANDROSTANE RECEPTOR; HUMAN CYTOSOLIC SULFOTRANSFERASES; RAT-LIVER; DEHYDROEPIANDROSTERONE-SULFOTRANSFERASE; MOLECULAR-CLONING; HYDROXYSTEROID SULFOTRANSFERASE; ANDROGEN RECEPTOR; LITHOCHOLIC ACID; MESSENGER-RNA; BILE-ACIDS AB Dehydroepiandrosterone (DHEA)-sulfotransferase (SULT2A1) is a phase 11 metabolizing/detoxifying enzyme with substrate preference for physiological hydroxysteroids, diverse drugs and other xenobiotics. The first-pass,tissues (liver and intestine) express SULT2A1 at high levels. In senescent male rodents, Sult2A1 gene transcription in the liver is markedly enhanced and calorie restriction retards this increase. Age-associated loss of the liver expression of androgen receptor in part explains the up-regulation of Sult2A1 expression at late life, since androgen receptor is a negative regulator of this gene. In line with its role in xenobiotic metabolism, the Sidt2A1 gene is induced by the pregnane X receptor (PXR). PXR is a xenosensing nuclear receptor that is activated by endobiotic (natural steroids) and xenobiotic (therapeutic drugs and environmental chemicals) molecules. An inverted-repeat arrangement (IR0) of the consensus half site binding sequence for nuclear receptors mediates the xenobiotic induction of the Sult2A1 promoter. The IR0 element is a specific binding site for PXR and its heterodimer partner retinoid X receptor (RXR-alpha) and it directs PXR-mediated induction of a heterologous promoter. In contrast to the loss of androgen receptor expression, PXR and RXR-alpha mRNA expression is invariant during aging. Repression by the androgen receptor and induction by PXR may act coordinately to cause the senescence associated and xenobiotic mediated stimulation of Sult2A1 transcription. Increased Sult2A1 expression appears to be an adaptive response to ensure optimal metabolism of Sult2A1 substrates at old age. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM chatterjee@uthscsa.edu FU NIA NIH HHS [T32 AG 00165, R01 AG 10486] NR 81 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT-NOV PY 2004 VL 125 IS 10-11 BP 733 EP 745 DI 10.1016/j.mad.2004.08.008 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 877ZM UT WOS:000225614800009 PM 15541768 ER PT J AU Vijg, J AF Vijg, J TI Impact of genome instability on transcription regulation of aging and senescence SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE genome instability; somatic mutations; gene regulation; aging ID TRANSGENIC MOUSE MODEL; IN-VIVO MUTATIONS; SOMATIC MUTATION; GENE-EXPRESSION; AGE; MICE; ACCUMULATION; CHROMOSOME; REARRANGEMENTS; RESTRICTION AB Genomic instability has been implicated as a major stochastic mechanism of aging. Using a transgenic mouse model with chromosomally integrated lacZ mutational target genes, mutations were found to accumulate with age at an organ- and tissue-specific rate. Also, the spectrum of age-accumulated mutations was found to differ greatly from organ-to-organ; while initially similar, mutation spectra of different tissues diverged significantly over the lifetime. To explain how genomic instability, which is inherently stochastic, can be a causal factor in aging, it is proposed that randomly induced mutations may adversely affect normal patterns of gene regulation, resulting in a mosaic of cells at various stages on a trajectory of functional decline, eventually resulting in cell death or neoplastic transformation. To directly address this question, we demonstrate that it is now possible to analyze single cells, isolated from old and young tissues, for specific alterations in gene expression. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, STCBM Bldg,Suite 2-200,15355 Lambda, San Antonio, TX 78245 USA. EM vijg@uthsesa.edu FU NIA NIH HHS [AG 17242] NR 39 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT-NOV PY 2004 VL 125 IS 10-11 BP 747 EP 753 DI 10.1016/j.mad.2004.07.004 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 877ZM UT WOS:000225614800010 PM 15541769 ER PT J AU Clark, RA Valente, AJ AF Clark, RA Valente, AJ TI Nuclear factor kappa B activation by NADPH oxidases SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE ageing; NADPH oxidase; NF-kappa B; NOX; superoxide ID CHRONIC GRANULOMATOUS-DISEASE; TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE-CELLS; HEMATOLOGICALLY IMPORTANT MUTATIONS; SIGNAL-TRANSDUCTION PATHWAYS; PEROXIDE-HALIDE SYSTEM; HUMAN-NEUTROPHILS; TRANSCRIPTION FACTOR; REACTIVE OXYGEN; HYDROGEN-PEROXIDE AB Reactive oxygen species (ROS) initiate activation of the transcription factor NF-kappaB in a variety of cell systems. Perhaps the most potent biological source of ROS is the NADPH oxidase of phagocytic cells, a multi-component system that catalyzes the formation of superoxide anion. Although phagocytes use this oxidase to kill ingested microorganisms, the products also mediate a broad range of biological oxidation reactions and some evidence exists for activation of NF-kappaB through this mechanism. Moreover, the components of the phagocyte NADPH oxidase are present in certain non-phagocytic cells and recently discovered homologues of the catalytic component gp91(phox) are expressed in a number of tissues. We explored the hypothesis that the products of NADPH oxidases cause the activation of NF-kappaB. K562 human erythrokeukemia cells transfected with constructs for expression of gp91(phox), plus other essential NADPH oxidase components generated substantial amounts of superoxide when activated with phorbol ester, lesser amounts with arachidonic acid exposure, and none with TNFalpha. Gel shift assays demonstrated induction of NF-KB in K562 cells exposed to TNFa and specificity was shown by oligonucleotide competition. Supershift assays demonstrated the presence in nuclear complexes of the NF-kappaB components p65/RelA and p50. Nuclear complexes of identical electrophoretic mobility were induced in phorbol ester-stimulated K562 cells that expressed the complete NADPH oxidase system, but not in cells lacking one of the essential oxidase components. K562 cells were relatively resistant to NF-KB induction by exogenous peroxide, but certain other cell types (HEK293 and HeLaS3) demonstrated such induction upon exposure to reagent hydrogen peroxide or glucose oxidase plus glucose and this was blocked by catalase. Finally, we found a biphasic pattern of gp91(phox) expression in rat liver during aging. High levels observed in young animals decreased in middle age, but increased again in old age. Collectively, these studies demonstrate the potential for NADPH-dependent induction of NF-KB and raise the possibility of a role for this pathway in the biology of aging. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM clarkra@uthscsa.edu FU NIA NIH HHS [R01 AG019519, R01 AG 19519] NR 82 TC 40 Z9 41 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT-NOV PY 2004 VL 125 IS 10-11 BP 799 EP 810 DI 10.1016/j.mad.2004.08.009 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 877ZM UT WOS:000225614800015 PM 15541774 ER PT J AU Bokov, A Chaudhuri, A Richardson, A AF Bokov, A Chaudhuri, A Richardson, A TI The role of oxidative damage and stress in aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE antioxidants; oxidative damage; oxidative stress; free radicals ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; METHIONINE SULFOXIDE REDUCTASE; EXTENDED LIFE-SPAN; ADULT DROSOPHILA-MELANOGASTER; METAL-CATALYZED OXIDATION; TERM CALORIC RESTRICTION; FREE-RADICAL THEORY; LONG-LIVED STRAIN; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION AB The Free Radical/Oxidative Stress Theory of Aging, which was first proposed in 1956, is currently one of the most popular explanations for how aging occurs at the biochemical/molecular level. However, most of the evidence in support of this theory is correlative, e.g., oxidative damage to various biomolecules increases with age, and caloric restriction, which increases life span and retards aging, reduces the age-related increase in oxidative damage to biomolecules. The most direct test of the Free Radical/Oxidative Stress Theory of Aging is to specifically alter the age-related increase in oxidative damage and determine how this alteration affects life span. For the first time, investigators can use genetically altered animals to test directly the role of oxidative damage in aging. In this manuscript, we critically review the past research in this area and discuss potential future research directions in testing the Free Radical/Oxidative Theory of Aging. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu NR 194 TC 317 Z9 333 U1 2 U2 29 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT-NOV PY 2004 VL 125 IS 10-11 BP 811 EP 826 DI 10.1016/j.mad.2004.07.009 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 877ZM UT WOS:000225614800016 PM 15541775 ER PT J AU Chren, MM Sahay, AP Sands, LP Maddock, L Lindquist, K Bertenthal, D Bacchetti, P AF Chren, MM Sahay, AP Sands, LP Maddock, L Lindquist, K Bertenthal, D Bacchetti, P TI Variation in care for nonmelanoma skin cancer in a private practice and a veterans affairs clinic SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 15-18, 2002 CL LOS ANGELES, CA SP Soc Investigat Dermatol DE practice variation; ambulatory care; skin cancer ID BASAL-CELL CARCINOMA; PATIENT; SURGERY AB Background: Nonmelanoma skin cancer is the most common malignancy. Multiple therapies prevent recurrence but vary widely in cost. The most common therapies are local destruction, excision, and Mohs surgery (histologically guided tumor removal). Clinical variables that may affect treatment choices can be identified, but little is known about how clinicians choose among therapies. Objective: The objective of this study was to learn if variations exist in the treatment of nonmelanoma skin cancer in different practice settings. Research Design: Prospective cohort study. Subjects: Subjects consisted of consecutive patients with nonmelanoma skin cancer at a university-affiliated private dermatology practice and the dermatology clinic at the nearby affiliated Veterans Affairs (VA) medical center. Data: We studied data from medical records and patient surveys. Results: Overall, 1777 nonrecurrent nonmelanoma skin cancers were diagnosed in 1375 patients. Compared with the VA site, patients at the private site were younger, more likely to be female, and less likely to be poor, and their tumors were smaller and less likely to be on visible areas of the body. Treatments varied between the 2 sites (P < 0.001). The proportions of tumors treated at the private and VA sites, respectively, were 23% and 19% for destruction, 25% and 48% for excision, and 37% and 25% for Mohs surgery. In multiple clinical subgroups, Mohs surgery was more likely to be performed at the private site than at the VA. Moreover, in multivariable models controlling for clinical features that may have affected treatment choice, tumors at the private site were more likely than tumors at the VA to be treated with Mohs surgery (odds ratio, 2.39; 95% confidence interval, 1.54-3.70). Conclusions: Care for nonmelanoma skin cancer varied at 2 academic practice sites that are near each other and that share some clinician staff. These findings raise questions not only about overuse or underuse of procedures at the 2 sites, but also about systematic differences in patient preferences and/or physician incentives in prepaid and fee-for-service settings. C1 San Francisco VAMC, Dermatol Serv, San Francisco, CA 94121 USA. San Francisco VAMC, Dept Vet Affairs, Interdisciplinary Res Program Improve Care Older, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Chren, MM (reprint author), San Francisco VAMC, Dermatol Serv, 151R,4150 Clement St, San Francisco, CA 94121 USA. EM mmchren@itsa.ucsf.edu RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU NIAMS NIH HHS [K02 AR 02203-01] NR 16 TC 20 Z9 20 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 2004 VL 42 IS 10 BP 1019 EP 1026 DI 10.1097/00005650-200410000-00011 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 858MW UT WOS:000224196900011 PM 15377935 ER PT J AU Pietz, K Ashton, CM McDonell, M Wray, NP AF Pietz, K Ashton, CM McDonell, M Wray, NP TI Predicting healthcare costs in a population of veterans affairs beneficiaries using diagnosis-based risk adjustment and self-reported health status SO MEDICAL CARE LA English DT Article DE risk adjustment; case-mix; health status ID CASE-MIX MEASURES; CAPITATION RATES; CHRONIC DISEASE; INFORMATION; HOSPITALS; OUTCOMES; MODEL AB Background: Many healthcare organizations use diagnosis-based risk adjustment systems for predicting costs. Health self-report may add information not contained in a diagnosis-based system but is subject to incomplete response. Objective: The objective of this study was to evaluate the added predictive power of health self-report in combination with a diagnosis-based risk adjustment system in concurrent and prospective models of healthcare cost. Research Design: This was a cohort study using Department of Veterans Affairs (VA) administrative databases. We tested the predictive ability of the Adjusted Clinical Group (ACG) methodology and the added value of SF-36V (short form functional status for veterans) results. Linear regression models were compared using R-2, mean absolute prediction error (MAPE), and predictive ratio. Subjects: Subjects were 35,337 VA beneficiaries at 8 VA medical centers during fiscal year (FY) 1998 who voluntarily completed an SF-36V survey. Measures: Outcomes were total FY 1998 and FY 1999 cost. Demographics and ACG-based Adjusted Diagnostic Groups (ADGs) with and without 8 SF-36V multiitem scales and the Physical Component Score and Mental Component Score were compared. Results: The survey response rate was 45%. Adding the 8 scales to ADGs and demographics increased the crossvalidated R-2 by 0.007 in the prospective model. The 8 scales reduced the MAPE by $236 among patients in the upper 10% of FY 1999 cost. Conclusions: The limited added predictive power of health self-report to a diagnosis-based risk adjustment system should be weighed against the cost of collecting these data. Adding health self-report data may increase predictive accuracy in high-cost patients. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NW Healthcare Serv Res & Dev Ctr Excellence, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Dept Vet Affairs, Washington, DC USA. RP Pietz, K (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM kpietz@bcm.tmc.edu NR 27 TC 29 Z9 29 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 2004 VL 42 IS 10 BP 1027 EP 1035 DI 10.1097/00005650-200410000-00012 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 858MW UT WOS:000224196900012 PM 15377936 ER PT J AU Jiang, H Paganetti, H AF Jiang, H Paganetti, H TI Adaptation of GEANT4 to Monte Carlo dose calculations based on CT data SO MEDICAL PHYSICS LA English DT Article DE GEANT4; Monte Carlo; CT ID MULTIPLE SOURCE MODEL; BEAM; SIMULATION; RADIOTHERAPY; ALGORITHM; TOOLKIT AB The GEANT4 Monte Carlo code provides many powerful functions for conducting particle transport simulations with great reliability and flexibility. However, as a general purpose Monte Carlo code, not all the functions were specifically designed and fully optimized for applications in radiation therapy. One of the primary issues is the computational efficiency, which is especially critical when patient CT data have to be imported into the simulation model. In this paper we summarize the relevant aspects of the GEANT4 tracking and geometry algorithms and introduce our work on using the code to conduct dose calculations based on CT data. The emphasis is focused on modifications of the GEANT4 source code to meet the requirements for fast dose calculations. The major features include a quick voxel search algorithm, fast volume optimization, and the dynamic assignment of material density. These features are ready to be used for tracking the primary types of particles employed in radiation therapy such as photons, electrons, and heavy charged particles. Recalculation of a proton therapy treatment plan generated by a commercial treatment planning program for a paranasal sinus case is presented as an example. (C) 2004 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jiang, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NCI NIH HHS [CA 21239] NR 21 TC 69 Z9 71 U1 1 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2004 VL 31 IS 10 BP 2811 EP 2818 DI 10.1118/1.1796952 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 865ZR UT WOS:000224743200013 PM 15543788 ER PT J AU Klein, RL McHenry, MB Lok, KH Hunter, SJ Le, NA Jenkins, AJ Zheng, D Semler, AJ Brown, WV Lyons, TJ Garvey, WT AF Klein, RL McHenry, MB Lok, KH Hunter, SJ Le, NA Jenkins, AJ Zheng, D Semler, AJ Brown, WV Lyons, TJ Garvey, WT CA DCCTEDIC Res Grp TI Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes: Associations with lipoprotein subclasses SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CORONARY-ARTERY-DISEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; FAMILIAL COMBINED HYPERLIPIDEMIA; TRIGLYCERIDE-RICH LIPOPROTEINS; FRAGMENT-LENGTH-POLYMORPHISMS; INSULIN-RESPONSE ELEMENT; HEART-DISEASE; APOC-III; A-I; PLASMA-LIPOPROTEINS AB Serum apolipoprotein C-III (apoCIII) concentration and apoCIII gene polymorphisms have been shown to be a risk factor for cardiovascular disease; however, the underlying mechanisms remain unclear. In addition, no studies have been performed that address these issues in type 1 diabetes. The current study investigated apoCIII protein and apoCIII gene variation in a normotriglyceridemic (82 +/- 57 mg/dL) population of patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort. Blood samples were obtained in 409 patients after an overnight fast. Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile. Higher apoCIII concentrations were associated (P < .0001) with increased triglycerides (r = 0.78), total (r = 0.61) and low-density lipoprotein (LDL) (r = 0.40) cholesterol, apoA-I (r = 0.26), and apoB (r = 0.50), and these relationships persisted after controlling for age, gender, body mass index (BMI), and hemoglobin A(1c) (HbA(1c)). Nuclear magnetic resonance (NMR) lipoprotein subclass analyses demonstrated that apoCIII was correlated with an increase in very-low-density lipoprotein (VLDL) subclasses (P = .0001). There also was a highly significant positive relationship between serum apoCIII concentration and the LDL particle concentration in both men (r = 0.49, P = .001) and women (r = 0.40, P = .001), and a highly significant negative relationship between serum apoCIII levels and average LDL particle size in both men (r = -0.37, P = .001) and women (r = -0.22, P = .001) due primarily to an augmentation in the small L1 subclass (r = 0.42, P = .0001). Neither the T-455-->C polymorphism affecting an insulin response element in the apoCIII gene promoter nor a Sad polymorphism in the 3'UTR were associated with any alterations in circulating apoCIII concentrations, serum lipids, apolipoprotein concentrations, lipoprotein composition, or parameters measured by NMR lipoprotein subclass analyses. In summary, elevated apoCIII concentration was associated with risk factors for cardiovascular disease in normolipidemic type 1 diabetic patients through associated changes in lipoprotein subfraction distributions, which were independent of apoCIII genotype. (C) 2004 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Res Serv, Ralph H Johnson Dept, Charleston, SC 29403 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Emory Univ, Div Atherosclerosis & Lipid Metab, Atlanta, GA 30322 USA. Univ Melbourne, St Vincent Hosp, Dept Med, Fitzroy, Vic 3052, Australia. Univ Oklahoma, Hlth Sci Fdn, Sect Endocrinol Diabet & Hypertens, Oklahoma City, OK USA. Vet Affairs Med Ctr, Birmingham, AL USA. DCCT, NDIC, Bethesda, MD USA. RP Klein, RL (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, 114 Doughty St,POB 250770, Charleston, SC 29425 USA. RI Jenkins, Alicia/N-2482-2015; Hegele, Robert/G-3301-2011; OI Le, Ngoc-Anh/0000-0002-2634-4798 FU NHLBI NIH HHS [P01-HL55782] NR 57 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2004 VL 53 IS 10 BP 1296 EP 1304 DI 10.1016/j.metabol.2004.05.004 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 861MT UT WOS:000224421500008 PM 15375785 ER PT J AU Busch, A Marasco, WA Doebis, C Volk, HD Seifert, M AF Busch, A Marasco, WA Doebis, C Volk, HD Seifert, M TI MHC class I manipulation on cell surfaces by gene transfer of anti-MHC class I intrabodies - a tool for decreased immunogenicity of allogeneic tissue and cell transplants SO METHODS LA English DT Article DE intrabodies; antibodies intracellular; major histocompatibility antigen class I; tissue engineering; transfection; fusionprotein; bicistronic expression ID HUMAN EPIDERMAL KERATINOCYTES; TIME-RESOLVED FLUORESCENCE; LABELED TARGET-CELLS; INTRACELLULAR ANTIBODIES; MUTANT MICE; THERAPEUTIC MOLECULES; ENDOPLASMIC-RETICULUM; SKIN EQUIVALENT; LANGERHANS CELL; DEFICIENT MICE AB Intrabodies (IB) are suitable tools to down-regulate the expression of cell surface molecules in general. In this work, the appearance of major histocompatibility (MHC) class I molecules on the cell surface could be prevented by the expression of intracellularly localized anti-MHC class I antibodies. The expression of MHC antigens presenting intracellularly synthetised peptides on the cell surface is the predominant reason for immunologic detection and rejection of allogeneic cell and tissue transplants. Allogeneic keratinocyte sheets might be a suitable tool for skin grafting. Within this study primary rat keratinocytes have been transfected with anti-MHC I-IB. Strong IB-expressing cells showed a MHC I "knockout" phenotype. The cells did not exhibit any significant alterations compared to non-transfected cells: the cell growth and the expression of other surface molecules were unaltered. Merely an enhanced intracellular accumulation of MHC I molecules could be detected. Notably, IB-expressing keratinocytes displayed a reduced susceptibility to allogeneic cytotoxic T cells in vitro compared to unmodified cells with a normal level of MHC I surface expression. These MHC I-deficient keratinocytes might be utilized in tissue-engineered allogeneic non-immunogeneic skin transplants. The principle of MHC class I manipulation in general can be used for other allogeneic cell and tissue-engineered transplants as well. (C) 2004 Elsevier Inc. All rights reserved. C1 Humboldt Univ, Sch Med, Dept Med Immunol, D-10098 Berlin, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Seifert, M (reprint author), Humboldt Univ, Sch Med, Dept Med Immunol, Schumannstr 20-21, D-10098 Berlin, Germany. EM martina.seifert@charite.de NR 54 TC 11 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD OCT PY 2004 VL 34 IS 2 BP 240 EP 249 DI 10.1016/j.ymeth.2004.03.017 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 860VC UT WOS:000224370700010 PM 15312677 ER PT J AU Cohen, SP Larkin, TM AF Cohen, SP Larkin, TM TI The causes of false-positive medial branch (Facet joint) blocks in soldiers and retirees SO MILITARY MEDICINE LA English DT Article ID LOW-BACK-PAIN; ZYGAPOPHYSIAL JOINTS; CLINICAL-FEATURES; LUMBAR; DISCOGRAPHY; DENERVATION; DISC; SPECIFICITY; PREVALENCE; NEUROTOMY AB Objective: The purpose of this study was to determine the factors associated with false-positive medial branch blocks (MBB), the nerve blocks used to diagnose facet arthropathy, in soldiers and retirees. Methods: The study subjects were 78 patients with chronic low back pain who underwent diagnostic MBB to determine whether or not the facet joints were pain generators. Radiofrequency denervation of these nerves was performed in all patients with positive responses. Patients who failed to obtain pain relief after the blocks (negative blocks) and those who obtained temporary pain relief after MBB but failed radiofrequency denervation (false-positive blocks) then proceeded to undergo discography. Based on patients' responses to diagnostic blocks, discography results, the presence of radicular pain, and previous back surgery, the data were analyzed to determine whether any of these variables correlated with false-positive MBB. Results: The presence of discogenic or radicular pain was not associated with a higher false-positive response rate to MBB. Conversely, the absence of discogenic pain was associated with a higher percentage of false-positive blocks. There was also a trend for patients with previous back surgery to have a higher false-positive rate than those who had not undergone previous surgery. Conclusions: Although a high incidence of epidural and foraminal spread occurs during the performance of MBB, this is unlikely to be a significant cause of false-positive blocks. C1 Walter Reed Army Med Ctr, Dept Anesthesiol, Pain Management Ctr, Dept Anesthesiol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Pain Ctr,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Cohen, SP (reprint author), Walter Reed Army Med Ctr, Dept Anesthesiol, Pain Management Ctr, Dept Anesthesiol, Washington, DC 20307 USA. NR 32 TC 11 Z9 11 U1 0 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2004 VL 169 IS 10 BP 781 EP 786 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 019JC UT WOS:000235830400006 PM 15532341 ER PT J AU Oliva, E Gonzalez, L Dionigi, A Young, RH AF Oliva, E Gonzalez, L Dionigi, A Young, RH TI Mixed tumors of the vagina: an immunohistochemical study of 13 cases with emphasis on the cell of origin and potential aid in differential diagnosis SO MODERN PATHOLOGY LA English DT Article DE vagina; mixed tumors; immunohistochemistry; histogenesis ID EPITHELIAL MEMBRANE ANTIGEN; ENDOMETRIAL STROMAL TUMORS; PLEOMORPHIC ADENOMA; SYNOVIAL SARCOMA; ENDOCERVICAL STROMA; CD10 EXPRESSION; HUMAN-TISSUES; NEOPLASMS; IMMUNOREACTIVITY; MYOEPITHELIOMAS AB Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 53 TC 17 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2004 VL 17 IS 10 BP 1243 EP 1250 DI 10.1038/modpathol.3800173 PG 8 WC Pathology SC Pathology GA 857CU UT WOS:000224094600009 PM 15154010 ER PT J AU Du, XB Shen, J Kugan, N Furth, EE Lombard, DB Cheung, C Pak, S Luo, GB Pignolo, RJ DePinho, RA Guarente, L Johnson, FB AF Du, XB Shen, J Kugan, N Furth, EE Lombard, DB Cheung, C Pak, S Luo, GB Pignolo, RJ DePinho, RA Guarente, L Johnson, FB TI Telomere shortening exposes functions for the mouse Werner and bloom syndrome genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELLS LACKING TELOMERASE; SACCHAROMYCES-CEREVISIAE; RECQ HELICASES; IN-VITRO; SYNDROME FIBROBLASTS; GENOME MAINTENANCE; SYNDROME PROTEIN; TUMOR-FORMATION; AGING PROCESS; DNA HELICASE AB The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. MIT, Dept Biol, Cambridge, MA USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. RP Johnson, FB (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 405A Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. EM johnsonb@mail.med.upenn.edu NR 61 TC 142 Z9 147 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2004 VL 24 IS 19 BP 8437 EP 8446 DI 10.1128/MCB.24.19.8437-8446.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 855QZ UT WOS:000223990100012 PM 15367665 ER PT J AU Litovchick, L Chestukhin, A DeCaprio, JA AF Litovchick, L Chestukhin, A DeCaprio, JA TI Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; RETINOBLASTOMA GENE FAMILY; RB-RELATED P107; CELL-CYCLE; PROTEIN P130; MICE LACKING; DEPENDENT PHOSPHORYLATION; SUBSTRATE-SPECIFICITY; TARGETED DISRUPTION; G(1) CONTROL AB Phosphorylation of the retinoblastoma-related or pocket proteins RB1/pRb, RBL1/p107, and RBL2/p130 regulates cell cycle progression and exit. While all pocket proteins are phosphorylated by cyclin-dependent kinases (CDKs) during the G(1)/S-phase transition, p130 is also specifically phosphorylated in G(0)-arrested cells. We have previously identified several phosphorylated residues that match the consensus site for glycogen synthase kinase 3 (GSK3) in the G(0) form of p130. Using small-molecule inhibitors of GSK3, site-specific mutants of p130, and phospho-specific antibodies, we demonstrate here that GSK3 phosphorylates p130 during G(0). Phosphorylation of p130 by GSK3 contributes to the stability of p130 but does not affect its ability to interact with E2F4 or cyclins. Regulation of p130 by GSK3 provides a novel link between growth factor signaling and regulation of the cell cycle progression and exit. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Mayer 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01-CA63113, R01 CA063113] NR 61 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2004 VL 24 IS 20 BP 8970 EP 8980 DI 10.1128/MCB.24.20.8970-8980.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 859CG UT WOS:000224239100016 PM 15456871 ER PT J AU Chen, TP Tsujimoto, N Li, E AF Chen, TP Tsujimoto, N Li, E TI The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; ICF SYNDROME; METHYLTRANSFERASE GENE; CYTOSINE-5 METHYLTRANSFERASES; IMMUNODEFICIENCY SYNDROME; MAINTENANCE METHYLATION; MAMMALIAN DEVELOPMENT; FAMILY; EXPRESSION AB Dnmt3a and Dnmt3b are responsible for the establishment of DNA methylation patterns during development. These proteins contain, in addition to a C-terminal catalytic domain, a unique N-terminal regulatory region that harbors conserved domains, including a PWWP domain. The PWWP domain, characterized by the presence of a highly conserved proline-tryptophan-tryptophan-proline motif, is a module of 100 to 150 amino acids found in many chromatin-associated proteins. However, the function of the PWWP domain remains largely unknown. In this study, we provide evidence that the PWWP domains of Dnmt3a and Dnmt3b are involved in functional specialization of these enzymes. We show that both endogenous and green fluorescent protein-tagged Dnmt3a and Dnmt3b are particularly concentrated in pericentric heterochromatin. Mutagenesis analysis indicates that their PWWP domains are required for their association with pericentric heterochromatin. Disruption of the PWWP domain abolishes the ability of Dnmt3a and Dnmt3b to methylate the major satellite repeats at pericentric heterochromatin. Furthermore, we demonstrate that the Dnmt3a PWWP domain has little DNA-binding ability, in contrast to the Dnmt3b PWWP domain, which binds DNA nonspecifically. Collectively, our results suggest that the PWWP domains of Dnmt3a and Dnmt3b are essential for targeting these enzymes to pericentric heterochromatin, probably via a mechanism other than protein-DNA interactions. C1 Novartis Inst Biomed Res, Epigenet Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Li, E (reprint author), Novartis Inst Biomed Res, Epigenet Program, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM en.li@pharma.novartis.com FU NCI NIH HHS [CA82389, R01 CA082389]; NIGMS NIH HHS [GM52106] NR 41 TC 108 Z9 120 U1 3 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2004 VL 24 IS 20 BP 9048 EP 9058 DI 10.1128/MCB.24.20.9048-9058.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 859CG UT WOS:000224239100023 PM 15456878 ER PT J AU Farina, A Hattori, M Qin, J Nakatani, Y Minato, N Ozato, K AF Farina, A Hattori, M Qin, J Nakatani, Y Minato, N Ozato, K TI Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its activity and subcellular localization SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EFFECT HOMEOTIC GENE; FAMILY PROTEINS; LIVING CELLS; RAP1; RAS; CAMP; CHROMATIN; COMPLEX; TRANSLOCATION; ASSOCIATION AB Brd4 is a mammalian protein that contains a double bromodomain. It binds to chromatin and regulates cell cycle progression at multiple stages. By immunopurification and mass spectrometry, we identified a Rap GTPase-activating protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence complementation revealed that Brd4 and SPA-1 interact with each other in the nucleus of living cells. Supporting the functional importance of the interaction, Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1 and Brd4 redirected subcellular localization of the partner and disrupted normal cell cycle progression. These effects were, however, reversed by coexpression of the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G, is required for cell division. This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto, Japan. Baylor Coll Med, Dept Biochem & Cell Biol, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. EM ozatok@nih.gov NR 42 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2004 VL 24 IS 20 BP 9059 EP 9069 DI 10.1128/MCB.24.20.9059-9069.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 859CG UT WOS:000224239100024 PM 15456879 ER PT J AU Taylor-Harding, B Binne, UK Korenjak, M Brehm, A Dyson, NJ AF Taylor-Harding, B Binne, UK Korenjak, M Brehm, A Dyson, NJ TI p55 the Drosophila ortholog of RbAp46/RbAp48, is required for the repression of dE2F2/RBF-regulated genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT TRANSCRIPTIONAL REPRESSION; TUMOR-SUPPRESSOR PROTEIN; CELL-CYCLE PROGRESSION; HISTONE DEACETYLASE; RETINOBLASTOMA PROTEIN; MICROARRAY ANALYSIS; FAMILY PROTEINS; DNA-REPLICATION; E2F PROTEINS; IN-VIVO AB Many proteins have been proposed to be involved in retinoblastoma protein (pRB)-mediated repression, but it is largely uncertain which cofactors are essential for pRB to repress endogenous E2F-regulated promoters. Here we have taken advantage of the stream-lined Drosophila dE2F/RBF pathway, which has only two E2Fs (dE2F1 and dE2F2), and two pRB family members (RBF1 and RBF2). With RNA interference (RNAi), we depleted potential corepressors and looked for the elevated expression of groups of E2F target genes that are known to be directly regulated by RBF1 and RBF2. Previous studies have implicated histone deacetylase (HDAC) and SWI/SNF chromatin-modifying complexes in pRB-mediated repression. However, our results fail to support the idea that the SWI/SNF proteins are required for RBF-mediated repression and suggest that a requirement for HDAC activities is likely to be limited to a subset of targets. We found that the chromatin assembly factor p55/dCAF-1 is essential for the repression of dE2F2-regulated targets. The removal of p55 deregulated the expression of E2F targets that are normally repressed by dE2F2/RBF1 and dE2F2/RBF2 complexes in a cell cycle-independent manner but had no effect on the expression of E2F targets that are normally coupled with cell proliferation. The results indicate that the mechanisms of RBF regulation at these two types of E2F targets are different and suggest that p55, and perhaps p55's mammalian orthologs RbAp46 and RbAp48, have a conserved function in repression by pRB-related proteins. C1 Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. Univ Munich, Adolf Butenandt Inst, Lehrstuhl Mol Biol, Munich, Germany. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Bldg 149,13th St, Charlestown, MA 02139 USA. EM dyson@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM53203, R01 GM053203] NR 68 TC 48 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2004 VL 24 IS 20 BP 9124 EP 9136 DI 10.1128/MCB.24.20.9124-9136.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 859CG UT WOS:000224239100029 PM 15456884 ER PT J AU Frohlich, LF Gensure, RC Schipani, E Juppner, H Bastepe, M AF Frohlich, LF Gensure, RC Schipani, E Juppner, H Bastepe, M TI Haplotype frequencies and linkage disequilibrium analysis of four frequent polymorphisms at the PTH/PTH-related peptide receptor gene locus SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PTH/PTH-related peptide receptor; parathyroid hormone; single nucleotide polymorphism; linkage disequilibrium; bone metabolism; bone mineralization ID PARATHYROID-HORMONE; METAPHYSEAL CHONDRODYSPLASIA; PTHRP RECEPTOR; OSTEOPOROSIS AB The parathyroid hormone (PTH)/PTH-related peptide receptor is a critical component in the control of mineral ion metabolism and in bone development. This receptor is encoded by a single gene (PTHRI) on chromosome 3p21.1-p24.2, and mutations in this gene have been found in several clinical disorders of bone and mineral metabolism. To facilitate future genetic studies of this important gene, we determined haplotype frequencies and performed linkage disequilibrium (LD) analysis of four different polymorphisms at the PTHRI locus. Combined analysis of Caucasian, African-American and Asian individuals indicated that LD exists between all but one pair of the four polymorphisms. However, the pattern of LD differed substantially among the three subpopulations; for example, LD between two closely spaced (154-by apart) single nucleotide polymorphisms appeared to be present only in Asians. Depending on the population under study, genetic association studies may need to test even more closely spaced polymorphic markers when screening the PTHRI locus. These findings may thus affect the design and interpretation of future genetic studies involving PTHRI. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit,Dept Med, Boston, MA 02114 USA. RP Bastepe, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit,Dept Med, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-062973-01A1, DK-50708-01] NR 18 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 2004 VL 18 IS 5 BP 353 EP 357 DI 10.1016/j.mcp.2004.05.005 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 848SI UT WOS:000223487000011 PM 15294324 ER PT J AU Bonilla, L Richmond, T Sutton, J Fenyo, D Maroto, F Sarracino, D Woo, J Weiner, R Liu, E Gerszten, R AF Bonilla, Leo Richmond, Tori Sutton, Jennifer Fenyo, David Maroto, Fernando Sarracino, David Woo, Jennifer Weiner, Rory Liu, Emerson Gerszten, Robert TI Differential expression analysis of the human plasma proteome following myocardial infarction using direct LC-MSn measurement for protein ID and quantification SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Bonilla, Leo; Richmond, Tori; Sutton, Jennifer; Maroto, Fernando] Thermo Electron Corp, Biomarkers Discovery Program, Boston, MA USA. [Sarracino, David] Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. [Weiner, Rory; Liu, Emerson; Gerszten, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Weiner, Rory; Liu, Emerson; Gerszten, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S213 EP S213 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200515 ER PT J AU Liu, E Bonilla, L Richmond, T Sutton, J Fenyo, D Marot, F Sarracino, D Wool, J Weiner, R Gerszten, RE AF Liu, Emerson Bonilla, Leo Richmond, Tori Sutton, Jennifer Fenyo, David Marot, Fernando Sarracino, David Wool, Jennifer Weiner, Rory Gerszten, Robert E. TI Novel markers of myocardial injury SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Bonilla, Leo; Richmond, Tori; Sutton, Jennifer; Marot, Fernando] Thermo Elect Corp, Biomarkers Dicovery Program, Boston, MA USA. [Sarracino, David] Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. [Fenyo, David] GE Healthcare, Cambridge, MA USA. [Liu, Emerson; Wool, Jennifer; Weiner, Rory; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Liu, Emerson; Wool, Jennifer; Weiner, Rory; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Liu, Emerson; Wool, Jennifer; Weiner, Rory; Gerszten, Robert E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S9 EP S9 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200022 ER PT J AU Lu, XM Fischman, A Avruch, J Tompkins, RG AF Lu, Xiao-Ming Fischman, Alan Avruch, Joseph Tompkins, Ronald G. TI Site-specific detection of phosphorylation and S-nitrosylation using capillary liquid chromatography interfaced with Q-TOF mass spectrometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Lu, Xiao-Ming; Fischman, Alan; Tompkins, Ronald G.] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Fischman, Alan] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Lu, Xiao-Ming; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S132 EP S132 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200334 ER PT J AU Richmond, T Bonilla, L Gerszten, R Liu, E Sutton, J Sarracino, D AF Richmond, Tori Bonilla, Leo Gerszten, Robert Liu, Emerson Sutton, Jennifer Sarracino, David TI Methodology for sample handling and separation of human plasma for differential expression analysis in serial samples from patients with myocardial infarction SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Richmond, Tori; Bonilla, Leo; Liu, Emerson; Sutton, Jennifer] Thermo Electron Corp, Biomarkers Discovery Program, Boston, MA USA. [Gerszten, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gerszten, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Sarracino, David] Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S138 EP S138 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200344 ER PT J AU Sutton, JN Bonilla, L Richmond, T Gerszten, RE Liu, E Senko, M Zabrouskov, V Kelleher, NL AF Sutton, Jennifer N. Bonilla, Leo Richmond, Tori Gerszten, Robert E. Liu, Emerson Senko, Michael Zabrouskov, Vlad Kelleher, Neil L. TI Top-down analysis of low molecular weight human plasma Proteome using hybrid ion Trap-Fourier transform mass Spectrometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Sutton, Jennifer N.; Bonilla, Leo; Richmond, Tori] Thermo Electron Corp, Biomarkers Discovery Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Senko, Michael; Zabrouskov, Vlad] Thermo Electron Corp, San Jose, CA USA. [Kelleher, Neil L.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S141 EP S141 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200351 ER PT J AU Sajan, MP Standaert, ML Miura, A Kahn, CR Farese, RV AF Sajan, MP Standaert, ML Miura, A Kahn, CR Farese, RV TI Tissue-specific differences in activation of atypical protein kinase C and protein kinase B in muscle, liver, and adipocytes of insulin receptor substrate-1 knockout mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID STIMULATED GLUCOSE-TRANSPORT; TRANSCRIPTION FACTOR FKHR; SKELETAL-MUSCLE; HEART 6-PHOSPHOFRUCTO-2-KINASE; PHOSPHOINOSITIDE 3-KINASE; DEFECTIVE ACTIVATION; GLUT4 TRANSLOCATION; PROMOTER ACTIVITY; BROWN ADIPOCYTES; RAT ADIPOCYTES AB Insulin receptor substrates (IRSs) 1 and 2 are postulated to control the activation of phosphatidylinositol 3-kinase (PI3K)-dependent signaling factors, namely, atypical protein kinase C ( aPKC) and protein kinase B (PKB)/Akt, which mediate metabolic effects of insulin. However, it is uncertain whether aPKC and PKB are activated together or differentially in response to IRS-1 and IRS-2 activation in insulin-sensitive tissues. Presently, we examined insulin activation of aPKC and PKB in vastus lateralis muscle, adipocytes, and liver in wild-type and IRS-1 knockout mice, and observed striking tissue-specific differences. In muscle of IRS-1 knockout mice, the activation of both aPKC and PKB was markedly diminished. In marked contrast, only aPKC activation was diminished in adipocytes, and only PKB activation was diminished in liver. These results suggest that IRS-1 is required for: 1) activation of both aPKC and PKB in muscle; 2) aPKC, but not PKB, activation in adipocytes; and 3) PKB, but not aPKC, activation in liver. Presumably, IRS-2 or other PI3K activators account for the normal activation of aPKC in liver and PKB in adipocytes of IRS-1 knockout mice. These complexities in aPKC and PKB activation may be relevant to metabolic abnormalities seen in tissues in which IRS-1 or IRS-2 is specifically or predominantly down-regulated. C1 James A Haley Vet Hosp, Res Serv, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Farese, RV (reprint author), James A Haley Vet Hosp, Res Serv, ACOS-151,13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM rfarese@hsc.usf.edu RI Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [DK-38079-09A1, DK33201, DK55545, R01 DK065969] NR 40 TC 31 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2004 VL 18 IS 10 BP 2513 EP 2521 DI 10.1210/me.2004-0045 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 856DW UT WOS:000224025200013 PM 15256535 ER PT J AU Mylonakis, E Idnurm, A Moreno, R El Khoury, J Rottman, JB Ausubel, FM Heitman, J Calderwood, SB AF Mylonakis, E Idnurm, A Moreno, R El Khoury, J Rottman, JB Ausubel, FM Heitman, J Calderwood, SB TI Cryptococcus neoformans Kin1 protein kinase homologue, identified through a Caenorhabditis elegans screen, promotes virulence in mammals SO MOLECULAR MICROBIOLOGY LA English DT Article ID DROSOPHILA-MELANOGASTER; PHAGOCYTOSIS; MACROPHAGES; POLARITY; HOST; GENE; INFECTION; PATHOGEN; GROWTH; CELLS AB Cryptococcal infections are a global cause of significant morbidity and mortality. Recent studies support the hypothesis that virulence of Cryptococcus neoformans may have evolved via survival selection in environmental hosts, such as amoebae and free-living nematodes. We used killing of the nematode Caenorhabditis elegans by C. neoformans as an assay to screen a library of random C. neoformans insertion mutants. Of 350 mutants tested, seven were identified with attenuated virulence that persisted after crossing the mutation back into a wild-type strain. Genetic analysis of one strain revealed an insertion in a gene homologous to Saccharomyces cerevisiae KIN1, which encodes a serine/threonine protein kinase. C. neoformans kin1 mutants exhibited significant defects in virulence in murine inhalation and haematogenous infection models and displayed increased binding to alveolar and peritoneal macrophages. The kin1 mutant phenotypes were complemented by the wild-type KIN1 gene. These findings show that the C. neoformans Kin1 kinase homologue is required for full virulence in disparate hosts and that C. elegans can be used as a substitute host to identify novel factors involved in fungal pathogenesis in mammals. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Archemix Corp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM scalderwood@partners.org RI Idnurm, Alexander/K-8558-2013 OI Idnurm, Alexander/0000-0001-5995-7040 FU NIAID NIH HHS [AI44975]; NIGMS NIH HHS [GM48707] NR 47 TC 57 Z9 60 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2004 VL 54 IS 2 BP 407 EP 419 DI 10.1111/j.1365-2958.2004.04310.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 861EH UT WOS:000224398400012 PM 15469513 ER PT J AU Nishikawa, K Yoshimura, F Duncan, MJ AF Nishikawa, K Yoshimura, F Duncan, MJ TI A regulation cascade controls expression of Porphyromonas gingivalis fimbriae via the FimR response regulator SO MOLECULAR MICROBIOLOGY LA English DT Article ID INFECTED ENDOTHELIAL-CELLS; GENES DOWNSTREAM; EPITHELIAL-CELLS; VIBRIO-CHOLERAE; PROMOTER; PROTEIN; ACTIVATION; VIRULENCE; BINDING; IDENTIFICATION AB Little is known about how Porphyromonas gingivalis, a Gram-negative oral anaerobe, senses environmental changes, and how such information is transmitted to the cell. The production of P. gingivalis surface fimbriae is regulated by FimS-FimR, a two component signal transduction system. Expression of fimA, encoding the fimbrilin protein subunit of fimbriae, is positively regulated by the FimR response regulator. In this study we investigated the molecular mechanisms of FimR regulation of fimA expression. Comparative transcription profiling of fimR wild-type and mutant strains shows that FimR controls the expression of several genes including five clustered around the fimA locus. Chromatin immunoprecipitation assays and electrophoretic mobility shift assays identify and confirm that FimR binds to the promoter region of the first gene in the fimA cluster. Gene expression analyses of mutant strains reveal a transcriptional cascade involving multiple steps, with FimR activating expression of the first gene of the cluster that encodes a key regulatory protein. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Nagoya, Aichi 4648650, Japan. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. EM mduncan@forsyth.org FU NIDCR NIH HHS [DE10510, DE12082] NR 40 TC 42 Z9 43 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2004 VL 54 IS 2 BP 546 EP 560 DI 10.1111/j.1365-2958.2004.04291.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 861EH UT WOS:000224398400022 PM 15469523 ER PT J AU Oehmig, A Fraefel, C Breakefield, XO AF Oehmig, A Fraefel, C Breakefield, XO TI Update on herpesvirus amplicon vectors SO MOLECULAR THERAPY LA English DT Review ID SIMPLEX-VIRUS TYPE-1; EPSTEIN-BARR-VIRUS; BACTERIAL ARTIFICIAL CHROMOSOME; GREEN FLUORESCENT PROTEIN; MEDIATED GENE-TRANSFER; CHRONIC LYMPHOCYTIC-LEUKEMIA; SITE-SPECIFIC RECOMBINATION; CENTRAL-NERVOUS-SYSTEM; HOST-SHUTOFF FUNCTION; IN-VIVO C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Univ Zurich, Inst Virol, Zurich, Switzerland. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu NR 152 TC 39 Z9 39 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2004 VL 10 IS 4 BP 630 EP 643 DI 10.1016/j.ymthe.2004.06.641 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 869DY UT WOS:000224964800009 PM 15451447 ER PT J AU Betancourt, JR Maina, AW AF Betancourt, JR Maina, AW TI The Institute of Medicine Report "Unequal treatment": Implications for academic health centers SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Department of Medicine Grand Round Conference CY 2003 CL New York, NY SP Mt Sinai Sch Med DE Institute of Medicine Report; unequal treatment; racial disparities; ethnic disparities; health care; racial minorities; ethnic minorities; minority health; academic health centers ID SPANISH-SPEAKING PATIENTS; RACIAL-DIFFERENCES; DECISION-MAKING; CARE; LANGUAGE; ETHNICITY; EMERGENCY; RACE; MANAGEMENT; ACCESS AB Background. The United States has achieved dramatic improvements in overall health and life expectancy, largely due to initiatives in public health, health promotion and disease prevention. Academic health centers have played a major role in this effort, given their mission of engaging in research, educating health professionals, providing primary and specialty medical services, and caring for the poor and uninsured. However, national data indicate that minority Americans have poorer health outcomes (compared to whites) from preventable and treatable conditions such as cardiovascular disease, diabetes, asthma, cancer and HIV/AIDS. Two factors contribute heavily to these racial and ethnic disparities in health: minorities are subjected to adverse social determinants, and they are disproportionately represented among the uninsured. In the last twenty years, however, the literature has highlighted the fact that racial and ethnic disparities occur not only in health, but also in health care. The Institute of Medicine Report, "Unequal Treatment." The Institute of Medicine (IOM) was asked to determine the extent of racial and ethnic disparities in health care. Their report, entitled "Unequal Treatment," found that racial and ethnic disparities in health care do exist, and that many sources, including health care systems, health care providers, patients and utilization managers, are contributors. Recommendations from "Unequal Treatment": Implications for Academic Health Centers. The IOM Report, "Unequal Treatment," provides a series of recommendations to address racial and ethnic disparities in health care, targeted to a broad audience (the executive summary and full IOM Report can be found at www.nap.edu under the search heading "Unequal Treatment"). Several of the recommendations speak directly to the mission and roles of academic health centers, and have clear and direct implications for patient care, education, and research. These recommendations include collecting and reporting health care access and utilization data by patient's race/ethnicity, encouraging the use of evidence-based guidelines and quality improvement, supporting the use of language interpretation services in the clinical setting, increasing awareness of racial/ethnic disparities in health care, increasing the proportion of underrepresented. minorities in the health care workforce, integrating cross-cultural education into the training of all health care professionals, and conducting further research to identify sources of disparities and promising interventions. Conclusion: "Unequal Treatment" provides the first detailed, systematic examination of racial/ethnic disparities in health care, and provides a blueprint for how to address them. The report's recommendations are broad in scope, yet have direct implications for academic health centers. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Betancourt, JR (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor,Suite 901, Boston, MA 02114 USA. NR 50 TC 56 Z9 56 U1 1 U2 9 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD OCT PY 2004 VL 71 IS 5 BP 314 EP 321 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 864QI UT WOS:000224647600004 PM 15543432 ER PT J AU Handforth, A Martin, FC AF Handforth, A Martin, FC TI Pilot efficacy and tolerability: A randomized, placebo-controlled trial of levetiracetam for essential tremor SO MOVEMENT DISORDERS LA English DT Article DE essential tremor; levetiracetam; clinical trial ID ANTIEPILEPTIC DRUG LEVETIRACETAM; DOUBLE-BLIND; PROPRANOLOL; GABAPENTIN; MYOCLONUS; DESIGNS; BRAIN AB The purpose of this pilot single-site study was to assess efficacy and safety of levetiracetam for essential tremor, using a placebo-controlled, double-blind, randomized crossover design with an interim analysis planned after completion of the first 10 to 15 subjects. The study was designed to detect a mean 30% reduction in composite tremor score, comparable to that of primidone or propranolol, which can be demonstrated with 30 or fewer subjects. Each treatment arm included baseline tremor assessments, a 4-week medication titration, 2 weeks of stable dose, and treatment tremor assessments. Levetiracetam was titrated to 3,000 mg/day or to a lower maximal tolerated dose. The median age was 72 years, with 28 years median tremor duration. There was no statistically significant difference in response between placebo and levetiracetam on any tremor rating scale or accelerometry measure. The 95 % confidence interval for the true mean difference between placebo and levetiracetarn treatments was +18.5 to -22.5%, which excludes the minimum 30% drop required to consider levetiracetam clinically effective to a degree comparable to primidone or propranolol. Whether levetiracetam has lesser-degree antitremor efficacy was not addressed in this pilot study. (C) 2004 Movement Disorder Society. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv W127, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM charles.handforth@med.va.gov NR 29 TC 33 Z9 33 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2004 VL 19 IS 10 BP 1215 EP 1221 DI 10.1002/mds.20147 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 861MY UT WOS:000224422000013 PM 15390011 ER PT J AU Shefner, JM Cudkowicz, ME Zhang, H Schoenfeld, D Jillapalli, D AF Shefner, JM Cudkowicz, ME Zhang, H Schoenfeld, D Jillapalli, D CA Northeast ALS Consortium TI The use of statistical mune in a multicenter clinical trial SO MUSCLE & NERVE LA English DT Article; Proceedings Paper CT 10th International Symposium on ALS/MND CY JAN 16, 2003 CL MUNICH, GERMANY DE amyotrophic lateral sclerosis; clinical trial; motor unit; motor unit number estimation; statistical MUNE ID AMYOTROPHIC-LATERAL-SCLEROSIS; UNIT NUMBER ESTIMATION; MOTOR UNITS; PERIPHERAL-NERVE; ALS; REPRODUCIBILITY; INVOLVEMENT; CONDUCTION; SURVIVAL; MUSCLE AB Techniques to estimate motor unit number (MUNE) measure the number of functioning motor units in a muscle. In diseases characterized by progressive motor unit loss, such as amyotrophic lateral sclerosis (ALS), MUNE may be useful to monitor disease progression or beneficial response to treatment. As part of a multicenter, placebo-controlled, randomized, double-blind clinical trial testing the efficacy of creatine in patients with ALS, statistical MUNE was measured in 104 patients tested monthly for 6 months. The objective was to determine whether MUNE was a reliable and sensitive outcome measure in the context of a multicenter trial. Formal training and reliability testing was required for all MUNE evaluators. Testing of normal controls showed a high degree of test-retest reliability. All patient data were combined as the experimental treatment showed no efficacy. There was a 23% decline in MUNE over 6 months. The technique as employed in this trial overemphasized the presence of small motor units; this problem was partially addressed by poststudy data monitoring and censuring. Thus, MUNE can be used reliably as an outcome measure in multicenter clinical trials; specific remedies are suggested for the difficulties encountered in this study. C1 SUNY, Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. RP Shefner, JM (reprint author), SUNY, Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. EM shefner@upstate.edu NR 22 TC 64 Z9 66 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2004 VL 30 IS 4 BP 463 EP 469 DI 10.1002/mus.20120 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 857LA UT WOS:000224116900009 PM 15316983 ER PT J AU ElShamy, WM Livingston, DM AF ElShamy, WM Livingston, DM TI Identification of BRCA1-IRIS, a BRCA1 locus product SO NATURE CELL BIOLOGY LA English DT Article ID REPLICATION INITIATION SITES; SUPPRESSOR GENE BRCA1; BREAST-CANCER; DNA-REPLICATION; MESSENGER-RNA; INTRON RETENTION; SPLICE VARIANT; MAMMARY-GLAND; START SITES; HUMAN-CELLS AB Breast cancer is the most common malignancy among women, and mutations in the BRCA genes produce increased susceptibility to these malignancies in certain families. Here we identify BRCA1-IRIS as a 1,399-amino-acid BRCA1 gene product encoded by an uninterrupted open reading frame that extends from codon 1 of the known BRCA1 open reading frame to a termination point 34 triplets into intron 11. Unlike full-length BRCA1 (p220), BRCA1-IRIS is exclusively chromatin-associated, fails to interact with BARD1 in vivo or in vitro and exhibits unique nuclear immunostaining. Unlike BRCA1FL (or p220), BRCA1-IRIS also co-immunoprecipitated with DNA-replication-licensing proteins and with known replication initiation sites. Suppression of BRCA1-IRIS expression hindered the normal departure of geminin from pre-replication complexes, and depressed the rate of cellular DNA replication and possibly initiation-related synthesis. In contrast, BRCA1-IRIS overexpression stimulated DNA replication. These data imply that endogenous BRCA1-IRIS positively influences the DNA replication initiation machinery. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP ElShamy, WM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM wael_elshamy@dfci.harvard.edu; david_livingston@dfci.harvard.edu NR 53 TC 55 Z9 59 U1 5 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2004 VL 6 IS 10 BP 954 EP + DI 10.1038/ncb1171 PG 18 WC Cell Biology SC Cell Biology GA 859FY UT WOS:000224250000010 PM 15448696 ER PT J AU Mansfield, JH Harfe, BD Nissen, R Obenauer, J Srineel, J Chaudhuri, A Farzan-Kashani, R Zuker, M Pasquinelli, AE Ruvkun, G Sharp, PA Tabin, CJ McManus, MT AF Mansfield, JH Harfe, BD Nissen, R Obenauer, J Srineel, J Chaudhuri, A Farzan-Kashani, R Zuker, M Pasquinelli, AE Ruvkun, G Sharp, PA Tabin, CJ McManus, MT TI MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression SO NATURE GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; MESSENGER-RNA; GENES; IDENTIFICATION; DROSOPHILA; CLEAVAGE; ELEMENT; DOMAIN; MOUSE; MIRNA AB MicroRNAs (miRNAs) are a class of short (similar to22-nt) noncoding RNA molecules that downregulate expression of their mRNA targets. Since their discovery as regulators of developmental timing in Caenorhabditis elegans, hundreds of miRNAs have been identified in both animals and plants(1). Here, we report a technique for visualizing detailed miRNA expression patterns in mouse embryos. We elucidate the tissue-specific expression of several miRNAs during embryogenesis, including two encoded by genes embedded in homeobox (Hox) clusters, miR-10a and miR-196a. These two miRNAs are expressed in patterns that are markedly reminiscent of those of Hox genes. Furthermore, miR-196a negatively regulates Hoxb8, indicating that its restricted expression pattern probably reflects a role in the patterning function of the Hox complex. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA. Rensselaer Polytech Inst, Dept Math Sci, Troy, NY 12180 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. MIT, NcGovern Inst, Dept Biol, Cambridge, MA 02139 USA. RP Tabin, CJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM tabin@genetics.med.harvard.edu; mmcmanus@diabetes.ucsf.edu NR 27 TC 303 Z9 328 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2004 VL 36 IS 10 BP 1079 EP 1083 DI 10.1038/ng1421 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 857YN UT WOS:000224156500016 PM 15361871 ER PT J AU Graux, C Cools, J Melotte, C Quentmeier, H Ferrando, A Levine, R Vermeesch, JR Stul, M Dutta, B Boeckx, N Bosly, A Heimann, P Uyttebroeck, A Mentens, N Somers, R MacLeod, RAF Drexler, HG Look, AT Gilliland, DG Michaux, L Vandenberghe, P Wlodarska, I Marynen, P Hagemeijer, A AF Graux, C Cools, J Melotte, C Quentmeier, H Ferrando, A Levine, R Vermeesch, JR Stul, M Dutta, B Boeckx, N Bosly, A Heimann, P Uyttebroeck, A Mentens, N Somers, R MacLeod, RAF Drexler, HG Look, AT Gilliland, DG Michaux, L Vandenberghe, P Wlodarska, I Marynen, P Hagemeijer, A TI Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia SO NATURE GENETICS LA English DT Article ID DOUBLE-MINUTE CHROMOSOMES; TYROSINE KINASE; MYELOID LEUKEMIAS; GENES; PROTEIN; TRANSLOCATION; AMPLIFICATION; EXPRESSION; DELETIONS; IMATINIB AB In T-cell acute lymphoblastic leukemia (T-ALL), transcription factors are known to be deregulated by chromosomal translocations, but mutations in protein tyrosine kinases have only rarely been identified(1-3). Here we describe the extrachromosomal (episomal)(4) amplification of ABL1 in 5 of 90 (5.6%) individuals with T-ALL, an aberration that is not detectable by conventional cytogenetics. Molecular analyses delineated the amplicon as a 500-kb region from chromosome band 9q34, containing the oncogenes ABL1 and NUP214 (refs.(5,6)). We identified a previously undescribed mechanism for activation of tyrosine kinases in cancer: the formation of episomes resulting in a fusion between NUP214 and ABL1. We detected the NUP214-ABL1 transcript in five individuals with the ABL1 amplification, in 5 of 85 (5.8%) additional individuals with T-ALL and in 3 of 22 T-ALL cell lines. The constitutively phosphorylated tyrosine kinase NUP214-ABL1 is sensitive to the tyrosine kinase inhibitor imatinib(7,8). The recurrent cryptic NUP214-ABL1 rearrangement is associated with increased HOX expression(1) and deletion of CDKN2A(9), consistent with a multistep pathogenesis of T-ALL. NUP214-ABL1 expression defines a new subgroup of individuals with T-ALL who could benefit from treatment with imatinib. C1 Univ Leuven, Dept Human Genet, Louvain, Belgium. Univ Leuven, Dept Hematol, Louvain, Belgium. Flanders Interuniv Inst Biotechnol, Dept Human Genet, Louvain, Belgium. German Collect Microorganisms & Cell Cultures, Braunschweig, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Flanders Interuniv Inst Biotechnol, Microarray Facil, Louvain, Belgium. Clin Univ UCL Mt Godinne, Dept Hematol, Brussels, Belgium. Free Univ Brussels, Erasme Hosp, Dept Med Genet, B-1050 Brussels, Belgium. Univ Leuven, Dept Pediat Hematooncol, Louvain, Belgium. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA USA. St Luc, Brussels, Belgium. RP Marynen, P (reprint author), Univ Leuven, Dept Human Genet, Louvain, Belgium. EM peter.marynen@med.kuleuven.ac.be; anne.hagemeijer@med.kuleuven.ac.be OI Vandenberghe, Peter/0000-0003-4719-1935; Cools, Jan/0000-0001-6626-5843 NR 27 TC 233 Z9 239 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2004 VL 36 IS 10 BP 1084 EP 1089 DI 10.1038/ng1425 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 857YN UT WOS:000224156500017 PM 15361874 ER PT J AU Carroll, MC AF Carroll, MC TI The complement system in regulation of adaptive immunity SO NATURE IMMUNOLOGY LA English DT Review ID FOLLICULAR DENDRITIC CELLS; CLASSICAL PATHWAY COMPLEMENT; ANAPHYLATOXIN C3A RECEPTOR; INFLUENZA-VIRUS INFECTION; TH2 EFFECTOR FUNCTIONS; HERPES-SIMPLEX-VIRUS; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; NATURAL ANTIBODY; HUMORAL RESPONSE AB The serum complement system, which represents a chief component of innate immunity, not only participates in inflammation but also acts to enhance the adaptive immune response. Specific activation of complement via innate recognition proteins or secreted antibody releases cleavage products that interact with a wide range of cell surface receptors found on myeloid, lymphoid and stromal cells. This intricate interaction among complement activation products and cell surface receptors provides a basis for the regulation of both B and T cell responses. This review highlights fundamental events, explaining how complement links innate and adaptive immunity as well as describing more recent studies on how this large family of proteins functions locally in peripheral lymph nodes to enhance B and T cell responses. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu FU NIAID NIH HHS [AI53570-02, AI36389-08, AI39246-09, AI52343-03] NR 80 TC 526 Z9 546 U1 10 U2 64 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2004 VL 5 IS 10 BP 981 EP 986 DI 10.1038/ni1113 PG 6 WC Immunology SC Immunology GA 857YO UT WOS:000224156600004 PM 15454921 ER PT J AU Jaeckel, E Lipes, MA von Boehmer, H AF Jaeckel, E Lipes, MA von Boehmer, H TI Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes SO NATURE IMMUNOLOGY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; REGULATORY T-CELLS; NOD MICE; IN-VIVO; INSULIN EXPRESSION; TRANSGENIC MICE; IMMUNE-RESPONSE; HUMAN THYMUS; IDDM2 LOCUS; B CHAIN AB Although autoimmune diseases can be initiated by immunization with a single antigen, it is not clear whether a single self antigen is essential for the initiation and, perhaps, the perpetuation of spontaneous autoimmunity. Some studies have suggested that insulin may represent an essential autoantigen in type 1 diabetes. Here we show that unlike tolerance to glutamic acid decarboxylase, tolerance to transgenically overexpressed preproinsulin 2 substantially reduced the onset and severity of type 1 diabetes in nonobese diabetic mice. However, some mice still developed type 1 diabetes, suggesting that insulin is a key, but not absolutely essential, autoantigen. The results are consistent with the idea that the human IDDM2 locus controls susceptibility to type 1 diabetes by regulating intrathymic preproinsulin expression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr, Boston, MA 02215 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu FU NIAID NIH HHS [N01-AI-75320] NR 48 TC 95 Z9 96 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2004 VL 5 IS 10 BP 1028 EP 1035 DI 10.1038/ni1120 PG 8 WC Immunology SC Immunology GA 857YO UT WOS:000224156600026 PM 15378058 ER PT J AU Patti, ME Kahn, BB AF Patti, ME Kahn, BB TI Nutrient sensor links obesity with diabetes risk SO NATURE MEDICINE LA English DT Editorial Material ID ADIPOSE-TISSUE; INSULIN ACTION; TARGET; ACIDS; MICE AB Overeating can lead to the development of insulin resistance and diabetes. A component of the mTOR nutrient signaling pathway now bridges the mechanistic gap between obesity and insulin resistance. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu; bkahn@bidmc.harvard.edu NR 16 TC 38 Z9 40 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2004 VL 10 IS 10 BP 1049 EP 1050 DI 10.1038/nm1004-1049 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 859EM UT WOS:000224245800023 PM 15459705 ER PT J AU Lleo, A Berezovska, O Herl, L Raju, S Deng, A Bacskai, BJ Frosch, MP Irizarry, M Hyman, BT AF Lleo, A Berezovska, O Herl, L Raju, S Deng, A Bacskai, BJ Frosch, MP Irizarry, M Hyman, BT TI Nonsteroidal anti-inflammatory drugs lower A beta(42) and change presenilin 1 conformation SO NATURE MEDICINE LA English DT Article ID GAMMA-SECRETASE; ALZHEIMERS-DISEASE; INHIBITORS; COMPLEX; NSAIDS; MODEL AB Recent reports suggest that some commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) unexpectedly shift the cleavage products of amyloid precursor protein (APP) to shorter, less fibrillogenic forms, although the underlying mechanism remains unknown. We now demonstrate, using a fluorescence resonance energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the proximity between APP and presenilin 1 and alter presenilin 1 conformation both in vitro and in vivo, suggesting a novel allosteric mechanism of action. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [AG15379]; NIBIB NIH HHS [EB00768] NR 12 TC 153 Z9 162 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2004 VL 10 IS 10 BP 1065 EP 1066 DI 10.1038/nm1112 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 859EM UT WOS:000224245800035 PM 15448688 ER PT J AU Yu, LQ Huang, ZH Mariani, J Wang, YM Moskowitz, M Chen, JF AF Yu, LQ Huang, ZH Mariani, J Wang, YM Moskowitz, M Chen, JF TI Selective inactivation or reconstitution of adenosine A(2A) receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury SO NATURE MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; AGONIST REDUCES PARALYSIS; SPINAL-CORD ISCHEMIA; CEREBRAL-ISCHEMIA; INDUCED EXCITOTOXICITY; NEUROPROTECTIVE ROLE; PARKINSONS-DISEASE; A(1) RECEPTOR; MOTOR-NEURONS; PROTECTION AB Inactivation of the adenosine A(2A) receptor (A(2A)R) consistently protects against ischemic brain injury and other neural insults, but the relative contribution of A(2A) Rs on peripheral inflammatory cells versus A(2A) Rs expressed on neurons and glia is unknown. We created a chimeric mouse model in which A(2A) Rs on bone marrow-derived cells (BMDCs) were selectively inactivated or reconstituted by bone marrow transplantation. Selective reconstitution of A(2A) Rs on BMDCs (A(2A) R knockout mice transplanted with wild-type bone marrow cells) largely reinstates ischemic brain injury in global A(2A) R knockout mice. Conversely, selective inactivation of A(2A) Rs on BMDCs (wild-type mice transplanted with A(2A) R knockout bone marrow cells) attenuates infarct volumes and ischemia-induced expression of several proinflammatory cytokines in the brain, but exacerbates ischemic liver injury. These results indicate that the A(2A) R-stimulated cascade in BMDCs is an important modulator of ischemic brain injury and that ischemic brain and liver injuries are regulated distinctly by A(2A) Rs on BMDCs. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Chen, JF (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,C329, Boston, MA 02118 USA. EM chenjf@bu.edu RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS-10828, NS37403, NS41083] NR 50 TC 89 Z9 96 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2004 VL 10 IS 10 BP 1081 EP 1087 DI 10.1038/nm1103 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 859EM UT WOS:000224245800038 PM 15448683 ER PT J AU Cohen, T Murray, M AF Cohen, T Murray, M TI Modeling epidemics of multidrug-resistant M-tuberculosis of heterogeneous fitness SO NATURE MEDICINE LA English DT Article ID ANTIBIOTIC-RESISTANCE; TRANSMISSION DYNAMICS; CONTROL STRATEGIES; CHEMOTHERAPY; REINFECTION; COMMUNITY; DISEASE AB Mathematical models have recently been used to predict the future burden of multidrug-resistant tuberculosis (MDRTB)(1-3). These models suggest the threat of multidrug resistance to TB control will depend on the relative `fitness' of MDR strains and imply that if the average fitness of MDR strains is considerably less than that of drug-sensitive strains, the emergence of resistance will not jeopardize the success of tuberculosis control efforts. Multidrug resistance in M. tuberculosis is conferred by the sequential acquisition of a number of different single-locus mutations that have been shown to have heterogeneous phenotypic effects. Here we model the impact of initial fitness estimates on the emergence of MDRTB assuming that the relative fitness of MDR strains is heterogeneous. We find that even when the average relative fitness of MDR strains is low and a well-functioning control program is in place, a small subpopulation of a relatively fit MDR strain may eventually outcompete both the drug-sensitive strains and the less fit MDR strains. These results imply that current epidemiological measures and short-term trends in the burden of MDRTB do not provide evidence that MDRTB strains can be contained in the absence of specific efforts to limit transmission from those with MDR disease. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. RP Murray, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu RI Cohen, Ted/G-8101-2011 FU NIAID NIH HHS [K08 AI055985-02, K08 AI055985] NR 30 TC 147 Z9 154 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2004 VL 10 IS 10 BP 1117 EP 1121 DI 10.1038/nm1110 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 859EM UT WOS:000224245800043 PM 15378056 ER PT J AU Carroll, MC AF Carroll, MC TI A protective role for innate immunity in systemic lupus erythematosus SO NATURE REVIEWS IMMUNOLOGY LA English DT Editorial Material ID CLASSICAL PATHWAY COMPLEMENT; BINDING LECTIN ENGAGEMENT; AUTOREACTIVE B-CELLS; APOPTOTIC CELLS; AUTOANTIBODY PRODUCTION; IGG AUTOANTIBODIES; MICE DEFICIENT; SELF-TOLERANCE; SECRETED IGM; RECEPTORS 1 AB Clinical and genetic studies in humans and animal models indicate a crucial protective role for the complement system in systemic lupus erythematosus (SLE). This presents a paradox because the complement system is considered to be an important mediator of the inflammation that is observed in patients with SLE. One current view is that complement provides protection by facilitating the rapid removal of apoptotic debris to circumvent an autoimmune response. In this Opinion article, I discuss an alternative model in which complement - together with other components of the innate immune system - participates in the 'presentation' of SLE-inducing self-antigens to developing B cells. In this way, the complement system and innate immunity protect against responses to SLE ( self) antigens by enhancing the elimination of self-reactive lymphocytes. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu NR 75 TC 103 Z9 109 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD OCT PY 2004 VL 4 IS 10 BP 825 EP 831 DI 10.1038/nri1456 PG 7 WC Immunology SC Immunology GA 859EK UT WOS:000224245600017 PM 15459673 ER PT J AU Dhe-Sirano, D Werner, ED Masahiro, N Hansen, L Chi, YI Shoelson, SE AF Dhe-Sirano, D Werner, ED Masahiro, N Hansen, L Chi, YI Shoelson, SE TI A phenylalanine zipper mediates APS dimerization SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY PH; ADAPTER PROTEIN APS; INSULIN-RECEPTOR; C-CBL; SIGNAL-TRANSDUCTION; SH2 DOMAINS; LNK; IDENTIFICATION; KINASE; PHOSPHORYLATION AB The APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. We now show that a conserved N-terminal domain mediates APS homodimerization. We determined the crystal structure of the dimerization domain at a resolution of 1.7 Angstrom using bromide ion MAD phasing. Each molecule contributes two helices to a compact four-helix bundle having a bisecting-U topology. Its most conspicuous feature is a stack of interdigitated phenylalanine side chains at the domain core. These residues create a new motif we refer to as a 'phenylalanine zipper', which is critical to dimerization. A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. Dimerization via the phenylalanine zipper domain provides a mechanism for activating and modulating tyrosine kinase activity even in the absence of extracellular ligands. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU NIDDK NIH HHS [R29 DK09393, DK36836, R01 DK43123] NR 47 TC 39 Z9 40 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2004 VL 11 IS 10 BP 968 EP 974 DI 10.1038/nsmb829 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 857NM UT WOS:000224124200018 PM 15378031 ER PT J AU Aghi, M Cohen, K Scadden, D Chiocca, EA AF Aghi, M Cohen, K Scadden, D Chiocca, EA TI The contribution of bone marrow derived cells to glioma blood vessels SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 308 EP 308 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400007 ER PT J AU Demuth, T Rennert, J Hoelzinger, DB Chiocca, AE Deisboeck, T Weiz, D Berens, ME AF Demuth, T Rennert, J Hoelzinger, DB Chiocca, AE Deisboeck, T Weiz, D Berens, ME TI Genetic determinants of glioma invasion in 3D collagen gels SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Translat Genom Res Inst, Phoenix, AZ USA. Ohio State Univ, Med Ctr, James Canc Hosp, Dept Neurosurg, Columbus, OH 43210 USA. Solove Res Inst, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 309 EP 309 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400012 ER PT J AU Mukherjee, N Song, QH Zhai, GG Zhang, M Malhotra, R Latham, DE Delaney, MA Robe, P Nestler, U Loeffler, J Chakravarti, A AF Mukherjee, N Song, QH Zhai, GG Zhang, M Malhotra, R Latham, DE Delaney, MA Robe, P Nestler, U Loeffler, J Chakravarti, A TI Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RI Nestler, Ulf/D-6503-2014 OI Nestler, Ulf/0000-0002-2963-4344 NR 0 TC 0 Z9 0 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 319 EP 319 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400055 ER PT J AU Zhai, G Suzuki, Y Sarkesh, S Black, PM Muzikansky, A Loeffler, JS Chakravarti, A AF Zhai, G Suzuki, Y Sarkesh, S Black, PM Muzikansky, A Loeffler, JS Chakravarti, A TI The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 324 EP 324 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400073 ER PT J AU Chang, SM Barker, FG AF Chang, SM Barker, FG TI Marital status, received treatment, and patient survival in glioblastoma multiforme (GM) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 326 EP 326 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400082 ER PT J AU Kambara, H Okano, H Chiocca, FA Saeki, Y AF Kambara, H Okano, H Chiocca, FA Saeki, Y TI Successful experimental glioma therapy using oncolytic HSV mutant expressing ICP34.5 under control of a nestin promoter SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Keio Univ, Sch Med, Dept Physiol, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 332 EP 332 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400105 ER PT J AU Lamfers, MLM Gianni, D Tang, Y Carette, J Fulci, G Hoebe, EK Saeki, Y Weissleder, R Vandertop, WP Gerritsen, WR Dirven, CMF Chiocca, EA AF Lamfers, MLM Gianni, D Tang, Y Carette, J Fulci, G Hoebe, EK Saeki, Y Weissleder, R Vandertop, WP Gerritsen, WR Dirven, CMF Chiocca, EA TI Monitoring levels and duration of transgene expression from a replication-competent adenovirus using a charged-coupled device camera SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 VU Univ, Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. VU Univ, Med Ctr, Div Gene Therapy, Dept Med Oncol, Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs,Neurosurg Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RI Gerritsen, W.R./H-8031-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 333 EP 333 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400109 ER PT J AU Mohapatra, G Carey, B Gaumont, L Earel, J Berensky, RA Batchelor, TT Louis, DN AF Mohapatra, G Carey, B Gaumont, L Earel, J Berensky, RA Batchelor, TT Louis, DN TI Optimization of DNA labeling from formalin-fixed tissue for BAC array hybridization SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Harvard Univ, Sch Med, Mol Pathol Unit, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Mol Neurooncol Lab, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 339 EP 339 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400133 ER PT J AU Mueller, W Nutt, CL Louis, DN AF Mueller, W Nutt, CL Louis, DN TI The methylome in short-term glioblastoma cell cultures unveiled by 5 ' Aza-dC treatment and microarray analysis SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Nutt, Catherine/K-8794-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 339 EP 339 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400134 ER PT J AU Fulci, G Gianni, D Breymann, LM Fontana, EJ Wakimoto, H Chiocca, EA AF Fulci, G Gianni, D Breymann, LM Fontana, EJ Wakimoto, H Chiocca, EA TI Characterization of inflammatory pathways that limit intratumoral oncolytic virus proliferation SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Massachusetts Gen Hosp, Dept Mol Neurooncol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 341 EP 342 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400144 ER PT J AU Baehring, JM Longtine, J Sklar, J Hochberg, FH AF Baehring, JM Longtine, J Sklar, J Hochberg, FH TI Immunoglobulin heavy chain gene rearrangement analysis in lymphoma of the nervous system SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Yale Univ, Sch Med, New Haven, CT USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 OCT PY 2004 VL 6 IS 4 BP 349 EP 349 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400174 ER PT J AU Tsai, HK Goumnerova, LC Pomeroy, SL Scott, RM Poussaint, TY Xu, R Kieran, MW Tarbell, NJ Marcus, KJ AF Tsai, HK Goumnerova, LC Pomeroy, SL Scott, RM Poussaint, TY Xu, R Kieran, MW Tarbell, NJ Marcus, KJ TI Long-term outcome after treatment of pediatric craniopharyngioma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 364 EP 364 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400232 ER PT J AU Mavrakis, AN Halpern, EF Gonzalez, RG Henson, JW AF Mavrakis, AN Halpern, EF Gonzalez, RG Henson, JW TI Diagnostic evaluation of patients with a brain mass as the presenting manifestation of cancer: Optimization of biopsy site selection SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Harvard Univ, Sch Med,Brain Tumor Ctr, Massachusetts Gen Hosp,Div Neuroradiol, Inst Technol Assessment,Dept Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 367 EP 368 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400245 ER PT J AU Briemberg, HR Richardson, PG Wen, P Esseltine, DL Anderson, K Amato, AA AF Briemberg, HR Richardson, PG Wen, P Esseltine, DL Anderson, K Amato, AA TI A prospective study of bortezomib-induced peripheral neuropathy SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millenium Pharmaceut, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 371 EP 371 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400259 ER PT J AU Cavaliere, R Farace, E Wen, P Schiff, D AF Cavaliere, R Farace, E Wen, P Schiff, D TI Thalidomide-associated thromboembolic events in patients with high-grade gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 372 EP 372 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400263 ER PT J AU Chakravarti, A Seiferheld, W Robins, HI Guha, A Brachman, D Curran, W Choucair, A Mehta, M AF Chakravarti, A Seiferheld, W Robins, HI Guha, A Brachman, D Curran, W Choucair, A Mehta, M TI An update of phase I data from RTOG 0211: A phase I/II clinical study of ZD 1839 (Gefitinib) plus radiation for newly diagnosed glioblastoma (GBM) patients SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Coll Radiol, Philadelphia, PA USA. Univ Wisconsin, Madison, WI USA. Univ Toronto, Toronto, ON, Canada. Fdn Canc Res, Phoenix, AZ USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. LDS Hosp, Salt Lake City, UT USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 372 EP 372 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400264 ER PT J AU Kesari, S Shah, G Xu, R Henson, J Batchelor, TT O'Neill, A Hochberg, FH Levy, B Bradshaw, J Wen, PY AF Kesari, S Shah, G Xu, R Henson, J Batchelor, TT O'Neill, A Hochberg, FH Levy, B Bradshaw, J Wen, PY TI Measuring tumor response in high-grade gliomas in adults SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 377 EP 377 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400283 ER PT J AU Wen, PY Gigas, DC MacDonald, L Batchelor, TT Schiff, D Xu, R Ramakrishna, N Weaver, S Kracher, J Bradshaw, J Levy, B Bailey, E Kesari, S Maher, EA Henson, J Black, PM AF Wen, PY Gigas, DC MacDonald, L Batchelor, TT Schiff, D Xu, R Ramakrishna, N Weaver, S Kracher, J Bradshaw, J Levy, B Bailey, E Kesari, S Maher, EA Henson, J Black, PM TI Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Virginia, Charlottesville, VA USA. Albany Med Ctr, Albany, NY USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 11 Z9 11 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 385 EP 385 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400316 ER PT J AU Wen, PY Yung, WKA Lamborn, K Peng, B Dahia, P Abrey, L Raiser, J Cloughesy, T Fink, K Gilbert, M Chang, S Junck, L Schiff, D Lieberman, F Fine, H Mehta, M Robins, HI DeAngelis, LM Hess, K Groves, M Puduvalli, VK Levin, V Conrad, C Kuhn, J Maher, E Hayes, M Silberman, S Letvak, L Capdeville, R Kaplan, R Murgo, A Stiles, C Prados, MD AF Wen, PY Yung, WKA Lamborn, K Peng, B Dahia, P Abrey, L Raiser, J Cloughesy, T Fink, K Gilbert, M Chang, S Junck, L Schiff, D Lieberman, F Fine, H Mehta, M Robins, HI DeAngelis, LM Hess, K Groves, M Puduvalli, VK Levin, V Conrad, C Kuhn, J Maher, E Hayes, M Silberman, S Letvak, L Capdeville, R Kaplan, R Murgo, A Stiles, C Prados, MD TI Phase I/II study of imatinib mesylate (STI571) for patients with recurrent malignant gliomas (NABTC 99-08) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Univ Texas, MD Anderson Canc Ctr, N Amer Brain Tumor Consortium, Houston, TX 77030 USA. Novartis, E Hanover, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 11 Z9 11 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 385 EP 385 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400315 ER PT J AU Smith, ER Butler, WF Barker, FG AF Smith, ER Butler, WF Barker, FG TI Craniotomy for resection of pediatric brain tumors in the united states 1988-2000: Provider volume-outcome relationships and effects of progressive centralization and specialization of care SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 424 EP 425 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400421 ER PT J AU Zacharoulis, S Turner, C Chi, S Klement, G Ullrich, N Pomeroy, S Marcus, K Goumerova, L Scott, M Proctor, M Kieran, M AF Zacharoulis, S Turner, C Chi, S Klement, G Ullrich, N Pomeroy, S Marcus, K Goumerova, L Scott, M Proctor, M Kieran, M TI Desmoplastic vs. nondesmoplastic medullobastoma: Differences in clinical outcome SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 426 EP 426 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400427 ER PT J AU Young-Poussaint, T Ramamurthy, U Boyett, J Kun, L Kieran, M AF Young-Poussaint, T Ramamurthy, U Boyett, J Kun, L Kieran, M TI Analysis of correlative mri perfusion and diffusion in a phase I trial of the angiogenesis agent SU5416 in children with refractory or progressive brain tumors: A report from the pediatric brain tumor consortium (PBTC) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 435 EP 435 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400466 ER PT J AU Young-Poussaint, T Ramamurthy, U Boyett, J Kieran, M Kun, L AF Young-Poussaint, T Ramamurthy, U Boyett, J Kieran, M Kun, L TI Establishing a multi-institutional pediatric brain-tumor neuroimaging center (NIC) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 435 EP 435 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400465 ER PT J AU Zacharoulis, S Chi, S Turner, C Klement, G Lehmann, L Fox, V Semri, G Kieran, M AF Zacharoulis, S Chi, S Turner, C Klement, G Lehmann, L Fox, V Semri, G Kieran, M TI Esophageal strictures in patients with supratentorial primitive neuroectodermal tumor treated with craniospinal irradiation followed by high-dose chemotherapy SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Dana Farber Canc Inst, Bone Marrow Transplant Program & Gastroenterol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 443 EP 443 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400499 ER PT J AU Meyer, EA Tao, ML Streja, L Garvie, PA Parsons, SK AF Meyer, EA Tao, ML Streja, L Garvie, PA Parsons, SK TI Health-related quality of life of children with brain tumors: Parent report using the HUI2/3 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 447 EP 447 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400517 ER PT J AU Meyer, EA Parsons, SK Delaney, BL Chordas, CA Kieran, MW Turner, CD AF Meyer, EA Parsons, SK Delaney, BL Chordas, CA Kieran, MW Turner, CD TI Caring for survivors of childhood brain tumors: Clinical service needs from the parents' perspective SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 447 EP 447 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400516 ER PT J AU Victoria, ML Doyle, J Gambhir, R Cieurzo, C Barry, S Gannon, B AF Victoria, ML Doyle, J Gambhir, R Cieurzo, C Barry, S Gannon, B TI A school intervention program to address the learning and school adjustment needs of children treated for brain tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Dana Farber Canc Inst, Div Psychosocial Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 448 EP 448 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400520 ER PT J AU Waber, DP Chiverton, A Kieran, V Pomeroy, SL Rivkin, MJ AF Waber, DP Chiverton, A Kieran, V Pomeroy, SL Rivkin, MJ TI Neuropsychological bases of everyday cognitive problems in adolescents treated for craniopharyngioma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat NeuroOncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 448 EP 448 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400521 ER EF